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Reassessment of antioxidant activity of arbutin: Multifaceted evaluation using five antioxidant assay systems

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Abstract

Arbutin, a practically used skin-lightening agent, has been reported to possess a weak antioxidant activity compared to that of its precursor, hydroquinone. However, its antioxidant activity has not been systematically evaluated. Hence, this study reassessed its activity using five assay systems. Assays were first performed using model radicals, DPPH radical and ABTS(*+). Arbutin showed weak DPPH radical-scavenging activity compared to that of hydroquinone, but showed strong ABTS(*+)-scavenging activity. Its activity by ORAC assay was then evaluated using a physiologically relevant peroxyl radical. Arbutin exerted weak but long-lasting radical-scavenging activity and showed totally the same antioxidant activity as that of hydroquinone. Finally, it was shown that, in two cell-based antioxidant assays using erythrocytes and skin fibroblasts, arbutin exerted strong antioxidant activity comparable or even superior to that of hydroquinone. These findings indicate that the antioxidant activity of arbutin may have been under-estimated and suggest that it acts as a potent antioxidant in the skin.

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... Due to its (mildly) anti-microbial, anti-oxidant, and anti-inflammatory activity, it is also widely used in the cosmetic and healthcare industries worldwide, and is also of relevance in the food industry [1][2][3][4][5][6][7][8][9][10][11][12]. For example, since arbutin inhibits the melanogenesis process by the inhibition of tyrosinase, it is used as a depigmenting agent on skin, preventing and eliminating the growth of dark spots [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. A possible mechanism of tyrosinase-inhibition by arbutin has been proposed on the basis of molecular dynamics (MD) computations, leading to the identification of crucial protein-arbutin interactions (Figure 2), which are different from those exhibited by other inhibitors [11]. ...
... Due to its (mildly) anti-microbial, anti-oxidant, and antiinflammatory activity, it is also widely used in the cosmetic and healthcare industries worldwide, and is also of relevance in the food industry [1][2][3][4][5][6][7][8][9][10][11][12]. For example, since arbutin inhibits the melanogenesis process by the inhibition of tyrosinase, it is used as a depigmenting agent on skin, preventing and eliminating the growth of dark spots [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. A possible mechanism of tyrosinaseinhibition by arbutin has been proposed on the basis of molecular dynamics (MD) computations, leading to the identification of crucial protein-arbutin interactions (Figure 2), which are different from those exhibited by other inhibitors [11]. ...
... It has been reported that arbutin inhibits tyrosinase-activity without influencing its biosynthesis in human melanocyte cultures [18,19]. Recent studies on biological effects of arbutin have focused on the reassessment of its antioxidant activity [15] and its function as an attenuator of LPS-induced lung injury via the Sirt1/Nrf2/NF-kBp65 pathway [20]. ...
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Arbutin (also called β-arbutin) is a natural product occurring in the leaves of a variety of different plants, the bearberries of the Ericaceae and Saxifragaceae families being prominent examples. It is a β-glucoside derived from hydroquinone (HQ; 1,4-dihydroxybenzene). Arbutin has been identified in traditional Chinese folk medicines as having, inter alia, anti-microbial, anti-oxidant, and anti-inflammatory properties that useful in the treatment of different ailments including urinary diseases. Today, it is also used worldwide for the treatment of skin ailments by way of depigmenting, which means that arbutin is a component of many products in the cosmetics and healthcare industries. It is also relevant in the food industry. Hundreds of publications have appeared describing the isolation, structure determination, toxicology, synthesis, and biological properties of arbutin as well as the molecular mechanism of melanogenesis (tyrosinase inhibition). This review covers the most important aspects with special emphasis on the chemical and biocatalytic methods for the production of arbutin.
... Takebayashi et al. examined the antioxidant activity of arbutin compared to that of hydroquinone [143]. Arbutin was a weaker scavenger against 1,1-diphenyl-2-picrylhydrazyl radical and a more potent scavenger against 2,2′-azinobis (3-ethylbenzothiazoline-6sulphonic acid) cation radical compared to hydroquinone. ...
