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Activation of AMPK/Nrf2 signaling by Manuka honey protects human dermal fibroblasts against oxidative damage by improving antioxidant response and mitochondrial function promoting wound healing
... 3,4,7 In that sense, Manuka honey (MH), a much appreciated honey derived from the Leptospermum scoparium tree (Myrtaceae family), typical in New Zealand, eastern Australia and the Mediterranean region, has shown excellent biological activities including antibacterial, antioxidant, wound-healing and antiproliferative properties as well as a very interesting physicochemical composition. 8,9,10,11,12 However, to the best of our knowledge, there is no evidence on its neuroprotective potential. ...
... 98.5 g glucose and 119.1 g of fructose in 50 mL of de-ionized water 9 . As it can be appreciated in Fig. 6A, B, no significant differences (p < 0.05) were found between the MEtreated group and the control group, while AH addition showed the same worsening effects as MH, leading to 39.43-, 71.21-and 70.51-fold diminution of the swimming speed, wavelength, and activity, respectively, compared to the control. ...
... Despite the fact that MH is a natural product with remarkable biological properties both in vitro 8,9,11,10,36,37,38 and in vivo, 39,40 little is known about its neuroprotective potential. Considering its ability to scavenge free radicals and the implication of oxidative stress in the pathogenesis of age-related diseases such as AD, we decided to investigate the possible effects of MH in alleviating Aβ and Tau-induced toxicity in C. elegans models of AD. ...
Alzheimer's is a chronic degenerative disease of the central nervous system considered the leading cause of dementia in the world. It is characterized by two etiopathological events related to oxidative stress: the aggregation of β-amyloid peptide and the formation of neurofibrillary tangles of hyperphosphorylated Tau protein in the brain. The incidence of this disease increases with age and has been associated with inadequate lifestyles. Some natural compounds have been shown to improve the hallmarks of the disease. However, despite its potential, there is no scientific evidence about Manuka honey (MH) in this regard. In the present work we evaluated the effect of MH on the toxicity induced by Aβ aggregation and Tau in a Caenorhabditis elegans model. Our results demonstrated that MH was able to improve indicators of oxidative stress and delayed Aβ-induced paralysis in the AD model CL4176 through HSP-16.2 and SKN-1/NRF2 pathways. Nevertheless, its sugar content impaired the indicators of locomotion (an indicator of tau neurotoxicity) in both the transgenic strain BR5706 and in the wild-type N2 worms.
... On the experience of our previous reports [7][8][9][10] and the antioxidant potential of MUD1 (it presents 1435.66 ± 71.78 mg/100 g and 295.84 ± 14.80 mg/100 g of Total phenolic content and total flavonoids content, respectively) [2], in the present study we evaluated the efficacy of beeswax by-products, MUD1, as a potential therapeutic agent against oxidative damage induced by 2,2′-aszobis(2-amidinopropane) dihydrochloride (AAPH) in Human Dermal Fibroblasts (HDF). HDF are considered an excellent model system to study several aspects of cell physiology, and are widely used to evaluate the in vitro effect of substances of interest in the prevention of oxidative damage caused by different agents [8,11]. We hypothesized that if beeswax byproducts, such as the potent antioxidant MUD1, could protect HDF cells from oxidative damage induced by AAPH, they could be considered as potential therapeutic agents used to speed up wound healing in patients suffering from chronic diseases. ...
... According to our recently published results that showed that MUD1 contains high content in fiber, protein, carbohydrate, polyphenol and flavonoid, and presents antioxidant properties [2], we decided to test the efficacy of MUD1 against AAPH-induced stress in HDF cells. The measurement of intracellular ROS production represents a very useful tool for the evaluation of oxidative stress promoted by AAPH [11,12]. The accumulation of ROS can result in the hyperactivation of the inflammatory response, tissue damage, and oxidative stress phenomena [13]. ...
... AAPH-treatment significantly increased NO2 − accumulation (p < 0.05), which was efficiently counteracted by MUD1 pre-treatment, restoring also in this case, levels similar to a control group at 750 µg/mL. Similar effects were obtained when Manuka honey was used as a therapeutic agent against AAPH induced oxidative stress in HDF cells by reducing intracellular ROS production and NO2 − accumulation [11]. Also, pre-treatment with strawberry extracts have been demonstrated to counteract the oxidative damage induced by different chemical and biological agents such as hydrogen peroxide [15], ultraviolet radiations [16], and lipopolysaccharide [7,8]. ...
The antioxidant capacity and the phytochemical composition of two by-products from beeswax recycling processes were recently investigated. The aim of the present work was to evaluate the efficacy of one of these by-products, MUD1, against the oxidative stress induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) in human dermal fibroblast (HDF) cells. After a preliminary viability assay, the protective effect of MUD1 was investigated through the measurement of apoptosis level, the reactive oxygen species (ROS) and nitrite (NO2−) production, the level of protein and lipid biomarkers (carbonyl groups, total glutathione and thiobarbituric acid-reactive substance) of oxidative damage, and the measurement of antioxidant enzymes activities (glutatione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase and catalase). The obtained results showed that MUD1 exerted protective effects on HDF, increasing cell viability and counteracted the oxidative stress promoted by AAPH-treatment, and improved mitochondria functionality and wound healing capacities. This work shows the antioxidant effects exerted by beeswax by-products, demonstrating for the first time their potential against oxidative stress in human dermal fibroblast cells; however, further research will be necessary to evaluate their potentiality for human health by more deeply in vitro and in vivo studies.
... Manuka honey (MH), obtained from the nectar of honey bees (Apismellifera), comes from New Zealand Manuka tree (Leptospermum scoparium, Family: Myrtaceae) and has been largely studied for its health beneficial effects ( Alvarez-Suarez et al., 2014). It is a complex mixture of various pharmacological and biologically active compounds ( Alvarez-Suarez et al., 2016;Afrin et al., 2017Afrin et al., , 2018a) and those compounds are thought to be involved in its anti-microbial ( AlvarezSuarez et al., 2014), wound healing, anti-oxidative ( Alvarez-Suarez et al., 2016) and chemopreventive effects ( Afrin et al., 2018aAfrin et al., , 2018b), but the anti-inflammatory properties remain to be unclear in spite of its high nutritional values. ...
... Manuka honey (MH), obtained from the nectar of honey bees (Apismellifera), comes from New Zealand Manuka tree (Leptospermum scoparium, Family: Myrtaceae) and has been largely studied for its health beneficial effects ( Alvarez-Suarez et al., 2014). It is a complex mixture of various pharmacological and biologically active compounds ( Alvarez-Suarez et al., 2016;Afrin et al., 2017Afrin et al., , 2018a) and those compounds are thought to be involved in its anti-microbial ( AlvarezSuarez et al., 2014), wound healing, anti-oxidative ( Alvarez-Suarez et al., 2016) and chemopreventive effects ( Afrin et al., 2018aAfrin et al., , 2018b), but the anti-inflammatory properties remain to be unclear in spite of its high nutritional values. ...
... After the in- cubation of LPS, the levels of lipid (1.85 fold) and protein (1.48 fold) damage were significantly higher compared to control group (Fig. 2b and c), while MH treatment significantly (p < 0.05) protected lipid and protein damage in LPS stressed cells by decreasing TBARS and protein carbonyl content up to 1.21 fold and 1.12 fold (Fig. 2b and c). In agreement with our results, MH has also shown a significant reduction of TBARS levels and protein carbonyl content triggered by AAPH in HDF cells ( Alvarez-Suarez et al., 2016). Moreover, polyphenol-con- taining food demonstrated similar effects by reducing LPS-induced overproduction of TBARS and protein carbonyl content in RAW 264.7 macrophages ( Gasparrini et al., 2017). ...
The redox-system is altered by oxidative stress that is initiated by oxidative agents such as lipopolysaccharides (LPS) and reactive oxygen species (ROS), which are strongly involved in chronic inflammation. Even if Manuka honey (MH) is a good source of polyphenol rich antioxidants, its antioxidant and anti-inflammatory effects are still elusive. The aim of the present work was to explore the protective effects of MH against E.coli LPS stimulated oxidative stress and inflammatory condition and the underlying mechanisms on murine RAW 264.7 macrophages. Pre-treatment with MH markedly inhibited LPS induced ROS and nitrite accumulation and increased the protection against cellular biomolecules such as lipids, proteins, and DNA. Stimulation by LPS suppressed both antioxidant enzyme activities and expressions, and Keap1-Nrf2 signaling pathway which was significantly (p < 0.05) increased in the presence of MH. The pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, and other inflammatory mediators (iNOS) were enhanced after LPS treatment, whereas MH suppressed the expression of these inflammatory markers. Moreover, MH also inhibited the expression of TLR4/NF-кB via IкB phosphorylation in LPS-stressed RAW 264.7 macrophages. In conclusion, MH acted as a natural agent for preventing oxidative and inflammatory-related diseases.
... Manuka honey (MH) is increasingly treasured for its diverse poly- phenol and antioxidant properties, since it is already known for its wound healing and anti-microbial effects [9][10][11]. The chemopreventive role of this honey on human colon cancer cells has already been eval- uated in our previous reports focusing on different molecular aspects such as anti-proliferation, cell cycle obstruction, apoptosis activation, induction of oxidative stress, disruption of cell metabolism and anti- metastatic observation [10,12,13]. ...
... The number of live and dead cells decreased in each treat- ment and a similar trend was also observed when combined treatment was used in both cell lines (Fig. 4). At the same time, in non-cancer cells, MH also had the ability to decrease stress inducing apoptotic ef- fects [9]. ...
... Similarly, the migration ability of HCT-116 and LoVo cells decreased by 60% and 57% after 5-FU treat- ment, while in the presence of MH the inhibitory activity of 5-FU in- creased by 64% in HCT-116 cells (Fig. 8C) and 68% for LoVo compared to control (Fig. 8D). On the contrary, MH promoted the migration ability in non-cancer cells due to the enhancement of wound healing activities [9]. ...
The development of chemo-sensitizers is urgently needed to overcome 5-fluorouracil (5-FU) therapeutic resistance and adverse toxicity in colorectal cancer. This work aims to evaluate the synergic effects of 5-FU and Manuka honey (MH), a rich source of bioactive compounds, in enhancing the anticancer effects of this drug on human colon cancer HCT-116 and LoVo cells. Compared to 5-FU alone, MH synergistically enhanced the chemotherapeutic effects of 5-FU, by reducing cell proliferation through the suppression of EGFR, HER2, p-Akt and p-mTOR expression, and promoting apoptosis by the modulation pro-apoptotic (p53, Bax, Cyto c, FasL caspase-3, -8, -9 and cleave-PARP) and anti-apoptotic (Bcl-2) markers. The activations of p-p38MAPK and p-Erk1/2 pathways and ROS production were also involved in this process. Downregulation of transcription factor (NF-κB and Nrf2) and antioxidant enzyme activity (SOD, catalase, glutathione peroxidase and glutathione reductase) and expression (SOD, catalase and HO-1) were more evident after the combined treatment, leading to more cell death by oxidative stress. Moreover, additive effects were also observed by increasing lipid and protein oxidation and arresting cell cycle. All the parameters of mitochondrial respiration and glycolysis function decreased and both cells entered the quiescent stage after the combined treatments. MH also influenced the anti-metastasis effects of 5-FU by decreasing migration ability, suppressing the expression of MMP-2, MMP-9 and increasing N-cadherin and E-cadherin. In conclusion, MH could be a useful preventive or adjuvant agent in the treatment of colorectal cancer with 5-FU.
... Manuka has attracted a lot of attention as a strong antimicrobial and antioxidative agent (Alvarez- Suarez et al., 2016;Alvarez-Suarez et al., 2014;Bogdanov et al., 2008;Carter et al., 2016) as well as for its wound healing ability (Bischofberger et al., 2016;Tan et al., 2009). Potential antigenotoxic activities have been reported in an in vivo experimental model, exerting a protective role against oxidative damage, reducing DNA damage, reducing malondialdehyde levels, and glutathione per- oxidase activity ( Jubri et al., 2013). ...
... Potential antigenotoxic activities have been reported in an in vivo experimental model, exerting a protective role against oxidative damage, reducing DNA damage, reducing malondialdehyde levels, and glutathione per- oxidase activity ( Jubri et al., 2013). Induction of a wound healing mechanism in dermal fibroblasts can be explained due to the im- provement of the antioxidant response, i.e. by modulating the AMPK/ Nrf2 signaling pathway, encasement of superoxide dismutase and cat- alase activity in cells exposed to (MH) ( Alvarez-Suarez et al., 2016). It is hypothesized that its antioxidant properties are due to its numerous polyphenolic composition. ...
... It was shown by Almasaudi et al., (2016) that the administration of MH was protective in the treatment of acetic acid- induced chronic gastric ulcers in rats against oxidative stress by in- creasing the enzymatic (GPx and SOD) and nonenzymatic (GSH) anti- oxidants, showing an inducible effect on their activities. Also, MH promoted the expression of antioxidant enzymes SOD and CAT in the human dermal fibroblasts against oxidative damage ( Alvarez-Suarez et al., 2016). Supplementation with MH reduced oxidative damage in young and middle rats, possibly through the modulation of its anti- oxidant enzyme activities and its high total phenolic content ( Jubri et al., 2013). ...
Manuka honey has been widely researched regarding its biological properties, in particular its antimicrobial and antioxidant capacities. We tested the genotoxic and genoprotective properties of Manuka honey, ranging from 25-1000 μg/mL, by performing an in vitro comet assay after exposure to human whole blood. No genotoxic effect on whole blood cells was observed within the tested concentration range (p = 0.154). Then, the antigenotoxic potency of Manuka honey against oxidative DNA damage to whole blood cells was assessed. Prior to Manuka honey treatment a modest decrease of H2O2-induced DNA damage was detected in cells, with no statistical significance (p = 0.087). Post-treatment, Manuka honey displayed a stronger potential to attenuate damaged cells at all tested concentrations, with a statistical significant difference (p < 0.001), where concentrations of 25 and 100 μg/mL were most efficient. Manuka honey exhibited a marked potential to protect DNA of whole blood cells from oxidative damage induced by hydrogen peroxide in vitro.
... 11,12 Honey is a good source of natural therapeutic molecules with antibacterial, wound healing, antioxidant, anti-inflammatory, and anticancer properties. [13][14][15] Manuka honey (MH) is a particular type of honey collected from the Leptospermum scoparium tree (Family: Myrtaceae), which has been widely investigated for its antioxidant, antibacterial and wound-healing activities as well as for its physiochemical properties and attractive biological and pharmacological compounds. 13,14 However, there has been a sporadic effort on the anticancer activity of whole honey on human colon cancer in vitro 15 and only two investigations have reported the antiproliferative effect of MH on colon cancer cells. ...
... [13][14][15] Manuka honey (MH) is a particular type of honey collected from the Leptospermum scoparium tree (Family: Myrtaceae), which has been widely investigated for its antioxidant, antibacterial and wound-healing activities as well as for its physiochemical properties and attractive biological and pharmacological compounds. 13,14 However, there has been a sporadic effort on the anticancer activity of whole honey on human colon cancer in vitro 15 and only two investigations have reported the antiproliferative effect of MH on colon cancer cells. 16,17 The present study was designed to characterize the anti-proliferative and apoptotic activities of MH in human colon adenocarcinoma cells (HCT-116) and Dukes' type C, grade IV, colon metastasis cells (LoVo). ...