... When arbutin is treated in vivo, its concentration in contact with cells must be maintained at 1 mM or lower, so that beneficial efficacy without the risk of serious side effects can be expected. Studies on the antioxidant activity of arbutin are emerging [143,147]. Arbutin scavenges ROS, such as hydroxyl radicals [144], and activates the Nrf2-ARE pathway enhancing the antioxidant capacity of cells [149]. Arbutin can inhibit ROS-mediated signal transduction in melanocytes and prevent skin hyperpigmentation, like other dietary phenolic compounds [142]. ...
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Arbutin is a compound of hydroquinone and D-glucose, and it has been over 30 years since there have been serious studies on the skin lightening action of this substance. In the meantime, there have been debates and validation studies about the mechanism of action of this substance as well as its skin lightening efficacy and safety. Several analogs or derivatives of arbutin have been developed and studied for their melanin synthesis inhibitory action. Formulations have been developed to improve the stability, transdermal delivery, and release of arbutin, and device usage to promote skin absorption has been developed. Substances that inhibit melanin synthesis synergistically with arbutin have been explored. The skin lightening efficacy of arbutin alone or in combination with other active ingredients has been clinically evaluated. Combined therapy with arbutin and laser could give enhanced depigmenting efficacy. The use of arbutin causes dermatitis rarely, and caution is recommended for the use of arbutin-containing products, especially from the viewpoint that hydroquinone may be generated during product use. Studies on the antioxidant properties of arbutin are emerging, and these antioxidant properties are proposed to contribute to the skin depigmenting action of arbutin. It is hoped that this review will help to understand the pros and cons of arbutin as a cosmetic ingredient, and will lead to future research directions for developing advanced skin lightening and protecting cosmetic products.
... On the other hand, considering that arbutin contained in 0.03 mg/mL was about 0.006 mg/mL, at this concentration arbutin alone produced a weak radical scavenging activity (i.e., 13%). However, as shown by Takebayashi et al., arbutin may show its radical-scavenging effect in a long-lasting manner and therefore its antioxidant activity, evaluated after 15 min, is underestimated [44]. A linear reduction was observed at concentrations of 0.01 and 0.005 mg/mL, with an RSA rate of 55 and 43%, respectively ( Figure 9). ...
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Cutibacterium acnes (C. acnes) is the main causative agent of acne vulgaris. The study aims to evaluate the antimicrobial activity of a natural product, Arctostaphylos uva-ursi leaf extract, against C. acnes. Preliminary chemical–physical characterization of the extract was carried out by means of FT-IR, TGA and XPS analyses. Skin permeation kinetics of the extract conveyed by a toning lotion was studied in vitro by Franz diffusion cell, monitoring the permeated arbutin (as the target component of the extract) and the total phenols by HPLC and UV-visible spectrophotometry, respectively. Antimicrobial activity and time-killing assays were performed to evaluate the effects of Arctostaphylos uva-ursi leaf extract against planktonic C. acnes. The influence of different Arctostaphylos uva-ursi leaf extract concentrations on the biofilm biomass inhibition and degradation was evaluated by the crystal violet (CV) method. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test was used to determine the viability of immortalized human keratinocytes (HaCaT) after exposure to Arctostaphylos uva-ursi leaf extract for 24 and 48 h. Levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α were quantified after HaCaT cells cotreatment with Arctostaphylos uva-ursi leaf extract and heat-killed C. acnes. The minimum inhibitory concentration (MIC) which exerted a bacteriostatic action on 90% of planktonic C. acnes (MIC90) was 0.6 mg/mL. Furthermore, MIC and sub-MIC concentrations influenced the biofilm formation phases, recording a percentage of inhibition that exceeded 50 and 40% at 0.6 and 0.3 mg/mL. Arctostaphylos uva-ursi leaf extract disrupted biofilm biomass of 57 and 45% at the same concentrations mentioned above. Active Arctostaphylos uva-ursi leaf extract doses did not affect the viability of HaCaT cells. On the other hand, at 1.25 and 0.6 mg/mL, complete inhibition of the secretion of pro-inflammatory cytokines was recorded. Taken together, these results indicate that Arctostaphylos uva-ursi leaf extract could represent a natural product to counter the virulence of C. acnes, representing a new alternative therapeutic option for the treatment of acne vulgaris.
... Its chemical formula is C12H16O7 and its molecular weight is 272.25 g/ mol (6) . Arbutin plays an anti-apoptotic role in reducing production of intracellular hydroxyl radicals by scavenging the free radical activity (7,8) . It is also used as a component in skin care products (9) . ...
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Background: Radiation-induced lung injury is a common complication after esophageal, breast, etc. cancer radiotherapy. We aimed to evaluate the radioprotective effect of arbutin on acute radiation-induced lung damage in male rats. Materials and Methods: Fifty-two male Wistar rats were divided into 4 groups: (i) control group (n = 10), (ii) vehicle group (n = 10, received distilled water intraperitoneally (ip)), (iii) X-irradiation only (n=16, chest was irradiated to a single dose of 20 Gy x-rays) and (iv) arbutin + X-irradiation (n=16, 75 mg/kg of arbutin 2 hours before irradiation (ip), and then their chest was exposed to 20 Gy x-rays). For histopathological investigation, 8 animals of each group were sacrificed 8 weeks after treatment and the rest of them were sacrificed 3 months after treatment. Results: The histopathological analysis in 8 weeks after X-irradiation showed that there was a significant increase in inflammatory in X-irradiation only group compared to control group. The administration of arbutin 2 hours prior to X-irradiation significantly reduced inflammation and inflammatory factors such as macrophages, mast cell and neutrophil in arbutin + X-irradiation group compared to X-irradiation only group (P<0.05). The histopathologic investigation performed 3 months after lung irradiation indicated a significant reduction in fibrosis formation in arbutin + X-irradiation group compared to irradiation only group (P<0.05). Localized chest X-irradiation with 20 Gy caused histopathologic damage to the lungs for short -term. Conclusion: Arbutin has a great potential in reducing the histopathologic damage to lung tissue after thoracic irradiation.
... In two cell-based antioxidant analysis using erythrocytes and skin fibroblasts, arbutin was found to exhibit potent antioxidant activity comparable or even superior to that of hydroquinone. 49 In another study conducted; On the protective effects of ARB on streptozotocin (STZ) induced neurotoxicity in rats, it was concluded that ARB has a protective role against STZ-induced memory impairment in the brain and oxidative damage in the hippocampus. 50 In a different literature study; ...
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Background: In the presented study; the Effects of Arbutin (ARB) on the Rat Erythrocyte and serum fatty acid profile which is exposed to potassium bromate (KBrO 3) were investigated. Materials and Methods: In this study, 32 Wistar albino rats weighing 250-300 g were used divided into 4 groups. Groups 1: control, group 2: KBrO 3 (single dose 100 mg / kg gavage), group 3: ARB (50 mg / kg / day (ip) for 5 days), group 4: KBrO 3 + ARB. At the end of the 5 th day, alteration of fatty acid profile in erythrocyte and serum of rats in all groups was examined. Results: Rat serum essential fatty acid; palmitic acid (C16:0), myristic acid (C14:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), erythrocyte major fatty acids; palmitic acid (C16:0), myristic acid (C14:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), arachidic acid (C20:0), eicosenoic acid (C20:1), and lignoceric acid (C24:0). In addition, in our studied serum and erythrocytes; Total monounsaturated fatty acids (MUFA) varied between 8.91 ± 0.53-11.71 ± 2.55 and 33.71 ± 2.12-37.11 ± 2.12, respectively. It was determined that total polyunsaturated fatty acids (PUFA) varied between 5.90 ± 1.29-9.96 ± 1.18 and 14.72 ± 3.66-22.13 ± 4.82, respectively. Conclusion: In our study, alterations in fatty acid contents were observed, and results suggesting that arbutine affects the enzymes involved in Fatty acid metabolism and has an effect on fatty acid amounts.
... Some studies have demonstrated the antioxidant effects of few Turnera species [1,2]. Recently, studies have shown that the genus Turnera contains greater concentrations of arbutin, an important biological compound found in different parts of the plant [3,4]. Though T. subulata is widely used in folk medicine for ages only few research articles are available about its pharmacological and biological properties [5]. ...