... Apoptotic cells were identified using the Tali™ Apoptosis Assay Kit-Annexin V Alexa Fluor ® 488 (Invitrogen™, Life Techonoliges, Milan, Italy) as reported earlier. 14 Cells were seeded at a density of 1.5 × 10 5 cells per well into 6 wells and treated for 48 h with the MH (0, 10, 15 and 20 mg mL −1 for HCT-116 cells and 0, 30, 40 and 50 mg mL −1 for LoVo cells). Cells were harvested 48 h post-treatment and centrifuged for 15 min at 1500 rpm at 4°C. ...
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid. The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to different concentration of MH (0-20 mg/mL for HCT-116 cells and 0-60 mg/mL for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as apoptosis and cell cycle regulatory gene and protein expression. MH exhibited profound inhibitory effects on cellular growth by reducing the proliferation ability, inducing apoptosis and arresting cell cycle in a dose-dependent manner. Interestingly, MH treatment in non-malignant cells did not exert any significant toxicity at similar concentration. The apoptosis event was associated with increasing expression of p53, cleaved-PARP and caspase-3, and with the activation of both intrinsic (caspase-9) and extrinsic (caspase-8) apoptotic pathways. MH induced cell cycle arrest at S phase in HCT-116 cells, simultaneously, in LoVo cells, it arrested at G2/M phase through the modulation of cell cycle regulator genes (cyclin D1, cyclin E, CDK2, CDK4, p21, p27 and Rb). The expression of p-Akt was suppressed while the expression of p-p38MAPK, p-Erk1/2 and endoplasmic stress markers (ATF6 and XBP1) was increased for apoptosis induction. Overall, these findings indicate that MH could be a promising preventive or curative food therapy for colon cancer.
... At present, natural com- pounds are streamlined because of their potential toxicity to cancer cells and because they are less or non-toxic to non- cancer cells. 7,17 The bioactive components of Manuka honey (MH) are thought to be accountable for its anti-microbial and wound- healing capacities 18,19 , but its chemopreventive properties remain to be determined in spite of its high phenolic com- pounds. 20,21 In order to investigate whether the use of MH could be useful for the treatment and/or prevention of colon cancer, we evaluated the effect of MH on ROS, oxidative stress biomarkers (lipid, protein and DNA), antioxidant enzyme activity and expression, as well as oxidative phosphorylation (OXPHOS) and glycolysis in human colon adenocarcinoma cells (HCT-116) and Dukes' type C, grade IV, colon metastasis (LoVo) cells. ...
... Interestingly, in a previous study from our group, we observed that MH has the ability to protect healthy non-cancer cells from oxidative stress by decreasing ROS generation and increasing lipid and protein damage. 19 These findings suggest that the anti-proliferative effect of MH is associated with the oxidative stress-induced damage of human colon cancer HCT-116 and LoVo cells. ...
... 6,7,28,29 Moreover, in non-malignant cells, MH treatment increases the antioxidant enzyme activity (SOD and catalase) and expressions (Nrf2, SOD and catalase) to combat oxidative stress-induced damage. 19 These findings highlight that MH treatment decreases the antioxidant enzyme activity and expression which further elevates ROS generation. ...
Despite its high content of phenolic compounds, the chemopreventive activity of Manuka honey (MH) is still elusive. The aim of the present work was to evaluate the effects of MH on oxidative stress, antioxidant enzyme, cellular metabolism and metastatic ability in HCT-116 and LoVo cells, paying particular attention to the molecular mechanisms involved. We observed a strong induction of oxidative stress after MH treatment since it augmented the accumulation of reactive oxygen species and increased the damage to proteins, lipids and DNA. Furthermore, MH suppressed the Nrf2 dependent antioxidant enzyme expression (superoxide dismutase (SOD), catalase and heme oxygenase-1) and the activity of SOD, catalase, glutathione peroxidase and glutathione reductase. Cell metabolisms were markedly disrupted after MH treatment. It decreased maximal oxygen consumption and spare respiratory capacity, which could reduce mitochondrial function that is correlated with cell survival potential. Simultaneously, MH decreased the extracellular acidification rate (glycolysis) of HCT-116 and LoVo cells. Furthermore, MH suppressed the p-AMPK/AMPK, PGC1α and SIRT1 activation, involved in the survival of HCT-116 and LoVo cells under metabolic stress conditions. Dose-dependently, MH reduced the migration and invasion (MMP-2 and MMP-9) ability, concurrently regulated EMT related markers (E cadherin, N cadherin, and β-catenin) in both cell types. The above finding indicates that MH induces HCT-116 and LoVo cell death partly by enhancing oxidative stress, as well as by regulating the energy metabolism in both aerobic and anaerobic pathways and suppressing metastasis ability.
... These include cardioprotective (129), hepatoprotective (131,132), hypoglycemia (133,134), reproductive (139,140), and antihypertensive effects (121,142). Other effects such as antibacterial (142)(143)(144), antifungal (145,146), antiviral (147), anti-inflammatory (148)(149)(150), and antitumor (119,(151)(152)(153)(154)(155) have also been documented and attributed to honey. ...
... Some reports have established a correlation between floral origins and phenolic compounds and flavonoids (179,(182)(183)(184). Correspondingly, a correlation between total phenolic content in honey and its antioxidant activity has been demonstrated (169,180). Other studies have also demonstrated that honey is able to increase plasma antioxidants and ameliorate oxidative stress in tissues (121,133,134,137,138,149,(185)(186)(187)(188). ...
This paper reviews the potential role of honey as a therapeutic antioxidant to reduce oxidative stress and improve cognitive ageing. All articles indexed to PubMed Central (PMC) were searched using the following key words: honey, antioxidant, memory and ageing. Honey is a natural insect-derived product with therapeutic, medicinal and nutritional values. Antioxidant properties of honey quench biologically-circulating reactive oxygen species (ROS) and counter oxidative stress while restoring the cellular antioxidant defense system. Antioxidant properties of honey may complement its nootropic effects to reduce cognitive ageing.
... It has been reported previously that Manuka honey has the ability to improve the antioxidant response in HDFa cells exposed to oxidative stress by activating AMPK phosphorylation and antioxidant response elements (ARE) response in mitochondria of HDFa (78). Therefore, the ability of Manuka honey to promote wound healing could be due to its antioxidant properties and also as reported previously by activating AMPK phosphorylation and ARE, which improve the antioxidant response of HDFa (79). ...
... The seventh experiments was undertaken to determine the relative ROS levels in HDFa at passage 22 (older cells). In the present study, results ( Nrf2 through AMPK phosphorylation (78). However, the activation of Nrf2 pathway leads to an increase in the antioxidant enzymes expression. ...
Impaired wound healing can cause life threatening effects to patients. Reactive oxygen species (ROS) play a significant role in wound healing through regulating disinfection, angiogenesis, proliferation and migration. However, excess ROS causes oxidative stress, leading to apoptosis of surrounding cells such as fibroblasts. The control of ROS level is essential for successful wound healing. There has been increasing interest in naturally-derived alternatives for treatment of impaired wound healing. Honey has been an integral part of herbal medicine throughout history. Manuka honey is a widely used medicinal honey with anti-bacterial, anti-oxidant and anti-inflammatory properties. However, the effect of Manuka honey on ROS is not fully understood. Human dermal fibroblasts (HDFa) of two ages (passage 5 and 22) were treated with or without Manuka honey, sugar solution, H2O2 and vitamin C. Cell viability was measured by Cell Titer-Blue® Viability Assay. Manuka honey was not deleterious to the cell viability up to 2% (w/v). This study found that flow cytometry was more reliable than the fluorimetry method. The ROS levels in HDFa cells at passage 5 significantly decreased following incubation with vitamin C (p<0.001) and 1% w/v Manuka honey (P<0.05) compared with untreated cells. Also, the level of ROS in HDFa cells at passage 22 were significantly reduced with vitamin C (p=0.0009) and with all concentration of Manuka honey studied (0.15%, 0.5% and 1% w/v, p<0.001). In conclusion, Manuka honey showed anti-oxidants properties in vitro in fibroblast cells, that appears to be through reduction of ROS. Further work is required to confirm this finding and to determine how these effects may mediate anti-oxidants benefits in a clinical context.
... Flavonoids within the honey scavenge free oxygen radicals, reducing inflammation and minimizing tissue damage [7][8][9]. Previous work by Alvarez-Suarez et al. has analyzed the phenolic content of Manuka honey via HPLC-MS, and it is theorized that these components improve the intracellular antioxidant response [10]. In addition, honey's hydrogen peroxide content acts as an antiseptic against many types of bacteria [11][12][13]. ...
... Sell The mechanisms through which Manuka honey affects the dHL-60 neutrophil model are unknown and possibly involve a combination of processes initiated by different Manuka honey components. Alvarez-Suarez et al. have theorized that polyphenolic components of the honey, such as pinocembrin or pinobanksin, cross the cellular membrane to scavenge intracellular free radicals and trigger 5' AMP-activated protein kinase (AMPK) phosphorylation, increasing antioxidant enzyme expression [10]. Evidence gathered by Gasparrini et al. demonstrates that Manuka honey increases the intracellular expression of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and glutathione s-transferase in macrophages, supporting the Alvarez-Suarez theory [61]. ...
Recent work has shown that Manuka honey, an increasingly popular wound additive with potent antibacterial properties, also has anti-inflammatory properties. However, little research has been done examining its effect on neutrophils. This study investigates the hypothesis that Manuka honey reduces neutrophil superoxide release and chemotaxis and reduces the activation of the inflammatory nuclear factor- κ B (NF- κ B) signaling pathway under honey’s cytotoxic limit. A differentiated HL-60 cell line was used as a neutrophil model and cultured in various concentrations of Manuka honey for 3 and 24 hours to measure cytotoxicity via mitochondrial activity and visual trypan-exclusion count. Cytochrome C and Boyden chamber assays were used to measure the effect of Manuka honey on superoxide release and chemotaxis toward fMLP, respectively. Additionally, a Western blot for NF- κ B inhibitor α (I κ B α ) was performed to measure Manuka honey’s effect on the NF- κ B pathway via I κ B α phosphorylation. The results indicate a cytotoxic limit of 3-5% v/v. The presence of 1% honey decreased superoxide release at 24 hours. The 0.5, 1, and 3% honey concentrations reduced chemotaxis and I κ B α phosphorylation in a dose-dependent fashion. These results suggest that Manuka honey significantly reduces neutrophil recruitment and inflammatory behavior in the wound site in a dose-dependent fashion under the cytotoxic limit.
... Honey has been used to prevent, and treat patients with, oral mucositis resulting from radio/chemotherapy [5,6], to reduce esophagitis induced by chemoradiation therapy during the treatment of lung cancer [7], to treat skin ulcer [8,9] and to treat acute irritating cough [10]. Also, due to the recognized antibacterial activity of honey [11][12][13][14] its potential application in wound healing and tissue engineering has been studied [15,16], as for example for the treatment of burns and skin disorders [12,17]. Indeed, over the centuries, honey has been an essential ingredient in traditional medicines around the world [1]. ...
... (i) Verifying honey authenticity, through the identification of botanical, entomological and/or geographical origin [2,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. (ii) Evaluating honey physicochemical parameters as well as antioxidant and antimicrobial activities and therapeutic properties [4,11,[13][14][15]22,23,25,28,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. (iii) Detecting insecticides, pesticides, veterinary drug or multi-class antibiotic residues in honey [54][55][56][57]. ...
Honey-rich composition in biologically active compounds makes honey a food products highly appreciated due to the nutritional and healthy properties. Food-manufacturing is very prone to different types of adulterations and fraudulent labelling making it urgent to establish accurate, fast and cost-effective analytical techniques for honey assessment. In addition to the classical techniques (e.g., physicochemical analysis, microscopy, chromatography, immunoassay, DNA metabarcoding, spectroscopy), electrochemical based-sensor devices have arisen as reliable and green techniques for food analysis including honey evaluation, allowing in-situ and on-line assessment, being a user-friendly procedure not requiring high technical expertise. In this work, the use of electronic tongues, also known as taste sensor devices, for honey authenticity and assessment is reviewed. Also, the versatility of electronic tongues to qualitative (e.g., botanical and/or geographical origin assessment as well as detection of adulteration) and quantitative (e.g., assessment of adulterants levels, determination of flavonoids levels or antibiotics and insecticides residues, flavonoids) honey analysis is shown. The review is mainly focused on the research outputs reported during the last decade aiming to demonstrate the potentialities of potentiometric and voltammetric multi-sensor devices, pointing out their main advantages and present and future challenges for becoming a practical quality analytical tool at industrial and commercial levels.
... From a chemical point of view, honey is considered a supersaturated solution of sugars, with fructose (38%) and glucose (31%) being the two most abundant components. Other minor compounds have also been associated with honey's biological properties, such as polyphenols, enzymes, free amino acids, proteins, minerals, and vitamins [1]. ...
... ChA = [(A0 − A1)/A0] × 100 (1) in which A0 was the absorbance of the control and A1 the absorbance of each honey sample. The O2 •− scavenging activity of honey was investigated using a modified nitrite method that was based on the ability of the O2 •− generated by hypoxanhine/xanthine oxidase (HX/XO) to oxidize hydroxylamine to nitrite ion at pH 8.2 [51]. ...
Three types of monofloral honey from the Andean regions of Ecuador (Avocado, Eucalyptus and Rapeseed honey) were analyzed to determine their floral origin, physicochemical parameters, chemical composition, antioxidant capacity and their capacity to reduce in vitro bacterial biofilms. The chemical composition varied considerably depending on floral origin. The highest values of bioactive compounds were found in Avocado honey, classified as dark amber in color, while the lowest values were found in Eucalyptus honey followed by Rapeseed honey, both classified as extra light amber. Compared to Eucalyptus and Rapeseed honey, Avocado honey showed a more effective superoxide scavenging activity, chelating metal ions capacity, and a higher ability to protect human erythrocyte membranes against lipid peroxidation. For antimicrobial activity, the hydrogen peroxide content and the capacity to inhibit the biofilm formation and to remove preformed biofilm from Staphylococcus aureus and Klebsiella pneumoniae was determined. Avocado honey showed the highest values of hydrogen peroxide content, as well as the highest capacity to reduce in vitro bacterial biofilms. A correlation between color vs phenolics content vs superoxide scavenging activity vs chelating metal ions capacity and the capacity to protect human erythrocyte membranes against lipid peroxidation was found.
... Moreover, honey demonstrates strong antioxidant action, reducing the consequences of oxidative reactions and the production of reactive oxygen species and free radicals [6]. The strong antibacterial properties of honey are attributed to its high osmolarity due to elevated sugar concentrations [11] and rather low pH owing to the high content of organic acids [12]. ...