Article
Turnera subulata is a substantial medicinal plant used in folk medicine to treat various ailments. The current study was assess the total phenolic and flavonoid contents to evaluate the antioxidant and anti-inflammatory activities of the sequentially extracted T. subulata plant samples. In vitro anti-angiogenic activity was evaluated by chick chorioallantoic membrane (CAM) model for chloroform, ethyl acetate and ethanol extracts. The results obtained revealed that total phenolic content of the chloroform extract (24.13 ± 0.27 mg/g) and total flavonoid content (TFC) of the chloroform extract (22.28 ± 0.40 mg/g) were found to be suggestively higher than the other extracts. A strong antioxidant property was observed for all the six extracts. A study anti-inflammatory activity was observed in chloroform and ethanol extracts, with IC50 ranging from 79 ± 1.01 μg/mL to 81 ± 1.01 μg/mL for protein denaturation assay and from 74 ± 0.11 μg/mL to 76 ± 1.11 μg/mL for HRBC membrane stabilization assay, respectively. The chloroform and ethanol extracts have exhibited good antiangiogenic property. Eventually, these results justified that the chloroform and ethanol extracts of T. subulata with great antioxidant, anti-inflammatory and antiangiogenesis potentials could be promising candidates for the development of a cost effective, potent anticancer drug with minimal side effects.
... Thus, we postulate that Arbutin efficiently scavenges the uncontrolled production of ROS produced by ISO and protects the myocardium from ISO-induced damage. Our results are supported by previous reports which demonstrated the anti-oxidant effect of Arbutin in vitro and in vivo [19,44]. ...
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Arbutin is a glycoside reported for its anti-oxidant, anti-inflammatory and anti-tumor properties. However, the cardioprotective effect of Arbutin is not well established. The study aims to understand the effect of arbutin on isoproterenol (ISO)-induced cardiac hypertrophy in mice. The animals were pretreated with Arbutin for a week and ISO was administered for 10 days and then sacrificed. Cardiac injury markers such as creatinine kinase and lactate dehydrogenase concentrations were measured in the serum. The mRNA expression of cardiac hypertrophy markers namely atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured using qRT-PCR. The levels of pro-inflammatory cytokines TNF-α and IL-6 were quantified by ELISA in isolated tissues and serum. Other tissue anti-oxidant parameters such as GST, GSH, SOD and TBARS were also measured. TUNEL assay was performed to detect apoptosis. Histology studies were performed using H & E and Masson trichome staining. Immunoblot analysis was used to quantify the protein expression of TLR-4 and NF-κB. ISO-alone-treated group showed significant increase in CK-MB, LDH along with increase in hypertrophic markers ANP and BNP, TNF-α and IL-6 levels in serum and tissues and increased cardiomyocyte apoptosis. Anti-oxidant parameters were significantly decreased and TLR-4 and NF-κB protein expression was found to be upregulated in comparison to the control group. Pretreatment with Arbutin-exhibited significant inhibition of TLR-4/NF-κB pathway with decreased levels of pro-inflammatory cytokines and enhanced myocardial anti-oxidant status. Our study demonstrated that pretreatment with Arbutin exhibits marked protective effects on ISO-induced cardiac hypertrophy in mice. Thus, Arbutin may be used as potential pharmacological interventions in the management of cardiac hypertrophy.
... It was reported that the chlorogenic acid was found beneficial against hyperglycemia, and regulated lipid metabolism which was most probably through its antioxidant mediated activity [47,48]. The arbutin and its derivatives, like other phenols, exhibit antioxidant activity [49], and it was also reported that arbutin was a comparable or even superior antioxidant to hydroquinone against the free radicals [50]. Additionally, antioxidant activity of catechins is well established in vitro [51]. ...