The current study aimed to assess the effect of thyme honey on pain relief in patients with minor aphthous ulcers as a primary objective, its healing effect on ulcer size reduction, and the Oral Health Impact Profile (OHIP‐14). In this randomized clinical trial, 30 patients (15 in each group) having minor aphthous ulcers at the oral diagnostic clinic at the British University in Egypt were treated with either thyme honey or triamcinolone acetonide in orabase. Different clinical parameters were recorded for both groups at various intervals, such as pain intensity using the Visual Analog Scale (VAS), size of ulcers in mm, and OHIP‐14. Thyme honey intervention showed more significant ulcer size reduction than the triamcinolone acetonide group on days 5, and 7, and a more substantial decrease in pain intensity on days 3, 5, and 7. Additionally, the thyme honey group showed significantly lower OHIP values than the triamcinolone acetonide group after 7 days. The current clinical trial furnished evidence of the effectiveness of thyme honey in managing minor aphthous ulcers for the first time and revealed clinical efficiency with satisfactory patient outcomes.
... The antibody-reactive bands were visualized by enhanced chemiluminescence reagents. The band densities were calculated with UV Band software (Alvarez-Suarez et al., 2016;Raeiszadeh et al., 2018). ...
... Studies have shown that polysaccharides, flavonoids, polyphenols, alkaloids, terpenes, natural pigments, plant volatile oils, quinones, and other natural chemicals have anti-inflammatory properties [14,15]. In addition, fruit polyphenols have been recommended as complementary treatments due to their ability to reduce the production of critical free radical signaling molecules such as ROS and NO [16][17][18][19][20]. In recent years, numerous in vitro and in vivo studies have shown the important effects of OLEU on inflammatory responses, which investigate its possible role in inhibiting the production of pro-inflammatory cytokines such as IL-1β and IL6 [16,18,21,22]. ...
Oleuropein (OLEU) is the most prevalent phenolic component in olive varieties, and it has been considered for its powerful antioxidant properties in therapeutic applications. OLEU has anti-inflammatory properties and performs this property by suppressing inflammatory cells' function and reducing oxidative stress caused by various factors. This study investigated the ability of OLEU to polarize LPS-stimulated murine macrophage (MQ) cell RAW 264.7 into M1/M2 macrophages. As a first step, the cytotoxicity effects of OLEU were evaluated on LPS-stimulated RAW 264.7 cells using the thiazolyl blue (MTT) colorimetric test. Then, cytokines production, gene expression (Real-Time PCR), and functions (Nitrite oxide assay and phagocytosis assay) of OLEU-treated LPS-stimulated RAW 264.7 cells were evaluated. Our findings demonstrated that OLEU could reduce nitrite oxide (NO) production in LPS-stimulated RAW 264.7 cells by downregulating the inducible nitric oxide synthase gene expression. Furthermore, OLEU therapy decreases the expression of M1-associated pro-inflammatory cytokines production (IL-12, IFN-γ, and TNF-α) and genes expression (iNOS, TNF-α) while increasing the M2-associated anti-inflammatory gene expression and cytokines production (IL-10, and TGF-β). Based on the result, OLEU may be considered a potential therapeutic approach for inflammatory diseases due to its possible effects on oxidative stress-related factors, cytokine expression and production, and phagocytosis.
... 11 Manuka honey is a typical example of medical-grade honey and has attracted extensive attention and research. In addition to its well-known antibacterial activity, numerous in vitro [49][50][51][52][53][54][55] and in vivo 54,56-59 studies have confirmed its anti-inflammatory and antioxidant properties. These studies have shown that manuka honey can inhibit the respiratory burst of neutrophils and the formation of reactive oxygen species, improve oxidative stress by activating the signalling pathway 5'-adenosine monophosphate-activated protein kinase/5'-phosphorylated adenosine monophosphate-activated protein kinase/nuclear factor erythroid-2-related factor-2, and increase enzymatic (catalase, glutathione peroxidase, and superoxide dismutase) and non-enzymatic (glutathione) activities. ...
Dry eye has become an increasingly prevalent public health issue for which there is currently no cure. Manuka honey possesses anti-inflammatory and antioxidant properties that can be used to treat dry eye. The present study aimed to systematically review evidence supporting the treatment of dry eye with manuka honey and quantify this evidence via meta-analysis. Randomised clinical trials that fulfilled the inclusion criteria from database inception until 5 September 2021, were identified through online searches of seven databases, including but not limited to Embase, Medline, and Central. Changes between the point of longest follow-up and baseline subjective symptoms, tear film quality, ocular surface characteristics, adverse events, and compliance were selected for meta-analysis. A total of 288 adult participants with dry eye from five eligible randomised controlled trials were analysed. Compared with the control groups, treatment with manuka honey demonstrated a significant improvement in Ocular Surface Disease Index, Standard Patient Evaluation of Eye Dryness, tear evaporation rate, negative conversion rate of matrix metalloproteinase-9 levels, ocular surface staining, and daily use frequency of lubricant. No serious adverse events were reported, except for temporary stinging and redness, which were generally tolerated. This review found that manuka honey demonstrated promising results for the treatment of dry eye. However, limitations of the included studies and analytical methodology affect the reliability of this conclusion. Therefore, further high-quality randomised clinical trials are required to confirm the efficacy and safety of the use of manuka honey in the treatment of dry eye.
... Under normal conditions, Nrf2 is bound to its suppressor Keap1 and is located in the cytoplasm. However, under oxidative stress, the cysteine residue modification of Keap1 separated Nrf2 from Keap1 and transferred it into the nucleus, and combined with ARE in the promoter of genes encoding antioxidant enzymes (including HO-1) to counteract cellular oxidative stress (Alvarez-Suarez et al., 2016). HO-1 is a downstream mediator of Nrf2, which catalyze the degradation of heme into biliverdin, iron and carbon monoxide have antioxidant and anti-inflammatory effects (Gabunia et al., 2012). ...
Jujube has great potential as food and traditional drugs in several countries. To study the anti-inflammatory influence of jujube peel polyphenols in lipopolysaccharide (LPS) induced RAW 264.7 cells through mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB) and nuclear erythroid 2-related factor 2 (Nrf2) signaling pathways. In this study, the phenolic composition of polyphenols in jujube peel was analyzed using LC-MS/MS, and which was confirmed that the main polyphenols were p-coumaric acid, catechin and rutin. Meanwhile, jujube peel polyphenols attenuated the generation of TNF-α, IL-1β, IL-6, NO and PGE2 by inhibiting MAPK and NF-κB signaling pathways. Additionally, jujube peel polyphenol activate Nrf2 from the cytoplasm to the nucleus, regulate antioxidant enzymes and pro-inflammatory cytokines, and reduce oxidative stress and inflammatory responses. Results obtained from this study suggest that jujube peel polyphenols may alleviate oxidative stress and inflammation by inhibiting MAPK and NF-κB and activating Nrf2 signaling pathways. Furthermore, jujube peel polyphenols have a synergistic effect in the treatment of LPS-induced inflammatory in RAW 264.7 cells. In conclusion, this study not only reveals the mechanism by which jujube peel polyphenols inhibit LPS-induced inflammation in RAW 264.7 cells, but also provides guidance for the development of new anti-inflammatory drugs.
... [19][20][21] Interestingly, honey and its polyphenolic contents have been reported to possess antioxidant, antiinflammatory, antimicrobial and anti-cancer activities. [22][23][24][25][26][27] Most importantly, it is also now well documented that the glucose induced induction of COX-2 or PGE 2 mediated inflammatory activity in human islets suggested one of the major routes through which hyperglycemia contributes to the destruction of pancreatic beta cells. 28 In view of these, we hypothesized that the polyphenolic fraction of honey inhibits the glucose-induced COX-2 or PGE 2 mediated inflammatory activities by regulating the expression of microRNAs in pancreas, the main organ affected by hyperglycemia. ...
Objectives
Honey total polyphenolic fraction (HTPF) is reported to have anti-disease potential, however the role of HTPF in the regulation of microRNAs (miRNAs) has never been investigated. This study was undertaken to investigate the potential of HTPF against inflammation via regulation of miRNAs in pancreatic islets of Langerhans.
Methods
Pancreatic islets were isolated from C57BL/6 mice and HTPF was purified from honey. Bioinformatics algorithms were used to determine miRNA target genes. Expression of miRNA and mRNA was determined using their specific taqman assays. Pairing between miRNA and 3 ′ untranslated region (3 ′ UTR) of mRNA was confirmed using luciferase reporter clone containing the 3 ′ UTR of mRNA sequences and results were verified by transfection of mouse pancreatic β-cell line Min6 with miRNA inhibitors.
Results
The data showed that mmu-miR-26a-5p is a direct regulator of cyclooxygenase-2 (COX-2) expression and HTPF inhibits COX-2 expression or prostaglandin E 2 (PGE 2 ) production via up-regulating mmu-miR-26a-5p expression. Transfection of islets with anti-miR-26a-5p significantly enhanced COX-2 expression and PGE 2 production ( p < .01), while HTPF treatment significantly inhibited anti-miR-26a-5p transfection-induced COX-2 expression or PGE 2 production ( p < .05). These findings were further verified in pancreatic β-cells Min6. Moreover, the data also determined that HTPF also inhibits glucose-induced nuclear transcription factor (NF)-κB activity.
Conclusion
HTPF suppresses glucose-induced PGE 2 production and activation of NF-κB via negative regulation of COX-2 and mmu-miR26a-5p. These novel pharmacological actions of HTPF on glucose-stimulated pancreatic islets provide new suggestions that HTPF or HTPF-derived compounds inhibit glucose induced inflammation in pancreas by up-regulating the expression of microRNAs.
... These benefits of honey have been reported to be related to its antioxidant, antibacterial 4 , antifungal 5 , antiviral 6 , antitumor 7 , anti-inflammatory 8 , antidiabetic 9 , immunomodulatory 10 , etc. ability. Existing literary evidence suggests that honey is capable of protecting different body organs such as the brain, liver and kidneys from damage by acting as an antioxidant or enhancing cellular antioxidant defence systems [11][12][13] . It has also been demonstrated that honey plays a significant role in attenuating oxidative stress-induced cell death 14 . ...
This research sought to verify the effect of natural honey on brain levels of malondialdehyde (MDA) and reduced glutathione (GSH) in rats. Forty nine male and female Wistar rats were used for the experiment. The rats were allotted into seven groups of seven rats in each group. For one month, rats in groups 1-4 were fed with 100% feed, 20%, 30% and 40% honey respectively. The remaining 3 groups were fed with amounts of refined fructose and glucose equivalent to those in 20%, 30% and 40% honey. The brains were then excised, homogenized and used for biochemical analysis. Results showed that honey in all concentrations caused a significant increase in GSH levels but only 20% honey caused a significant decrease in MDA level when compared with control. Also, fructose feeding at 20%, 30% and 40% increased both brain GSH and MDA levels. Consequently, the influence of GSH as an antioxidant against brain lipid peroxidation needs further studies for better understanding since an increase in GSH for fructose- and honey-fed rats did not cause a simultaneous decrease in MDA content.
... Berry fruits, such as cranberries, bilberries, lowbush blueberries, and blueberries, are rich sources of bioactive compounds, mostly polyphenolics, as well as polysaccharides, carotenoids, ascorbic acid, and others (Gramza-Michałowska et al., 2017). Numerous healthpromoting properties of berries have been identified, such as in reduction of cancer, cardiovascular and neurological diseases as well as anti-inflammatory, antibacterial, antiallergic, anti-hypertensive, antiviral and wound-healing effects (Ballesteros et al., 2017;Alvarez-Suarez et al., 2016). Phenolic compounds, present in many fruits and vegetables, have been studied extensively for their high antioxidant power because they are capable of increasing resistance to oxidative damage caused by free radicals generated in the human body (Ho et al., 2020). ...
Cranberries and blueberries are small fruits known for their antioxidant properties. However, due to their high water content and short shelf life, they are generally marketed as dehydrated berries. The present work aimed to model the rehydration of dehydrated berries. Rehydration tests were conducted at 7 and 29°C using milk as a solvent and at 7, 29, and 45°C when the solvent was water. The mass gain was assessed at different intervals, and the experimental data were fitted to the Fick model considering the berries as spheres. Six empirical/semi-empirical models describing the diffusion of water during drying were used to predict the rehydration process. Fick’s law satisfactorily represented the data, and the highest diffusion coefficients were found when the berries were rehydrated in water at 45°C. Rehydration of berries in milk resulted in nutrient gain as different diffusive flows occurred during the process. The use of empirical models to predict the operating time of the rehydration processes allows flexibility as such models are mathematically simpler than the Fick model. Diffusivity is essential for the design/construction of equipment, and/or process optimization and implementation.
KEYWORDS
Blueberry; cranberry; diffusivity; mathematical modeling; Vaccinium sp
... Lavandin is known for neuronal depressive properties [26]. This could be responsible for a manuka honey were the subject of numerous in vitro studies [27] [28] [29]. N-acetylcysteine was reported to have wound healing properties comparable to dexpanthenol [30]. ...
A 30-year-old, intact female Indian rhinoceros (Rhinocerus unicornis) was presented with ongoing erosive, ulcerative skin lesions over a 4-year-period. The lesions appeared to be non-pruritic and non-seasonal. A systemic antibiotic therapy had been unsuccessful. The dermatological examination showed 8 diffusely demarcated areas of erosion, focal ulceration, mild crusting, and moderate erythema ranging from 8 to 20 cm in diameter, bilaterally on the lateral edges of the torso armor plates. The patient had no other clinical abnormalities. Coccoid and rod-shaped bacteria were identified on cytology and a bacterial culture revealed Escherichia coli spp., Staphylococcus dysgalacticae, Stenotrophomonas maltophilia, Corynebacterium spp. and Micrococus spp. A topical product line containing essential fatty acids and plant extracts was administered daily, using a spot-on, spray and balm. Within 3 weeks a substantial alleviation of clinical signs was observed. Multiple impression smears of the lesions and a bacterial culture were negative by day 21. The patient achieved complete remission within 4 months of treatment and maintained remission for the 2-year observation period with continued use of the medication. Topically administered therapeutics containing essential fatty acids and plant extracts may offer a viable treatment option for recurrent cases of bacterial infectious skin lesions in Indian rhinocerotidae.
... Its safeguarding actions on gastrointestinal, cardiovascular, respiratory, and nervous systems has also been evident. 7,8 Multiple mechanisms can accomplish the amelioration of CVD, for example, improving coronary vasodilatation, improving endothelial function, inhibiting platelet aggregation, reducing lipoprotein (LDL) oxidation, reducing inflammatory response, decreasing oxidative stress, and providing antioxidant protection. [9][10][11][12][13][14][15] Evidence from observational and interventional studies is inconclusive regarding the effect of honey consumption on clinical cardiovascular risk factors such as lipid profile. ...
... Manuka honey is known to promote wound healing and to have effects on living cells (some original refs). Recent evidence supports the healing effect of manuka honey on wounds, as it has the ability to improve the response to oxidative damage and the stimulation of cell proliferation (Alvarez-Suarez et al., 2016). Manuka honey can reduce LPS-induced inflammation of mouse RAW 246.7 macrophages . ...
Honey is a natural product with a sweet flavor. Honey is made by the honeybee (Apis mellifera L.) from the nectar of flowers or other plant secretions that are collected near the hive. These products are mixed with bee saliva and stored. Several studies have demonstrated that honey exhibits antioxidant, antimicrobial, nematicidal, antifungal, anticancer, and anti‐inflammatory activities. These properties are influenced by the plants from which the secretions are harvested, from the naturally occurring compounds present in the nectar. Studies of the properties and applications of honey have distinguished honey from other natural products due to the presence of certain compounds and due its bioactive properties. The focus of this review is to discuss the identified and isolated compounds from monofloral honey produced by A. mellifera, with specific emphasis on antioxidant and antimicrobial properties of honey and its therapeutic health benefits.