Article
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This study aimed to develop a mathematical model for the extraction of Pyrus elaeagrifolia Pallas leaves using the Box–Behnken design, to investigate bioactivity and bacterial β-glucuronidase (GUS) inhibitory potential of the extracts obtained under optimum conditions. Results showed that the mathematical models using extraction temperature, time and ethanol concentration as effective parameters fit the real data well. The optimum extraction conditions to maximize phenolic content and antioxidant activity were found 79.7 and 78.4% ethanol, 74.9 °C, and 45.0 and 35.9 min, respectively. The chlorogenic acid was detected as the major phenolic compound in the chromatographic analysis. The highest antibacterial activity achieved against Staphylococcus aureus. The extracts (150 μg/mL) showed 67.9%, and 75.2% cytotoxic effect on the MCF-7 and A549 cells, respectively, and displayed inhibitory potential against GUS. The antioxidant property together bioactivity makes Pyrus elaeagrifolia Pallas leaves potent source for functional food/food ingredient applications and nutraceutical development.
... In fact, one molecule of arbutin scavenged three molecules of ABTS radical cation, while hydroquinone scavenged two molecules of the same radical cation [91]. The antioxidant activity of arbutin was also determined in other studies by different methods of analysis [92][93][94]. Moreover, some in vitro studies have been conducted and showed the cytotoxic effect [95,96] and the anti-inflammatory properties of arbutin [97,98]. ...
Article
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Some species of the Ericaceae family have been intensively studied because of the beneficial health impact, known since ancient times, of their chemical components. Since most studies focus on the effects of fruit consumption, this review aims to highlight the phenolic components present in the leaves. For this purpose, five species from Ericaceae family (bilberry—Vaccinium myrtillus L., lingonberry—V. vitis-idaea L., bog bilberry—V. uliginosum L., blueberry—V. corymbosum L. and bearberry—Arctostapylos uva-ursi L.) were considered, four of which can be found in spontaneous flora. The chemical composition of the leaves revealed three major phenolic compounds: chlorogenic acid, quercetin and arbutin. The health promoting functions of these compounds, such as antioxidant and anti-inflammatory properties that could have preventive effects for cardiovascular disease, neurodegenerative disorders, cancer, and obesity, have been exemplified by both in vitro and in vivo studies in this review. Furthermore, the importance of bioaccessibility and bioavailability of the phenolic compounds have been summarized. The findings highlight the fact that leaves of some Ericaceae species deserve increased attention and should be studied more profoundly for their biological activities, especially those from spontaneous flora.
... They are known therapeutic agents in diseases such as urinary tract infections 11 and skin hyperpigmentation, 12 and they exhibit anti-inflammatory 13 and antioxidant properties. 14 For the determination of a wide range of phenolics, namely hydroquinone and hydroxycinnamic acid derivatives in plant extracts, including those obtained from Pyrus species, reversed-phase high-performance liquid chromatography (RP-LC) coupled with photodiode-array (PDA) detection has been preferentially used. [15][16][17][18][19][20][21][22][23][24] Some phenolics are known to exhibit specific native fluorescence (FL) that enables a significant reduction in limits of detection (LOD) and quantitation (LOQ) using fluorimetric determination. ...
Article
Dried leaf samples of Pyrus communis L. var. 'Conference' and Pyrus pyrifolia Burm. f. (Nakai) var. 'Shinseiki' were subjected to the successful extraction procedures using various solvents, followed by filtering and/or drying liquid plant preparations under reduced pressure. As a result of this, for each Pyrus leaf sample examined, four dried residues were obtained, including methanolic (EA), ethyl acetate (EC), water (EB), and the residue obtained from aqueous solution (ED). Antiradical activity of these preparations was measured using the ABTS+• assay, and antimicrobial activity was examined using various strains of bacteria and yeasts. The highest antiradical activity was observed for EC from leaves of P. communis var. 'Conference' collected in May, but the highest average antibacterial activity was noted for EC residues from P. pyrifolia var. 'Shinseiki' collected in May. Antibacterial activity positively correlated with concentration of hydroquinone in extracts. No antifungal activity was observed for any extract. In addition, qualitative and quantitative analyses of active polyphenolic components in extracts from Pyrus were performed. Hydroquinone and hydroxycinnamic acid derivatives were analyzed using a new optimized method comprising reversed-phase high-performance liquid chromatography (RP-LC) coupled with simultaneous photodiode-array and fluorescence detection.
... Previous studies suggested that arbutin is a potent antioxidative and cytoprotective agent [21,44]. To assess the antioxidant property of arbutin in demyelination condition, the expression levels of iNOS, HO-1, and Nrf-2 genes were evaluated. ...