... Both extracts were rich in polyphenols which are compounds that exert some of their antioxidant effects by promoting the secretion of antioxidant enzymes (e.g., SOD and CAT) and by inducing HO-1-related detoxification enzymes. Glutathione is involved in the detoxification of xenobiotics [80]. In addition, aqueous and methanol extracts contain flavonoids and saponins that exert their antioxidant power by free radical scavenging [81,82]. ...
Among the most exploited species in Cameroon, Alstonia boonei is widely used in African medicine for the relief of several pathologies including gastrointestinal disorders. This study was conducted in order to assess the effects of aqueous and methanol stem-bark extracts of Alstonia boonei on DSS- (dextran sodium sulfate-) induced intestinal colitis and to determine its antioxidant potential. The classes of secondary metabolites present in these extracts were determined by chemical screening. The production of TNF-α, IL-6, IL-1β, and PGE2 was performed by in vitro ELISA analysis. Anticolitis effects were determined using an in vivo model of ulcerative colitis induced by DSS. The colitis was induced with a double dose of DSS (3% and 1%), and the aqueous and methanol extracts were administered orally from the 6th day after commencement of induction. The phytochemical screening revealed the presence of six classes of secondary metabolites in these crude extracts: tannins, saponins, alkaloids, steroids, flavonoids, and phenols. Methanol and aqueous extracts of Alstonia boonei significantly (P < 0.001) inhibited TNF-α, IL-6, IL-1β, and PGE2 production stimulated by LPS. Both extracts at all doses significantly reduced (P < 0.01, P < 0.001) the signs of DSS-induced colitis in the Wistar rats by decreasing inflammation and chronic colon damage. In addition, the extracts significantly (P < 0.001) reduced malondialdehyde and nitric oxide levels in the colon and significantly (P < 0.01) increased superoxide dismutase and catalase and reduced glutathione (P < 0.05). Both extracts showed greater activity than the reference substance (prednisolone 4 mg/kg) used in this study. This study has demonstrated that aqueous and methanol extracts of Alstonia boonei stem bark have healing properties against colitis experimentally induced by DSS in rats.
... Nrf2 signaling plays an irreplaceable factor in oxidative stress-induced tissue injures and activation of Nrf2 pathway protected cells from oxidative insults [11,25]. Upon the activation of oxidative insults, Nrf2 translocates from cytoplasm to nucleus and subsequently activates downstream antioxidant genes [26]. ...
Background:
Gut barrier dysfunction with alterant mucosal permeability during sepsis is a challenge problem in clinical practice. Intestinal epithelial cells (IECs) are strongly involved in mucosal oxidative stress and inflammatory response. The current study aimed at investigating the effect of MitoQ, a mitochondrial targeted antioxidant, in the treatment of intestinal injury and its potential mechanism during sepsis.
Methods:
30 minutes before sepsis induction by lipopolysaccharide (LPS) treatment, mice were treated with MitoQ. Intestinal histopathology, mucosal permeability, inflammatory cytokines, and mucosal barrier proteins were evaluated in the present study.
Results:
MitoQ pretreatment significantly decreased the levels of plasma diamine oxidase, D-lactate, and intestinal histological damage and markedly restored the levels of tight junction proteins (ZO-1 and occludin) following LPS challenge. Furthermore, MitoQ inhibited the LPS-induced intestinal oxidative stress and inflammatory response, evidenced by increased levels of intestinal superoxide dismutase and glutathione, and decreased levels of intestinal IL-1, IL-6, TNF-α, and nitric oxide levels. Mechanically, we found that MitoQ inhibited the oxidative stress via activating nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream antioxidant genes, including HO-1, NQO-1, and GCLM.
Conclusions:
MitoQ exerts antioxidative and anti-inflammatory effects against sepsis-associated gut barrier injury by promoting Nrf2 signaling pathway.
... Several studies have reported a strong correlation between the total polyphenol and flavonoid contents and the antioxidant capacity of honey (4,88) . The antioxidant activity of honey is accredited to the ability of its bioactive compounds to scavenge or reduce the formation of free radicals, along with the improvement of mitochondrial functionality and the inhibition of DNA damage and lipid peroxidation (31) . ...
Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.
... Regarding the antibacterial activity honey is effective against both Grampositive and Gram-negative bacteria [120]. It sterilizes the wounds, stimulate tissue re-growth, reduces edema and scar formation, affects simple wounds, burns, diabetic foot ulcers, and pressure ulcers [121][122][123]. An enzyme glucose oxidase present in honey is also responsible for antimicrobial activity by converting glucose into δ-gluconolactone, which is further hydrolyzed to gluconic acid and hydrogen peroxide (H 2 O 2 ). ...
Bioactive compounds are important constituents of the food that provide health benefits beyond basic nutrition. The animal products contain health promoting substances possessing antioxidant, antithrombotic, anti- inflammatory and anti-carcinogenic properties. In the last two decades, there is enormous increase in the production and consumption of bioactive foods. Food items from animal source include milk, meat, egg and honey. Milk furnishes a wide range of bioactivities that protect infants and adults against illness. The milk bioactive components comprise of specific proteins, antibacterial peptides, lipids and oligosaccharides that are effective in gastrointestinal and immunological development and also improve the probiotic action. On the other hand, meat is a source of endogenous antioxidants such as coenzyme Q10, glutathione, lipoic acid etc and other bioactive substances like carnitine, carnosine, conjugated linoleic acid and essential omega-3 polyunsaturated fats. Some of these ingredients are essential to cellular energy production and to improve the physiological functions of the human body. Eggs are associated with bioactive constituents containing choline, phospholipids, carotenoids e.g. lutein and zeaxanthin and proteins. In addition, antioxidants present in egg yolk prevent age-related macular degeneration. Honey act as a natural therapeutic agent consists of phenolic compounds such as flavonoids and phenolic acids have shown the antimicrobial, antiviral, antifungal, anticancer and anti-diabetic activity. The food technologists have adopted different strategies to modify the concentration of healthy compounds in animal based products to produce safe and healthier functional food products. Hence, animal based bioactives are potentially involved as protective compounds for a number of chronic diseases and can be used as good health food.
... Furthermore, carob honey might enhance Nrf2 pathway and potentiate the antioxidant system similar to other honeys. It was found that Manuka honey can activate the AMPK/Nrf2/ARE signalling pathway (54). Another study showed that honey moderately upregulated the Nrf2 mRNA expression level in the kidney (47). ...
Background/Aim. Various honey samples exhibited protective effect against drug and chemical induced toxicity. The study was designed to determine the antioxidant content and activity of carob honey and to investigate its hepato-renal protective effect in carbon tetrachloride (CCl4) induced kidney and liver injury in rats.
Material and Methods. Phenolic, flavone and flavonol in carob honey were quantified. DPPH, ABTS�þ, ferric reducting antioxidant power, and total antioxidant activity were used to evaluate the antioxidant activity. Rats were used for the experiment, and received either intraperitoneal injection of CCl4 (1 mL/kg.b.wt); honey (orally, 2 g/kg.b.wt) and CCl4; or honey. Liver and kidney function parameters were assessed. Oxidative parameters including lipid peroxidation (MDA), protein carbonyl formation (PCO), advanced protein oxidation products (AOPP), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and ascorbic acid were measured in the kidney and liver tissues.
Results. CCl4 caused a significant elevation of liver enzymes, lactic acid dehydrogenase, blood glucose, uric acid, blood urea and serum creatinine as compared to the control
group. Also, it significantly increased MDA, PCO and AOPP level, and markedly decreased GHS, ascorbic acid, CAT and GPx in the liver and kidney tissues. These changes were significantly ameliorated by carob honey before and after CCl4 administration. Honey alone did not cause significant changes as compared to the control group.
Conclusion. The data showed for the first time that carob honey has high antioxidant content, antioxidant property, and protective effect against CCl4 induced kidney and liver toxicity by maintaining the activity of antioxidant defense system.
Key Words: Carbon tetrachloride, Carob honey, Antioxidant, Oxidative stress, Liver, Kidney
... An activity closely linked to antibacterial capacity is wound healing. The ability of honey to sterilize the wounds, stimulate tissue re-growth, and to reduce edema and scar formation, affects simple wounds, burns, diabetic foot ulcers, and pressure ulcers [6,58,59]. ...
Honey is a natural substance appreciated for its therapeutic abilities since ancient times. Its content in flavonoids and phenolic acids plays a key role on human health, thanks to the high antioxidant and anti-inflammatory properties that they exert. Honey possesses antimicrobial capacity and anticancer activity against different types of tumors, acting on different molecular pathways that are involved on cellular proliferation. In addition, an antidiabetic activity has also been highlighted, with the reduction of glucose, fructosamine, and glycosylated hemoglobin serum concentration. Honey exerts also a protective effect in the cardiovascular system, where it mainly prevents the oxidation of low-density lipoproteins, in the nervous system, in the respiratory system against asthma and bacterial infections, and in the gastrointestinal system. A beneficial effect of honey can also be demonstrated in athletes. The purpose of this review is to summarize and update the current information regarding the role of honey in health and diseases.
... Gallic acid, a phenolic compound in honey, can decline lipid perox- idation by free radical scavenging (36). Previous studies have reported that kaempferol, pinobanksin, and chrysin phenolic components in honey by repression of NF-kB sig- naling decreased the production of MDA and NO (29,30,37). NF-κB induces proinflammatory gene expression un- der oxidative stress and inflammatory conditions and in- creases cytokine production (e.g. ...
Background: Overproduction of reactive oxygen species (ROS) causes increased lipid peroxidation, decreased intestinal epithelial barrier integrity, and ultimately mucosal disruption and ulceration. Several studies have confirmed the antioxidant, anti-inflammatory, and immunomodulatory properties of Spirulina Platensis (SP), edible blue-green algae, in various inflammatory diseases. In addition, natural honey, a source of phenolic and flavonoid compounds, is a powerful antioxidant, which can help prevent chronic oxidative stress and subsequent inflammation. Objectives: In this study, we examined and compared the protective effects of SP and honey on ulcerative colitis induced by acetic acid (AA) in rats. Methods: Forty male rats were allocated into five groups (N = 8) and received pretreatment for 32 consecutive days. The administrations were as follows: group 1 (control) and group 2 (AA-colitis group): normal saline, group 3: 1 ml honey/day, group 4: 1 ml honey/day plus 1 g/kg SP, and group 5: 1 g/kg SP. Colitis was induced on the 30th day in groups 2 to 5. On day 32, the clinical activity was determined and anesthetized animals were sacrificed. Serum interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), superoxide dismutase (SOD), colonic tissues myeloperoxidase (MPO), prostaglandin E2 (PGE2), malondialdehyde (MDA), nitric oxide (NO), and colonic weight/length ratio were determined. In addition, histopathological changes of the colon were observed microscopically. Results: The inflammatory markers (PGE2, MDA, NO, IL-6, IL-1β, MPO, and TNF-α) were significantly lower in the pretreatment groups than in the AA-colitis group (P values < 0.05). PGE2 [median (IQR)] of the honey, SP + honey, and SP groups was [0.76 (0.33)], [0.75 (0.40)], and [0.87 (0.86)], respectively, compared to the AA-colitis group [2.60 (2.23)] (P values < 0.041). MDA values were [6.52 (3.57)], [6.09 (3.59)], and [5.85 (4.92)] vs. [16.60 (12.03)] (P values < 0.046) and IL-1β values were [42.20 (8.2)], [41.76 (18.10)], and [42.93 (14.09)] vs. [79.54 (40.79)] (P values < 0.044). Also, SOD, GSH, GPx, and TAC [median (IQR)] were significantly higher in the pretreatment groups than in the AA-colitis group (P values < 0.05). For example, TAC values of the honey, SP + honey, and SP groups were [0.164 (0.08)], [0.14 (0.05)], and [0.16 (0.10)], respectively, vs. the AA-colitis group [0.08 (0.01)] (P values < 0.028). Conclusions: Honey and SP are favorable foods in preventing oxidative stress and inflammatory diseases such as ulcerative colitis.
... The capacity of several steroidal glycosides from Easter lily (Lilium longiflorum Thunb.) bulbs or Manuka honey to promote dermal fibroblast migration in vitro through the stimulation of nitrite production has been previously reported [49,50]. Therefore, our results could explain, to a certain degree, the possible topical use of both extracts to promote cellular migration and proliferation against tissue oxidative damage to promote skin tissue repair. ...
BACKGROUND: Andean blackberries (Rubus glaucus Benth) and Andean blueberries (Vaccinium floribundum Kunth) are wild berries consumed and commercialised by the indigenous people of the Andean regions of Ecuador. OBJECTIVE: This study aims to determine the chemical composition and the ability of A. blackberries and A. blueberries to protect human dermal fibroblast (HDFa) against cytotoxic oxidative damage. METHODS: Total phenolic, flavonoid, anthocyanins and tannins content were determined spectrophotometrically, while vitamin C and carotenes were determined by HPLC. Total antioxidant capacity was determined by the Ferric Reducing Antioxidant Power (FRAP) assay, the hydrogen peroxide scavenging activity and the DPPH and superoxide radical scavenging capacity. HDFa was pre-treated with A. blackberries or A. blueberries crude extract, subjected to a model of oxidative stress using the stressor 2,2’-azobis(2-amidinopropane) dihydrochloride (AAPH) and the markers of cell cytotoxic damage (intracellular ROS levels, catalase, superoxide dismutase and glutathione activities, lipid peroxidation, protein oxidation and ATP and nitrite levels) were determined. RESULTS: A. blueberries showed significantly high values of total phenolic, flavonoid, anthocyanin, lutein tannin content, whilst A. blackberries showed the highest values of vitamin C and β -carotene. After HDFa was pre-incubated with crude extracts of A. blackberries and A. blueberries, the markers of oxidative damage were significantly improved compared with the stressed cells group. In all cases, crude extract of A. blueberries showed a higher protective effect compared to A. blackberries. CONCLUSION: A. blackberry and A. blueberry attenuated the oxidative damage in HDFa showing that both fruits may represent a relevant source of bioactive compounds with promising benefits for human health.
... These results suggested that the MAPK pathway plays critical roles in Nrf2-signal activation. Whether other pathways in addition to the MAPK pathway, such as those of protein kinase C (PKC), 42 AMP-activated protein kinase (AMPK), 48 and glycogen-synthase kinase-3β (GSK-3β), 49 regulate the activation of Nrf2 signals and thus the induction of cytoprotective enzymes requires further study. ...
The current study evaluates the protection and potential mechanisms of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-Butyl Hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) leakeage and glutathione (GSH) levels. Further mechanistic study showed that tangeretin up-regulated the expression of heme oxygenasae-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1). Morever, tangeretin induced antioxidant responsive element (ARE)-dependent luciferase activation, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and mitogen-activated protein kinases (MAPKs) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly owing to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK/Nrf2/ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
... Cells were centrifuged once to remove the medium and re-suspended again in 100 µL PBS. Finally, samples were analyzed with the Tali® Image-Based Cytometer and the results were expressed as the percentage of cells with increased ROS levels compared with the control (Alvarez-Suarez et al., 2016;Giampieri et al., 2017). ...
The effects of ground pistachio kernel extracts have been evaluated on cellular viability, intracellular reactive oxygen species (ROS) production and cell death in MCF-7 breast cancer cells. Results showed a significant decrease in cell viability in a dose and time dependent manner. 48 h-treatments with different concentrations of the extracts induced intracellular ROS generation and showed that cell death was in an apoptosis-independent manner. It was also found that 48 h-treatments led to a dose dependent reduction in both extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) with respect to untreated cells. Therefore, a considerable alteration of cell bioenergetics would occur as consequence of such treatments. Combination of oxidative stress and bioenergetic alterations could be responsible, at least in part, of the cell death observed in the present model. In conclusion, pistachio kernel extract showed promising beneficial effects that could be exploited as a “natural adjuvant” in combination with chemotherapy treatment.
... A recent study [106] brings new evidence in demonstrating the effects of Manuka honey in wound healing. The Honey, compared to sucrose, had lower GI and PII in both patients and control groups. ...
Diabetes is a metabolic disorder with multifactorial and heterogeneous etiologies. Two types of diabetes are common among humans: type 1 diabetes that occurs when the immune system attacks and destroys insulin and type 2 diabetes, the most common form, that may be caused by several factors, the most important being lifestyle, but also may be determined by different genes. Honey was used in folk medicine for a long time, but the health benefits were explained in the last decades, when the scientific world was concerned in testing and thus explaining the benefits of honey. Different studies demonstrate the hypoglycemic effect of honey, but the mechanism of this effect remains unclear. This review presents the experimental studies completed in the recent years, which support honey as a novel antidiabetic agent that might be of potential significance for the management of diabetes and its complications and also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent.
... The nonenzymatic antioxidants comprise vitamins E and C, glutathione (GSH), and some small molecules, while exogenous antioxidants include some micronutrients [24,80]. These antioxidants also support proliferation and migration of human dermal fibroblasts and mitochondrial function to assist healing [81]. ...
Honey clasps several medicinal and health effects as a natural food supplement. It has been established as a potential therapeutic antioxidant agent for various biodiverse ailments. Data report that it exhibits strong wound healing, antibacterial, anti-inflammatory, antifungal, antiviral, and antidiabetic effects. It also retains immunomodulatory, estrogenic regulatory, antimutagenic, anticancer, and numerous other vigor effects. Data also show that honey, as a conventional therapy, might be a novel antioxidant to abate many of the diseases directly or indirectly associated with oxidative stress. In this review, these wholesome effects have been thoroughly reviewed to underscore the mode of action of honey exploring various possible mechanisms. Evidence-based research intends that honey acts through a modulatory road of multiple signaling pathways and molecular targets. This road contemplates through various pathways such as induction of caspases in apoptosis; stimulation of TNF- α , IL-1 β , IFN- γ , IFNGR1, and p53; inhibition of cell proliferation and cell cycle arrest; inhibition of lipoprotein oxidation, IL-1, IL-10, COX-2, and LOXs; and modulation of other diverse targets. The review highlights the research done as well as the apertures to be investigated. The literature suggests that honey administered alone or as adjuvant therapy might be a potential natural antioxidant medicinal agent warranting further experimental and clinical research.
... Furthermore, carob honey might enhance Nrf2 pathway and potentiate the antioxidant system similar to other honeys. It was found that Manuka honey can activate the AMPK/Nrf2/ARE signalling pathway (54). Another study showed that honey moderately upregulated the Nrf2 mRNA expression level in the kidney (47). ...
Honey contains various biological active substances including proteins, free amino acids, enzymes, vitamins, organic acids, flavonoids, phenolic acids and other phytochemicals. Honey has antioxidant, antiviral, antimicrobial, antiparasitic, and antimutagenic properties. This might explain its wide range of the therapeutic and biological activities. The present study was aimed to investigate the hepatoprotective effect of carob honey on carbon tetrachloride (CCl4) induced liver injury. The Wistar rats were used for the study and the hepatotoxicity was induced by intraperitoneal injection of CCl4 (1ml/kh b.w.) after four days of pretreatment with carob honey (2g/kg b.w. : orally). The hepatoprotective effect of carob honey was determined by assessing the biochemical parameters in serum and the markers of oxidative stress in liver. Pretreatment with honey prior the administration of CCl4 significantly prevented the release of transaminases, alkaline phosphatase, lactate dehydrogenase, significantly inhibited lipid peroxidation (MDA) , protein carbonyl (PCO) formation and Advanced protein oxidation products (AOPP) in liver and markedly enhanced catalase , glutathione peroxidase and ascorbic acid in liver. This findings confirmed the hepatoprotective effect of carob honey against CCl4 toxicity.
... The authors found a therapeutic potential of that honey against KA-induced oxidative stress and neurodegeneration through an antioxidant effect. In another study, AlvarezSuarez et al.[47]reported that the Manuka honey protected against apoptosis, intracellular reactive oxygen species production, and lipid and protein oxidative damage. Moreover, they also found that the honey protected mitochondrial functionality, promoted cell proliferation and activated the AMPK/Nrf2/ARE (Kelch ECH associating protein 1/NF-E2-related factor 2/antioxidant responsive elements) signalling pathway, as well as the expression of the antioxidant enzymes such as superoxide dismutase and catalase. ...
Portuguese honeys (n = 15) from different botanical and geographical origins were analysed regarding their quality parameters (diastase activity, hydroxymethylfurfural content, moisture and pH), colour (L∗ a∗ b∗) and antioxidant profile (total phenolics content, total flavonoids content, DPPH∗ scavenging activity, and ferric reducing power). The samples were analysed fresh and after 4-years of storage (at 25°C and protected from light). The hydroxymethylfurfural content and diastase activity of the fresh samples were in accordance with the recommended values described in the legislation. In general, the antioxidant activity of the samples correlated more with the bioactive compounds content than with colour. The storage affected differently each individual sample, especially regarding the antioxidant profile. Nevertheless, although in general the lightness of the samples decreased (and the redness increased), after 4 years, 11 samples still presented acceptable diastase activity and hydroxymethylfurfural values.
Honey has been used by a wide variety of cultures across the world and for thousands of years to prevent infection and improve wound healing. Recently, Manuka honey has been demonstrated to be a potent antibacterial and anti‐inflammatory therapeutic and has been incorporated into an array of wound dressings, as well as being ingested for its anti‐inflammatory and antioxidant effects. Burgeoning investigation into Manuka honey's potential as a biomaterial additive has shown promising results in reducing acute inflammatory behavior from neutrophils, the most abundant leukocyte in the body, and the potent drivers of the initial immune response to implanted biomaterials. This paper discusses the most abundant antioxidant chemicals found in Manuka honey and explains their contribution to the anti‐inflammatory and prowound resolution effects seen by Manuka honey therapeutics. This paper also examines the benefits and drawbacks to current Manuka honey therapies and provides future potential uses for Manuka honey‐inspired therapeutics that could greatly benefit host–biomaterial integration, reduce scar tissue development at the site of implantation, and lower discomfort to the patient caused by biomaterial implantation. Burgeoning investigation into Manuka honey's potential as a biomaterial additive has shown promising results in reducing acute inflammatory behavior from neutrophils, the most abundant leukocyte in the body, and the potent drivers of the initial immune response to implanted biomaterials. This paper discusses the most abundant antioxidant chemicals found in Manuka honey and explains their contribution to the anti‐inflammatory and prowound resolution effects seen by Manuka honey therapeutics.
Purpose A date and honey mixture is used in Indonesia to promote wound healing. However, no studies have evaluated its effects. Thus, this study evaluated the effectiveness of the date and honey mixture in promoting diabetic foot ulcer(DFU)healing, and its effects on biofilm intensity and biomarker levels. Methods This observational study enrolled 30 patients with recurrent DFU treated using the date and honey mixture and 30 patients with recurrent DFU treated only using honey. Both groups were observed every 2 weeks for up to 8 weeks. The Kaplan-Meier method and log-rank test were used to compare the DFU healing proportion. Moreover, the Cox proportional-hazards model was used to assess the effects of the date and honey mixture on wound healing. Superoxide dismutase 3(SOD3)and interleukin(IL)-6 were evaluated as oxidative stress and inflammatory status markers, respectively. These biomarkers and biofilms were collected using wound blotting every 2 weeks. The linear mixed-effect model was performed for biomarkers.
Background
Recently, there is increasing awareness focused on the identification of naturally occurring anticancer agents derived from natural products. Manuka honey (MH) has been recognized for its biological properties as antimicrobial, antioxidant, and anticancer properties. However, its antiproliferative mechanism in hepatocellular carcinoma is not investigated. The current study focused mainly on investigating the molecular mechanism and synergistic effect of anticancer properties of MH on Doxorubicin (DOX)-mediated apoptotic cell death, using two different p53 statuses (HepG2 and Hep3B) and one non-tumorigenic immortalized liver cell line.
Results
MH treatment showed a proliferative inhibitory effect on tested cells in a dose-dependent manner with IC 50 concentration of (6.92 ± 0.005%) and (18.62 ± 0.07%) for HepG2 and Hep3B cells, respectively, and induced dramatic morphological changes of Hep-G2 cells, which considered as characteristics feature of apoptosis induction after 48 h of treatment. Our results showed that MH or combined treatments induced higher cytotoxicity in p53-wild type, HepG2, than in p53-null, Hep3B, cells. Cytotoxicity was not observed in normal liver cells. Furthermore, the synergistic effect of MH and Dox on apoptosis was evidenced by increased annexin-V-positive cells and Sub-G1 cells in both tested cell lines with a significant increase in the percentage of Hep-G2 cells at late apoptosis as confirmed by the flow cytometric analysis. Consistently, the proteolytic activities of caspase-3 and the degradation of poly (ADP-ribose) polymerase were also higher in the combined treatment which in turn accompanied by significant inhibitory effects of pERK1/2, mTOR, S6K, oncogenic β-catenin, and cyclin D1 after 48 h. In contrast, the MH or combined treatment-induced apoptosis was accompanied by significantly upregulated expression of proapoptotic Bax protein and downregulated expression of anti-apoptotic Bcl-2 protein after 48 h.
Conclusions
Our data showed a synergistic inhibitory effect of MH on DOX-mediated apoptotic cell death in HCC cells. To our knowledge, the present study provides the first report on the anticancer activity of MH and its combined treatment with DOX on HCC cell lines, introducing MH as a promising natural and nontoxic anticancer compound.
Manuka honey (MH) is a mono-floral honey obtained from the Manuka tree (Leptospermum scoparium) belonging to the Myrtaceae family and grows as a shrub or a small tree mostly throughout New Zealand and Eastern Australia. MH is highly valued for its non-peroxide antibacterial properties mainly attributed to its exclusive content of methylglyoxal (MGO). Additionally, MH is rich in macro-and micro-nutrients including, sugars, free amino acids, proteins, enzymes, essential minerals, vitamins, and various secondary metabolites (flavonoids, phenolic acids, and 1, 2-dicarbonyl compounds). The presence of these beneficial phytochemicals is directly linked to its favored health benefits viz., wound healing, anticancer, antioxidant, and anti-inflammatory effects. Significant modern pharmacological and clinical evidence have highlighted the wide medicinal applications of MH as a unique mono-floral honey. This comprehensive review capitalizes on MH with emphasis on the interrelationship between its holistic chemical composition, metabolism, action mechanisms, and health effects. Moreover, the review recapitulates the diverse health benefits of MH and related patents in food and functional food applications.
MH health benefits are credited to its unique chemical composition. It represents an alternative remedy for different ailments to include bacterial, fungal, parasitic, and viral infections, and is currently exploited in a massive number of patents. Nevertheless, further studies are needed to uncover its action mechanism in wound healing, how to improve its pharmacokinetics, and to identify its bio-transformed metabolites inside the body.
Background and objectives
A healthy oral environment features a rapid turnover rate of epithelium cells capable of regeneration and repair, with the oral epithelium contributing as a physical barrier and immune defense. However, the oral cavity can be subjected to unique damage, such as ulcerations. Honey is reported as a therapeutic agent for wound healing, due to its antioxidant, antibacterial and anti-inflammatory properties.
Methods
A systematic review was performed following the PRISMA 2015 Guidelines, to assess the efficacy and safety of the therapeutic use of honey in the oral cavity. Four electronic databases were searched (PubMed, Cochrane Library, Scopus, and Web of Science) for randomized controlled trials examining the effect of honey on oral cavity conditions.
Results
In total, 2,832 records were identified, and after applying exclusion criteria, 13 studies were included. Honey was applied topically throughout, for chemotherapy or radiotherapy-induced oral mucositis (n = 11), dental wounds (n = 1), and recurrent aphthous stomatitis (n = 1), all of which are ulcerations with different pathologies. In the majority of studies (12/13), honey reduced the severity and/or duration of the condition compared with control groups (all p<0.05). However, a group treated with Manuka honey (n = 1) experienced adverse effects and considerable participant attrition.
Conclusions
Honey is an effective treatment for a range of oral ulcerative conditions. Future research should focus on compositional analysis of honeys to determine those with optimal beneficial properties, and whether Manuka honey is safe to use in the oral cavity.
The aim of this study was to investigate and compare the change in the total content of phenolic compounds, flavonoids, and the antioxidant capacity in Manuka Honey (MH) after gastrointestinal digestion and different purification methods. MH was subjected to an in vitro gastrointestinal simulation process, and various spectrophotometric analyses [total phenolic content, total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl, ferric ion reducing antioxidant power, and Trolox equivalent antioxidant capacity] were carried out on raw MH and on bioaccessible and eliminated fractions. Our results demonstrated that there was a significant decrease in the quantity of phenolic compounds (between 3.59% and 1.52% of the total amount of phenolic compounds found in undigested honey) and flavonoids in the bioaccessible fraction (between 15% and 19% of the TFC found in undigested honey) after gastrointestinal digestion and that the decrease was lower also for the antioxidant activity of the samples (ranging between 12.39% and 13.67% of the activity of raw honey), suggesting that the phenolic compounds are not only responsible for this activity. Additionally, we demonstrated that the purification method can affect the amount of phenolic compounds and the antioxidant capacity, showing that centrifugation is the most efficient method of purification.
In the present investigation scratch wound assay was used to study the ability of several combinations of each flavonoid (chrysin, naringenin or resveratrol) with β-sitosterol to heal wounds in vitro. MTT test was performed to determine if the combination of flavonoid with β-sitosterol was toxic to fibroblasts or not. Also, superoxide dismutase (SOD) activity and interleukin-1β (IL-1β) concentrations were measured. The best closure rates were obtained with β-sitosterol combined with naringenin and β-sitosterol combined with resveratrol. The combination that produced the best closure rate namely β-sitosterol with naringenin increased SOD activity significantly. However, this combination was not better than naringenin or β-sitosterol alone in reducing IL-β concentration. The results of MTT test indicated that the combination as well as β-sitosterol alone or naringenin alone has no toxic effect on fibroblasts. In conclusion, the combination of β-sitosterol and naringenin exerted a synergistic effect on wound closure without decreasing the viability of fibroblasts, increased antioxidant defense mechanism and decreased IL-β.
Isoflavones are one group of the major flavonoids and possess multiple biological activities due to their antioxidant properties. However, a clear antioxidant mechanism of dietary isoflavones is still remained to be answered. In this study, the effects of isoflavones on the nuclear factor E2‐related factor 2 (Nrf2)–antioxidant response element (ARE) signaling pathway and the underlying molecular mechanisms were investigated. Results showed that isoflavones are potential Nrf2–ARE activators while their activities were structure dependent. Biochanin A (BCA), an O‐methylated isoflavone with low direct antioxidant activity, can effectively protect HepG2 cells against tert‐butyl hydroperoxide (t‐BHP)‐induced oxidative damage via activation of the Nrf2 signaling, and thereby the induction of downstream cytoprotective enzymes including NAD(P)H quinone oxidoreductase‐1, heme oxygenasae‐1, and glutamate‐cysteine ligase catalytic subunit. A molecular docking study revealed that BCA could directly bind into the pocket of Kelch‐like erythroid cell‐derived protein with CNC homology (ECH)‐associated protein 1 (Keap1), a cytoplasmic suppressor of Nrf2, to facilitate Nrf2 activation. The upstream mitogen‐activated protein kinase (MAPK) pathways were also involved in the activation of Nrf2 signaling. These findings indicate that the protective actions of dietary isoflavones against oxidative damage may be at least partly due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2−ARE signaling pathway.
Background: Manuka honey has attracted the attention of the scientific community for its antimicrobial and antioxidant properties. The active compounds of manuka honey to which its myeloperoxidase activity inhibition is owed are methyl syringate (MSYR) and leptosin (a novel glycoside of MSYR). The non-peroxide antibacterial activity is attributed to glyoxal, 3-deoxyglucosulose, and methylglyoxal. These properties make it an inexpensive and effective topical treatment in wound management. This study has focused on the evaluation of the effect of manuka honey and acacia honey on wound healing in nondiabetic and streptozotocin-induced diabetic rats. Materials and Methods: This study was conducted on a total of 42 rats (six rats in each group) and respective drug/substance was topically applied once daily on the excision wound for 21 days.
Induction of diabetes was carried out in rats in groups IV, V, VI, and VII only. Measurement of wound contraction was carried out on days 3, 6, 9, 12, 15, 18, and 21 after operation. Time taken for the complete epithelization was recorded along with a histopathological examination of the healed wound bed. Results: Topical application of manuka honey achieved ≥80% wound contraction on day 9 after operation in both the nondiabetic and diabetic group. Complete epithelization was achieved 2 days earlier than the normal epithelization time in the manuka group. Histopathological examination showed well formed keratinized squamous epithelium with normal collagen tissue surrounding hair
follicles. Conclusion: This study provides good outcome with respect to wound healing (especially in diabetic condition) when manuka honey was compared to acacia honey and standard treatment.
Manuka honey (MH) is a monofloral honey from Australia and New Zealand, well-known for its healthy properties, such as antioxidant, antimicrobial and wound healing capacities. The aim of this work was to assess the phenolic composition and the total antioxidant capacity (TAC) of MH, as well as its effects on cellular viability, proliferation, apoptosis and metabolism in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, highlighting the molecular mechanisms involved. Up to 18 compounds were identified in MH, with gallic acid and quercetin as the major ones; MH showed also remarkable TAC. In addition, MH was able to enhance cellular viability, decrease apoptosis, promote wound healing and attenuate inflammation in a dose-dependent manner, by reducing the expression of caspase 3, p-p38 and p-Erk1/2 proteins, in macrophages stressed with LPS. In addition, it improved mitochondrial respiration and glycolytic activities, stimulating the expression of p-AMPK, SIRT1 and PGC1α, counteracting in this way the deleterious effects of LPS treatment. In conclusion, one of the possible mechanisms by which MH exerts its beneficial effects could be to its capacity to improve cellular viability, promote proliferation and enhance energetic metabolism, by modulating the expression of several proteins involved in apoptosis, inflammation, metabolism and mitochondrial biogenesis.
Skin and chronic wound infections are an increasing and urgent health problem worldwide. Their management is difficult and the development of antibiotic resistance by both planktonic and biofilm-associated bacteria necessitates the use of alternative treatments. The purpose of this study was to compare the antimicrobial activity of four honeys from different floral and geographical origins: Melipona beecheii honey (Cuba) and three Apis mellifera honeys [Manuka honey (New Zealand), A. mellifera honey (Cuba), and African honey (Kenya)]. The physicochemical parameters were within the ranges reported for these honeys and M. beecheii honey stood out due to its acidic character. An agar incorporation technique was used to determine the minimum active dilution of each honey against 52 clinical isolates (34 Gram-positive, 17 Gram-negative, and 1 Candida albicans). The antibiofilm activity of honeys was tested by assessing their ability to inhibit biofilm formation and to disrupt preformed biofilms. Overall, M. beecheii honey had the highest antimicrobial and antibiofilm activity, although a marked disruption in preformed biofilms was shared by all tested honeys. Structural changes induced by M. beecheii honey on Staphylococcus aureus and Pseudomonas aeruginosa cells were observed by transmission electron microscopy suggesting that this honey has a potent antimicrobial action and may be an excellent candidate for the development of topical preparations for the treatment of infected wounds.
The objective of this study was to determine the phytochemical profiles and antioxidant activities of three highland barley varieties. The free, bound, and total phenolic content of highland barley, respectively ranged from 44.52 to 178.37 mg gallic acid equivalents (GAE)/100 g dry weight (D. W.), 121.69–302.55 mg GAE/100 g D. W., and 166.21–480.92 mg GAE/100 g D. W. Besides, the free, bound, and total flavonoid content, respectively, ranged from 15.71 to 35.18 mg rutin equivalents (RE)/100 g D. W., 39.37–86.93 mg RE/100 g D. W., and 59.13–102.64 mg RE/100 g D. W. The 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging abilities, oxygen radical absorbance capacities, ferric reducing antioxidant power values, and cellular antioxidant activities of the bound extractions of highland barley were higher than those of the free extractions. However, the free polyphenol extracts had stronger inhibitory effects on HepG2 cell proliferation than the bound extracts.
Practical applications
Highland barley is a principal food crop that is widely cultivated in the west and southwest regions of China. Highland barley is usually rich in phenolic compounds, however, the phenolic compounds content and antioxidant activities of highland barley were underestimated because the bound phytochemical fraction was not included in the analysis. In this study, three highland barleys from different region of China were used to analysis the free and bound total phenolics and total flavonoids, as well as the antioxidant activities.
Honey is one of the most popular natural sweet substances. From a chemical point of view, it could be defined as a natural food mainly composed of sugars and water together with minor constituent such as minerals, vitamins, amino acids, organic acids, flavonoids and other phenolic compounds and aromatic substances. Its composition is particularly variable, depending on its botanical and geographical origins. The aim of this chapter is to describe the principal families of compounds present in honey and the analytical methods employed for their analysis, as well as to review the utility of those chemical components to discriminate honeys according to their origin.
Aging is a progressive loss of physiological properties that drive to a decrease of functions and survival. Indeed, aging is the main risk factor for cancer, diabetes, cardiovascular disorders and neurodegenerative diseases. The discovery that the rate of aging is controlled by conserved genetic and biochemical pathways has provoked an unprecedented advance in aging research. The AMPK protein is a metabolic sensor that controls energy homeostasis, resistance to stress, and acts as a qualified cellular housekeeping. The correct regulation of these factors increases health and survival. In this manuscript we will review the molecular pathways regulated by AMPK in the aging process, paying special attention to mitochondrial dysfunction, metabolic deregulation, cell senescence and autophagy.
Honey has been used as a wound dressing for thousands of years, but only in more recent times has a scientific explanation become available for its effectiveness. It is now realized that honey is a biologic wound dressing with multiple bioactivities that work in concert to expedite the healing process. The physical properties of honey also expedite the healing process: its acidity increases the release of oxygen from hemoglobin thereby making the wound environment less favorable for the activity of destructive proteases, and the high osmolarity of honey draws fluid out of the wound bed to create an outflow of lymph as occurs with negative pressure wound therapy. Honey has a broad-spectrum antibacterial activity, but there is much variation in potency between different honeys. There are 2 types of antibacterial activity. In most honeys the activity is due to hydrogen peroxide, but much of this is inactivated by the enzyme catalase that is present in blood, serum, and wound tissues. In manuka honey, the activity is due to methylglyoxal which is not inactivated. The manuka honey used in wound-care products can withstand dilution with substantial amounts of wound exudate and still maintain enough activity to inhibit the growth of bacteria. There is good evidence for honey also having bioactivities that stimulate the immune response (thus promoting the growth of tissues for wound repair), suppress inflammation, and bring about rapid autolytic debridement. There is clinical evidence for these actions, and research is providing scientific explanations for them.
The thermoreceptive transient receptor potential ankyrin 1 (TRPA1) is important in the transmission of itch, and its agonist trans-cinnamaldehyde has occasionally been reported to be a pruritogen in humans. However, no studies have accurately quantified the capabilities of trans-cinnamaldehyde to induce itch and related dysesthetic sensations. The present study examined alterations in somatosensory and vasomotor parameters in response to topical trans-cinnamaldehyde 5% and vehicle (ethanol) in 24 healthy subjects. During the study the following parameters were recorded: itch area and intensity, hyperknesis, alloknesis, neurogenic flare, skin blood flow and temperature. Trans-cinnamaldehyde evoked moderate itch sensation, flare, hyperknesis and alloknesis (p < 0.001). Blood flow and skin temperature were elevated in the area of trans-cinnamaldehyde application (p < 0.001). Significant positive correlations were found between blood flow and skin temperature, itch area and blood flow, and itch area and skin temperature. Topical trans-cinnamaldehyde proved feasible as a human itch model with applicability in studying itch mechanisms or anti-pruritic drug profiling.
Background
Acacia honey (AH) has been proven to improve skin wound healing, but its therapeutic effects on corneal epithelium has not been elucidated to date. This study aimed to investigate the effects of AH on cultured corneal epithelial cells (CEC) on in vitro corneal abrasion wound healing model. Six New Zealand white rabbits’ CEC were isolated and cultured until passage 1. Circular wound area was created onto a confluent monolayer CEC using a corneal trephine which mimicked corneal abrasion and treated with 0.025% AH supplemented in basal medium (BM) and complete cornea medium (CCM). Wound healing was measured as the percentage of wound closure by the migration of CEC on day 0, day 3 and day 6, post wound creation. The morphological changes of CEC were assessed via phase contrast microscopy. Gene and protein expressions of cytokeratin (CK3), fibronectin and cluster of differentiation 44 (CD44) in AH treated groups and control groups were determined by real-time PCR and immunocytochemistry, respectively.
Results
Cultured CEC exhibited similar morphology of polygonal shaped cells in all culture media. CEC cultured in AH-supplemented media showed higher percentage of wound closure compared to the controls. Gene expression of CK3 increased in AH-supplemented groups throughout the study. Fibronectin expression was increased at the initial stage while CD44 expression was increased at day 3, post wound creation. The protein expression of CEC cultured in all media was in accordance to their respective gene expressions.
Conclusion
Supplementation of AH in BM and CCM media accelerates CEC wound closure of the in vitro corneal abrasion model by increasing the expression of genes and proteins associated with CEC wound healing.
AMPK is a serine/threonine protein kinase that has the function of maintaining the balance between ATP production and consumption in most eukaryotic cells. It plays a relevant role in regulating cellular metabolism, preserving cellular energy homeostasis, and is involved in many other cellular processes as well as metabolic ones, including cell cycle regulation and endothelial and vascular relaxation. Recently, the effects of naturally occurring compounds able to prevent and treat diseases through AMPK activation have attracted the attention of many researchers. Among such compounds, flavonoids found in natural sources, like quercetin, genistein, epigallocatechins, resveratrol, have been proposed as AMPK activators. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds, from plant foods, affect the AMPK pathway in healthy and pathological in vitro and in vivo models, paying particular attention to molecular mechanisms involved in diabetes, obesity, metabolic syndrome, cardiovascular disease and cancer
Transient receptor potential ankyrin 1 (TRPA1) is a polymodal excitatory ion channel found in sensory neurons of different organisms, ranging from worms to humans. Since its discovery as an uncharacterized transmembrane protein in human fibroblasts, TRPA1 has become one of the most intensively studied ion channels. Its function has been linked to regulation of heat and cold perception, mechanosensitivity, hearing, inflammation, pain, circadian rhythms, chemoreception, and other processes. Some of these proposed functions remain controversial, while others have gathered considerable experimental support. A truly polymodal ion channel, TRPA1 is activated by various stimuli, including electrophilic chemicals, oxygen, temperature, and mechanical force, yet the molecular mechanism of TRPA1 gating remains obscure. In this review, we discuss recent advances in the understanding of TRPA1 physiology, pharmacology, and molecular function.
Honey has been used as a food and medical product since the earliest times. It has been used in many cultures for its medicinal properties, as a remedy for burns, cataracts, ulcers and wound healing, because it exerts a soothing effect when initially applied to open wounds. Depending on its origin, honey can be classified in different categories among which, monofloral honey seems to be the most promising and interesting as a natural remedy. Manuka honey, a monofloral honey derived from the manuka tree (Leptospermum scoparium), has greatly attracted the attention of researchers for its biological properties, especially its antimicrobial and antioxidant capacities. Our manuscript reviews the chemical composition and the variety of beneficial nutritional and health effects of manuka honey. Firstly, the chemical composition of manuka honey is described, with special attention given to its polyphenolic composition and other bioactive compounds, such as glyoxal and methylglyoxal. Then, the effect of manuka honey in wound treatment is described, as well as its antioxidant activity and other important biological effects.
Aim. The purpose of this study was to determine the in vitro response of cells critical to the wound healing process in culture media supplemented with a lyophilized preparation rich in growth factors (PRGF) and Manuka honey. Materials and Methods. This study utilized cell culture media supplemented with PRGF, as well as whole Manuka honey and the medical-grade Medihoney (MH), a Manuka honey product. The response of human fibroblasts (hDF), macrophages, and endothelial cells (hPMEC) was evaluated, with respect to cell proliferation, chemotaxis, collagen matrix production, and angiogenic potential, when subjected to culture with media containing PRGF, MH, Manuka honey, and a combination of PRGF and MH. Results. All three cell types demonstrated increases in cellular activity in the presence of PRGF, with further increases in activity seen in the presence of PRGF+MH. hDFs proved to be the most positively responsive cells, as they experienced enhanced proliferation, collagen matrix production, and migration into an in vitro wound healing model with the PRGF+MH-supplemented media. Conclusion. This preliminary in vitro study is the first to evaluate the combination of PRGF and Manuka honey, two products with the potential to increase regeneration individually, as a combined product to enhance dermal regeneration.
Transient receptor potential channel ankryn 1 (TRPA1) and transient receptor potential channel vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and are often coexpressed in sensory neurons. Extracts of the first leaves of Kalopanax pictus Nakai (Araliaceae) have been shown to activate hTRPA1 and hTRPV1. Therefore, the effects of six commercially available chemicals (methyl syringate, coniferyl alcohol, protocatechuic acid, hederacoside C, α-hederin, and eleutheroside B) found in K. pictus were investigated on cultured cells expressing hTRPA1 and hTRPV1. Of the six compounds, methyl syringate selectively activated hTRPA1 (EC(50) = 507.4 μM), but not hTRPV1. Although methyl syringate had a higher EC(50) compared with allyl isothiocyanate (EC(50) = 7.4 μM) and cinnamaldehyde (EC(50) = 22.2 μM), the present study provides evidence that methyl syringate from K. pictus is a specific and selective activator of hTRPA1.
Abstract Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes. Antioxid. Redox Signal. 00, 000-000.
Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.
In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies,
for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various
age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which
polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general
xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously
demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity
in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes,
and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death.
In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial
role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations
of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and
by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated
that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction.
These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against
cognitive decline.
In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.
Mitochondria are a principal site for generation of reactive oxygen species (ROS) in the heart. Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1 alpha) plays an important role in regulating mitochondrial biogenesis and myocardial metabolism, but whether PGC-1 alpha can simultaneously upregulate myocardial mitochondrial antioxidants has not been studied. In the present study, we examined the effect of PGC-1 alpha deficiency (PGC-1 alpha(-/-)) on oxidative stress and expression of a group of mitochondrial antioxidants in normal hearts and in hearts exposed to chronic systolic pressure overload produced by transverse aortic constriction (TAC). We found that PGC-1 alpha(-/-) caused moderate but significant decreases of myocardial mitochondrial antioxidant enzymes such as SOD2, and thioredoxin (Trx2), but had no effect on expression of myocardial oxidative stress markers and left ventricular (LV) function under basal conditions. However, in response to TAC for 6 weeks, PGC-1 alpha(-/-) mice showed greater increases of myocardial oxidative stress markers 3'-nitrotyrosine and 4-hydroxynonenal, more severe LV hypertrophy and dilatation, pulmonary congestion, and a greater reduction of LV fractional shortening and dP/dt(max) than did wild-type hearts. SOD mimetic MnTMPyP treatment (6 mg/kg/day) significantly attenuated TAC-induced LV hypertrophy and dysfunction in PGC-1 alpha(-/-) mice. These data indicate that PGC-1 alpha plays an important role in regulating expression of myocardial mitochondrial antioxidants SOD2 and Trx2 and in protecting hearts against TAC-induced myocardial oxidative stress, hypertrophy, and dysfunction.
Dietary polyphenols represent a wide variety of compounds that occur in fruits,vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They aremostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins andphenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis,anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascularprotection, improvement of the endothelial function, as well as inhibition of angiogenesisand cell proliferation activity. Most of these biological actions have been attributed to theirintrinsic reducing capabilities. They may also offer indirect protection by activatingendogenous defense systems and by modulating cellular signaling processes such asnuclear factor-kappa B (NF-úB) activation, activator protein-1(AP-1) DNA binding,glutathione biosynthesis, phosphoinositide 3 (PI3)-kinase/protein kinase B (Akt) pathway,mitogen-activated protein kinase (MAPK) proteins [extracellular signal-regulated proteinkinase (ERK), c-jun N-terminal kinase (JNK) and P38 ] activation, and the translocationinto the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2). This paper covers themost recent literature on the subject, and describes the biological mechanisms of action andprotective effects of dietary polyphenols.
The antistaphylococcal activity against methicillin-susceptible and -resistant Staphylococcus aureus as well as metabolite profiling of manuka honey, before and after in vitro simulated gastric (GD), and gastroduodenal digestion (GDD) were investigated. Undigested manuka honey showed antibacterial activity against all the tested strains. GD sample showed no activity against S. aureus, while GDD honey showed an antistaphyloccoccal activity which was slightly reduced in comparison with undigested sample. To explain these results, methylglyoxal (MGO), to which is ascribed most of the antibacterial activity of MH, was submitted to in vitro simulated GD and GDD. After digestion, MGO showed antibacterial activity at concentrations definitively higher than those registered in digested MH samples. This results showed that the antistaphylococcal activity registered after digestion cannot be ascribed to MGO. Thus, the metabolite analysis, carried out using an explorative untargeted NMR-based approach and a targeted RP-HPLC-PAD-ESI-MSn analysis focused on bio-active substances, was use to highlight the chemical modifications occurring after digestion. The results showed that 1) the level of MGO decreases, 2) the content of aromatic compounds, such as leptosin and methyl syringate, markers of manuka honey, was stable under gastric and gastroduodenal conditions, whereas 3) the levels of acetic and lactic acids increase especially after gastroduodenal digestion. Overall, the results obtained from chemical analysis provide the explanation of the registered antibacterial activity observed after gastroduodenal digestion.
Objective:
To investigate the effect of 66% Manuka honey gel on the concentrations of transforming growth factor (TGF)-β1 and TGF-β3, bacterial counts and histomorphology during healing of contaminated equine distal limb wounds.
Methods:
In this experimental study of 10 Standardbred horses, five full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus and six similar wounds were created on the contralateral metacarpus. Wounds were assigned to three groups: non-contaminated control wounds; contaminated control wounds; contaminated wounds treated daily with 1 mL Manuka honey gel topically for 10 days. For the contaminated wounds, faeces were applied for 24 h after wound creation. In five horses wounds were bandaged and in the other five horses wounds were left without a bandage. Biopsies were taken on days 1, 2, 7 and 10 after wounding to evaluate the effects of Manuka honey gel, wound contamination and bandaging on TGF-β1 and TGF-β3 concentrations, aerobic and anaerobic bacterial counts, and histomorphology.
Results:
Manuka honey gel had no significant effect on TGF-β1 and TGF-β3 concentrations or wound bacterial counts. Manuka honey gel decreased wound inflammation (days 7, 10), increased angiogenesis (days 2, 7, 10), increased fibrosis and collagen organisation (day 7) and increased epithelial hyperplasia (days 7, 10).
Conclusions:
Treatment with Manuka honey gel resulted in a more organised granulation tissue bed early in wound repair, which may contribute to enhanced healing of equine distal limb wounds.
Our recent study demonstrated that pinocembrin (PB), the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl-4-phenylpyridinium (MPP(+))-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB increased heme oxygenase-1 (HO-1) expression, which conferred protection against MPP(+)-induced cytotoxicity, because the inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of PB. PB induced the phosphorylation of ERK1/2, and its cytoprotective effect was abolished by ERK1/2 inhibitors. Meanwhile, we have shown that MPP(+) induce the expression in a concentration-dependent manner in SH-SY5Y cells, which was further enhanced by PB. Taken together, the results suggest that PB enhances HO-1 expression to suppress MPP(+)-induced oxidative damage via ERK1/2 signaling pathways. These results revealed the mechanisms of PB enhances HO-1 expression,and contribute to shed some light on the mechanisms whereby PB inhibit the MPP(+)-induced neurotoxicity. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.
Objective
To investigate the effect of activated protein C (APC) on second intention healing of distal limb wounds in horses.Methods
In this experimental study of eight Standardbred geldings, six full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus (biopsy limb) and five similar wounds were created on the contralateral metacarpus (photographed limb). Three wounds on the biopsy limb were treated topically with 190 µg APC on days 1, 3, 6 and 9, while the remaining three wounds were untreated (control). One treated and one control wound were biopsied on days 4, 7 and 11 for histopathology. Wounds on the photographed limb were treated with either 66% Manuka honey gel, a commercial antibiotic ointment (bacitracin–neomycin–polymixin B ointment; BNP) or petrolatum daily throughout healing, treated on days 1,3,6 and 9 with 190 µg APC or left untreated. These wounds were digitally photographed and the wound area measured on day 1, then weekly until day 49. Overall time to healing was recorded.ResultsThere was no effect of APC on wound size, the rate of healing or the overall time to heal. However, compared with control wounds, histological scoring demonstrated enhanced epithelialisation (day 4) and angiogenesis (day 11). Wound healing variables for wounds treated with APC, Manuka honey gel and control wounds were not different and the variables for wounds treated with BNP and petrolatum demonstrated delayed healing.Conclusion
The improvements in histological scores in APC-treated wounds suggest further study into the effect of APC on second intention wound healing in horses is warranted.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been reported to have anti-inflammatory and antioxidant activity. This study was designed to evaluate the inhibitory effects of pinocembrin on inflammatory mediators production in LPS-stimulated BV2 microglial cells. The results showed that pinocembrin dose-dependently inhibited LPS-induced inflammatory mediators TNF-α, IL-1β, NO and PGE2 production. Pinocembrin also inhibited LPS-induced iNOS and COX-2 expression. Moreover, pinocembrin inhibited LPS-induced PI3K, Akt phosphorylation, and NF-κB activation, which were required for inflammatory mediators production. Furthermore, treatment of pinocembrin induced nuclear translocation of Nrf2 and expression of HO-1. In conclusion, our data indicated that pinocembrin inhibited LPS-induced inflammatory mediators production by suppressing PI3K/Akt/NF-κB signaling pathway.
Copyright © 2015. Published by Elsevier B.V.
This study investigated the neuroprotective effects of (2R,3S)-pinobanksin-3-cinnamate (PNC) in rats with occlusion-damaged bilateral common carotid arteries. Administration with PNC (5 and 10 mg/kg/day) for 5 weeks significantly improved the behavioral performance of rats with vascular dementia, as showed in the Morris water maze test by shortening the escape latency and latency of crossing, completing more platform crossings, as well as spending more time in the target zone. Further evaluations found that PNC could markedly decrease malondialdehyde levels, enhance superoxide dismutase activity and glutathione levels, and decrease the release of cytochrome c as well as the activities of caspases. Moreover, PNC increased Nrf2 and anti-apoptotic bcl-2 protein expression, while Nox1 and pro-apopotic bax protein expression was decreased. PNC may exert its neuroprotective effects through counteracting oxidative stress and has the potential to treat vascular dementia.
Background:
Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing.
Objectives:
The objective of this review was to assess the effects of honey compared with alternative wound dressings and topical treatments on the of healing of acute (e.g. burns, lacerations) and/or chronic (e.g. venous ulcers) wounds.
Search methods:
For this update of the review we searched the Cochrane Wounds Group Specialised Register (searched 15 October 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9); Ovid MEDLINE (1946 to October Week 1 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October 2014); Ovid EMBASE (1974 to 13 October 2014); and EBSCO CINAHL (1982 to 15 October 2014).
Selection criteria:
Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint.
Data collection and analysis:
Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. All data have been subsequently checked by two more authors.
Main results:
We identified 26 eligible trials (total of 3011 participants). Three trials evaluated the effects of honey in minor acute wounds, 11 trials evaluated honey in burns, 10 trials recruited people with different chronic wounds including two in people with venous leg ulcers, two trials in people with diabetic foot ulcers and single trials in infected post-operative wounds, pressure injuries, cutaneous Leishmaniasis and Fournier's gangrene. Two trials recruited a mixed population of people with acute and chronic wounds. The quality of the evidence varied between different comparisons and outcomes. We mainly downgraded the quality of evidence for risk of bias, imprecision and, in a few cases, inconsistency.There is high quality evidence (2 trials, n=992) that honey dressings heal partial thickness burns more quickly than conventional dressings (WMD -4.68 days, 95%CI -5.09 to -4.28) but it is unclear if there is a difference in rates of adverse events (very low quality evidence) or infection (low quality evidence).There is very low quality evidence (4 trials, n=332) that burns treated with honey heal more quickly than those treated with silver sulfadiazine (SSD) (WMD -5.12 days, 95%CI -9.51 to -0.73) and high quality evidence from 6 trials (n=462) that there is no difference in overall risk of healing within 6 weeks for honey compared with SSD (RR 1.00, 95% CI 0.98 to 1.02) but a reduction in the overall risk of adverse events with honey relative to SSD. There is low quality evidence (1 trial, n=50) that early excision and grafting heals partial and full thickness burns more quickly than honey followed by grafting as necessary (WMD 13.6 days, 95%CI 9.82 to 17.38).There is low quality evidence (2 trials, different comparators, n=140) that honey heals a mixed population of acute and chronic wounds more quickly than SSD or sugar dressings.Honey healed infected post-operative wounds more quickly than antiseptic washes followed by gauze and was associated with fewer adverse events (1 trial, n=50, moderate quality evidence, RR of healing 1.69, 95%CI 1.10 to 2.61); healed pressure ulcers more quickly than saline soaks (1 trial, n= 40, very low quality evidence, RR 1.41, 95%CI 1.05 to 1.90), and healed Fournier's gangrene more quickly than Eusol soaks (1 trial, n=30, very low quality evidence, WMD -8.00 days, 95%CI -6.08 to -9.92 days).The effects of honey relative to comparators are unclear for: venous leg ulcers (2 trials, n= 476, low quality evidence); minor acute wounds (3 trials, n=213, very low quality evidence); diabetic foot ulcers (2 trials, n=93, low quality evidence); Leishmaniasis (1 trial, n=100, low quality evidence); mixed chronic wounds (2 trials, n=150, low quality evidence).
Authors' conclusions:
It is difficult to draw overall conclusions regarding the effects of honey as a topical treatment for wounds due to the heterogeneous nature of the patient populations and comparators studied and the mostly low quality of the evidence. The quality of the evidence was mainly downgraded for risk of bias and imprecision. Honey appears to heal partial thickness burns more quickly than conventional treatment (which included polyurethane film, paraffin gauze, soframycin-impregnated gauze, sterile linen and leaving the burns exposed) and infected post-operative wounds more quickly than antiseptics and gauze. Beyond these comparisons any evidence for differences in the effects of honey and comparators is of low or very low quality and does not form a robust basis for decision making.
The flavonoid components of New Zealand mānuka (Leptospermum scoparium) honey have been quantified in a series of 31 honeys of varying non-peroxide antibacterial activity to clarify discrepancies between previous studies reported in the literature. Total flavonoid content was 1.16mg/100g honey. The principal flavonoids present were pinobanksin, pinocembrin, luteolin and chrysin and together these represented 61% of the total flavonoid content. 1, 2-formyl-5-(2-methoxyphenyl)-pyrrole, which was weakly correlated with the non-peroxide antibacterial activity, was isolated from the flavonoid fraction and separately synthesised. 1 did not display inhibitory activity against Staphylococcus aureus in vitro and thus the origin of the correlation, which is still unknown, is not a direct contribution.
Ethnopharmacological relevance:
Preparations derived from bulbs of various Lilium species have been used to promote the healing of skin abrasions, sores and burns and to aid in healing wounds in Traditional Chinese and Greco-Roman Medicine.
Aim of the study:
To evaluate fractionated Easter lily bulb extracts and their steroidal glycosides (1-5) for the promotion of dermal fibroblast migration in vitro, a model for the early events in wound healing.
Materials and methods:
An activity-guided screening approach was used by coupling sequential solvent extraction, gel permeation chromatography (GPC), and semi-preparative reverse-phase high performance liquid chromatography (RP-HPLC) with an in vitro dermal fibroblast migration assay. Cytotoxicity was evaluated with methyl thiazole tetrazolium (MTT). To gain insight into the mode of action of the steroidal glycosides, nitric oxide (NO) production, and expression of genes for transforming growth factor beta-1 (TGF-β) and its receptors were evaluated.
Results:
Fractionated bulb extracts and the two isolated steroidal glycoalkaloids (1) and (2) induced NO production and TGF-β receptor I mRNA expression in fibroblast cell culture. In a cytotoxicity assay, steroidal glycosides (1) and (3) had IC50 values of 8.2 and 8.7 µM, but the natural acetylation of the C-6″' hydroxy of the terminal glucose unit in (2) resulted in a 3-fold decrease in cell cytotoxicity when compared with (1). Results from the dermal fibroblast migration assay revealed that the steroidal glycoalkaloids (1) and (2), and the furostanol saponin (3) promoted fibroblast migration from the range of 23.7±5.7 to 37.7±5.1%, as compared with the control.
Conclusion:
Collectively, our data demonstrate that the steroidal glycosides present in Easter lily bulbs induce, at least in part, the observed dermal fibroblast migration activity of the bulb extracts. This is the first evidence that steroidal glycosides from Lilium longiflorum may potentially play a role in the wound healing process and may provide a scientific basis for the historical use of lily bulbs for this purpose.
The term "mitochondrial permeability transition" (MPT) refers to an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate mitochondrial outer membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade as well as of caspase-independent cell death mechanisms. MPT appears to be mediated by the opening of the so-called "permeability transition pore complex" (PTPC), a poorly characterized and versatile supramolecular entity assembled at the junctions between the inner and outer mitochondrial membranes. In spite of considerable experimental efforts, the precise molecular composition of the PTPC remains obscure and only one of its constituents, cyclophilin D (CYPD), has been ascribed with a crucial role in the regulation of cell death. Conversely, the results of genetic experiments indicate that other major components of the PTPC, such as voltage-dependent anion channel (VDAC) and adenine nucleotide translocase (ANT), are dispensable for MPT-driven MOMP. Here, we demonstrate that the c subunit of the FO ATP synthase is required for MPT, mitochondrial fragmentation and cell death as induced by cytosolic calcium overload and oxidative stress in both glycolytic and respiratory cell models. Our results strongly suggest that, similar to CYPD, the c subunit of the FO ATP synthase constitutes a critical component of the PTPC.
The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
The historical and current literature reports the successful use of honey to manage a diversity of wound aetiologies. However, only in the last 40 years is research on its mode of action and contribution to wound healing being investigated. The challenge of managing chronic non healing wounds generated interest in researching non standard therapies. The aims of the study were to gain insight into the practical use of Manuka honey in wound management. The objective was to test the feasibility of further rigorous research into the use of honey in the management of chronic wounds. Instrumental case series were used to examine the use of Manuka honey in eight cases of leg ulceration. To collect the necessary data, photographs, acetate tracings, data monitoring and patient comments and observations were used to add greater reliability and validity to the findings. The wounds were dressed weekly with Manuka honey. The results obtained showed three males and five females with ulceration of different aetiologies were studied. A mean initial wound size for all wounds of 5·62 cm2 was obtained. At the end of four-week treatment period, the mean size was 2·25 cm2. Odour was eliminated and pain reduced. The conclusions drawn were that the use of Manuka honey was associated with a positive wound-healing outcome in these eight cases. Arterial wounds showed minimal improvement only.
Apitherapy has become the focus of attention as a form of folk and preventive medicine for treating certain conditions and diseases as well as promoting overall health and well-being. In apitherapy, honey is the therapeutic agent used for dressing surgical wounds, burns or skin ulcers, as well as for dyspepsia, peptic ulcer, etc., because of its antioxidant activity. Therefore, it is important to determine the antioxidants in honey by analytical techniques. In the present study, the antioxidant activities of honeys from different floral sources were investigated by electron spin resonance (1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2/NaOH/DMSO scavenging systems), liquid chromatography with coulometric array detection (LC-ED), and liquid chromatography with electrospray mass spectrometry (LC-MS). The antioxidant activities of some unifloral honeys (acacia, Chinese milk vetch, buckwheat and manuka) were evaluated using the radical scavenging systems. It was shown that DPPH radical scavenging activity was significantly different among the honeys, with buckwheat and manuka honeys having significantly higher scavenging activity than acacia honey. In addition, only manuka honey had specific scavenging activity for superoxide anion radicals. The compound responsible for this activity in manuka honey was identified by LC-ED and LC-MS. Careful examination of the LC-ED chromatographic patterns of manuka and other honey samples revealed a distinct peak in the chromatogram of manuka honey to be methyl syringate (MSYR). The radical scavenging activity of MSYR was specific for superoxide anion radicals, similar to the case of manuka honey. Copyright © 2005 Society of Chemical Industry
Many commercial and household products such as lubricants, cosmetics, plastics, and paint contain phthalates, in particular bis-(2-ethyhexyl)-phthalate (DEHP). As a consequence, phthalates have been found in a number of locations and foods (streambeds, household dust, bottled water and dairy products). Epidemiological and animal studies analysing phthalate exposure in males provide evidence of degradation in sperm quality, associated to an increase in the incidence of genital birth defects and testicular cancers. In the testis, spermatogenesis is maintained throughout life by a small number of spermatogonial stem cells (SSCs) that self-renew or differentiate to produce adequate numbers of spermatozoa. Disruption or alteration of SSC self-renewal induce decreased sperm count and sperm quality, or may potentially lead to testicular cancer. GDNF, or glial cell-line-derived neurotrophic factor, is a growth factor that is essential for the self-renewal of SSCs and continuous spermatogenesis. In the present study, the SSC-derived cell line C18-4 was used as a model for preliminary assessment of the effects of mono-(2-ethylhexyl)-phthalate (MEHP, main metabolite of DEHP) on spermatogonial stem cells. Our data demonstrate that MEHP disrupts one of the known GDNF signalling pathways in these cells. MEHP induced a decrease of C18-4 cell viability in a time- and dose-dependent manner, as well as a disruption of ERK1/2 activation but not of SRC signalling. As a result, we observed a decrease of expression of the transcription factor FOS, which is downstream of the GDNF/ERK1/2 axis in these cells. Taken together, our data suggest that MEHP exposure affects SSC proliferation through inhibition of specific signalling molecules.
As a preliminary study, we have found that honey from manuka (Leptospermum scoparium) in New Zealand inhibits myeloperoxidase (MPO) activity. In this study, using a chromatographic technique, we isolated two active compounds for MPO-inhibition from manuka honey. One is methyl syringate (MSYR), and the other was identified as a novel glycoside of MSYR, methyl syringate 4-O-β-D-gentiobiose, which has been named "leptosin" after the genus Leptospermum . The amount of the glycoside ranged from 0.2 to 1.2 μmol/g honey. Leptosin was only found in honeys from the Oceania region, and abundantly in manuka honey including jelly bush honey from Leptospermum polygalifolium in Australia. Therefore, leptosin may be a good chemical marker for manuka honey. Interestingly, the concentration of leptosin in manuka honey was positively correlated with the unique manuka factor (UMF) value, which is expressed as phenol equivalents of its bactericidal activity.
Prospective, observational study of 20 spinal cord-injured (SCI) patients with chronic pressure ulcers (PUs) using Medihoney.
To determine the effects of Medihoney by bacterial growth, wound size and stage of healing in PUs.
We treated 20 SCI adult patients with chronic PUs using Medihoney. In all, 7 patients (35%) were female, and 13 (65%) were male. The average patient age was 48.7 years (30-79). In all, 6 patients (30%) were tetraplegic and 14 (70%) were paraplegic. Also, 5 patients (25%) had grade IV ulcers and 15 patients (75%) had grade III ulcers according to the National Pressure Ulcer Advisory Panel.
After 1 week of treatment with Medihoney, all swabs were void of bacterial growth. Overall 18 patients (90%) showed complete wound healing after a period of 4 weeks, and the resulting scars were soft and elastic. No negative effects were noted from the treatment using Medihoney. No blood sugar level derailment was documented.
The medical-honey approach to wound care must be part of a comprehensive conservative surgical wound-care concept. Our study indicates the highly valuable efficacy of honey in wound management and infection control as measured by bacterial growth, wound size and healing stage.
AMPK (AMP-activated protein kinase) is a key regulator of cellular energy because of its capacity to detect changes in the concentration of AMP. Recent evidence, however, indicates the existence of alternative mechanisms of activation of this protein. Mitochondrial ROS (reactive oxygen species), generated as a result of the interaction between nitric oxide and mitochondrial cytochrome c oxidase, activate AMPKalpha1 in HUVECs (human umbilical-vein endothelial cells) at a low oxygen concentration (i.e. 3%). This activation is independent of changes in AMP. In the present study we show, using HUVECs in which AMPKalpha1 has been silenced, that this protein is responsible for the expression of genes involved in antioxidant defence, such as manganese superoxide dismutase, catalase, gamma-glutamylcysteine synthase and thioredoxin. Furthermore, peroxisome proliferator-activated-coactivator-1, cAMP-response-element-binding protein and Foxo3a (forkhead transcription factor 3a) are involved in this signalling pathway. In addition, we show that silencing AMPKalpha1 in cells results in a reduced mitochondrial and eNOS (endothelial NO synthase) content, reduced cell proliferation, increased accumulation of ROS and apoptosis. Thus AMPKalpha1 in HUVECs regulates both their mitochondrial content and their antioxidant defences. Pharmacological activation of AMPKalpha1 in the vascular endothelium may be beneficial in conditions such as metabolic syndrome, Type 2 diabetes and atherosclerosis, not only because of its bioenergetic effects but also because of its ability to counteract oxidative stress.
With the objective of finding floral markers for the determination of the botanical origin of acacia (robinia) honey, the phytochemicals present in nectar collected from Robinia pseudacacia flowers were analyzed by high-performance liquid chromatography-tandem mass spectrometry. Eight flavonoid glycosides were detected and characterized as kaempferol combinations with rhamnose and hexose. Acacia honey produced in the same location where the nectar was collected contained nectar-derived kaempferol rhamnosides. This is the first time that flavonoid glycosides have been found as honey constituents. Differences in the stability of nectar flavonoids during honey elaboration and ripening in the hive were shown to be due to hydrolytic enzymatic activity and to oxidation probably related to hydrogen peroxide (glucose-oxidase) activity. Acacia honeys contained propolis-derived flavonoid aglycones (468-4348 microg/100 g) and hydroxycinnamic acid derivatives (281-3249 microg/100 g). In addition, nectar-derived kaempferol glycosides were detected in all of the acacia honey samples analyzed (100-800 microg/100 g). These flavonoids were not detected in any of the different honey samples analyzed previously from different floral origins other than acacia. Finding flavonoid glycosides in honey related to floral origin is particularly relevant as it considerably enlarges the number of possible suitable markers to be used for the determination of the floral origin of honeys.
The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.
A simple and sensitive method for the direct measurement of lipid peroxides in lipoprotein and liposomes is described. The method is based on the principle of the rapid peroxide-mediated oxidation of Fe2+ to Fe3+ under acidic conditions. The latter, in the presence of xylenol orange, forms a Fe(3+)-xylenol orange complex which can be measured spectrophotometrically at 560 nm. Calibration with standard peroxides, such as hydrogen peroxide, linoleic hydroperoxide, t-butyl hydroperoxide, and cumene hydroperoxide gives a mean apparent extinction coefficient of 4.52 x 10(4) M-1 cm-1 consistent with a chain length of approximately 3 for ferrous ion oxidation by hydroperoxides. Endoperoxides are less reactive or unreactive in the assay. The assay has been validated in the study of lipid peroxidation of low density lipoprotein and phosphatidyl choline liposomes. By pretreatment with enzymes known to metabolize peroxides, we have shown that the assay measures lipid hydroperoxides specifically. Other methods for measuring peroxidation, such as the assessment of conjugated diene, thiobarbituric acid reactive substances and an iodometric assay have been compared with the ferrous oxidation-xylenol orange assay.
Publisher Summary This chapter discusses methods to determine carbonyl content in oxidatively modified proteins. The methods described are (1) reduction of the carbonyl group to an alcohol with tritiated borohydride; (2) reaction of the carbonyl group with 2,4-dinitrophenylhydrazine to form the 2,4-dinitrophenylhydrazone; (3) reaction of the carbonyl with fluorescein thiosemicarbazide to form the thiosemicarbazone; and (4) reaction of the carbonyl group with fluorescein amine to form a Schiff base followed by reduction to the secondary amine with cyanoborohydride. Van Poelje and Snell have also quantitated protein-bound pyruvoyl groups through formation of a Schiff base with p-aminobenzoic acid followed by reduction with cyanoborohydride. Although a systematic investigation has not appeared, this method should also be useful in detecting other protein-bound carbonyl groups. Carbonyl content of proteins is expressed as moles carbonyl/mole subunit for purified proteins of known molecular weight. For extracts, the results may be given as nanomoles carbonyl/milligram protein. For a protein having a molecular weight of 50,000, a carbonyl content of 1 mol carbonyl/mol protein corresponds to 20 nmol carbonyl/mg proteins.
A simple, automated test measuring the ferric reducing ability of plasma, the FRAP assay, is presented as a novel method for assessing "antioxidant power." Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form. FRAP values are obtained by comparing the absorbance change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration. Absorbance changes are linear over a wide concentration range with antioxidant mixtures, including plasma, and with solutions containing one antioxidant in purified form. There is no apparent interaction between antioxidants. Measured stoichiometric factors of Trolox, alpha-tocopherol, ascorbic acid, and uric acid are all 2.0; that of bilirubin is 4.0. Activity of albumin is very low. Within- and between-run CVs are <1.0 and <3.0%, respectively, at 100-1000 micromol/liter. FRAP values of fresh plasma of healthy Chinese adults: 612-1634 micromol/liter (mean, 1017; SD, 206; n = 141). The FRAP assay is inexpensive, reagents are simple to prepare, results are highly reproducible, and the procedure is straightforward and speedy. The FRAP assay offers a putative index of antioxidant, or reducing, potential of biological fluids within the technological reach of every laboratory and researcher interested in oxidative stress and its effects.
The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and
cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis,
and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details
of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to
show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
To determine the sensitivity to honey of Gram-positive cocci of clinical significance in wounds and demonstrate that inhibition is not exclusively due to osmotic effects.
Eighteen strains of methicillin-resistant Staphylococcus aureus and seven strains of vancomycin-sensitive enterococci were isolated from infected wounds and 20 strains of vancomycin-resistant enterococci were isolated from hospital environmental surfaces. Using an agar incorporation technique to determine the minimum inhibitory concentration (MIC), their sensitivity to two natural honeys of median levels of antibacterial activity was established and compared with an artificial honey solution. For all of the strains tested, the MIC values against manuka and pasture honey were below 10% (v/v), but concentrations of artificial honey at least three times higher were required to achieve equivalent inhibition in vitro. Comparison of the MIC values of antibiotic-sensitive strains with their respective antibiotic-resistant strains demonstrated no marked differences in their susceptibilities to honey.
The inhibition of bacteria by honey is not exclusively due to osmolarity. For the Gram-positive cocci tested, antibiotic-sensitive and -resistant strains showed similar sensitivity to honey.
A possible role for honey in the treatment of wounds colonized by antibiotic-resistant bacteria is indicated.
The antioxidant properties of six medical herbs used in the traditional Paraguayan medicine were studied using free radical-generating systems. The methanol extracts from Aristolochia giberti, Cecropia pachystachya, Eugenia uniflora, Piper fulvescens, Schinus weinmannifolia and Schinus terebinthifolia protected against enzymatic and non-enzymatic lipid peroxidation in microsomal membranes of rat. C. pachystachya, E. uniflora, S. weinmannifolia and S. terebinthifolia showed the highest scavenging activity on the superoxide and DPPH radicals.