Article
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Neuroinflammation, glial activation, and oxidative injury are the main pathological mechanisms of demyelination in multiple sclerosis (MS). Arbutin, a natural polyphenol compound, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has not been studied in the experimental animal models of MS. In the present study, the efficiency of arbutin on lysolecthin (LPC)-induced local demyelination model was investigated. Demyelination was induced by micro-injection of 2 μl LPC (1%) into the rat optic chiasm and the treated group received daily injection of arbutin (50 mg/kg, i.p) during 2 weeks. Visual-evoked potential (VEP) recordings were used to functionally assess the visual pathway. Gene expression analysis was done to evaluate the arbutin effect on the inflammatory, stress oxidative-related mediators, and myelin markers. The myelin-specific staining was performed to assess demyelination and GFAP staining as an astrocyte marker. We found that arbutin significantly reduced P1-latency of VEPs waves and demyelination at 7 and 14 days post-demyelination. Arbutin decreased inflammatory cytokines (IL-1B, IL-17, TNF-α) and iNOS mRNA expression level. In addition, the expression level of anti-inflammatory cytokine (IL-10) and antioxidant mediators (Nrf-2 and HO-1) was enhanced by arbutin treatment. Arbutin increased MBP and Olig2 expression levels in demyelination context. Finally, arbutin attenuated GFAP as an astrocyte marker. Finally, this study demonstrates that arbutin improves functional recovery and myelin repair in the demyelinated optic chiasm through attenuation of inflammation, astrocyte activation, and oxidative stress. These findings might open new promising avenues for treating demyelinating disorders such as multiple sclerosis. Graphical abstract
... For instance, Dong et al. (2005) found that 12 h-pretreatment of the human ECV-304 cells line with 500 lg/L of arbutin had beneficial effects against oxidative damage by H 2 O 2 . Takebayashi et al. (2010) found that arbutin is a potent radical scavenger. Lee and Kim (2012) also reported the antioxidative effects of arbutin in murine microglial BV2 cells. ...
Article
Strawberry tree (Arbutus unedo L.) leaves have long been used in the traditional medicine of the Mediterranean region. One of their most bioactive constituents is the glycoside arbutin, whose presence makes A. unedo suitable as a potential substitute for bearberry [Arctostaphylos uva ursi (L.) Spreng] leaves, an herbal preparation widely used for treating urinary tract infections. The safety and biocompatibility of strawberry tree water leaf extract have not yet been documented well. This study estimated arbutin content in strawberry tree water leaf extract (STE) using high performance liquid chromatography. Furthermore, we performed an in vitro safety assessment of the 24 h exposure to three presumably non-toxic concentrations of standardized STE and arbutin in human peripheral blood lymphocytes using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus cytome assay. The STE was also tested for total antioxidant capacity and lipid peroxidation. At a concentration corresponding to the maximum allowable daily intake of arbutin, the tested extract was not cytotoxic, had a negligible potential for causing primary DNA damage and even hindered micronuclei formation in lymphocytes. It also showed a valuable antioxidant capacity, and did not exert marked lipid peroxidation. These promising results represent a solid frame for further development of STE-based herbal preparations. Although arbutin generally had a low DNA damaging potential, the slowing down of lymphocyte proliferation observed after 24 h of exposure points to a cytostatic effect, which merits further research.
... This activity has found considerable applications in the cosmetic industry as a powerful vegetable-based whitening agent. 8,9 However, arbutin suffers from low bioavailability due to its poor cell membrane penetration. Recently, many studies have indicated that acylation modication of arbutin could increase its antimelanogenesis and antioxidant activities. ...
Article
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Acylation modification of phenol glycosides is currently of great interest due to the improved bioavailability and multiple functions. In this work, mono- or diesters of arbutin, an important phenol glycoside derivative, can be controllably synthesized by using whole-cell biocatalytic systems. Among fourteen microbial strains selected, Candida parapsilosis cells showed the best catalytic activity and high organic solvent tolerance. Compared with the best pure solvent tetrahydrofuran, the use of a binary solvent pyridine-isooctane gave a slightly lower conversion (98.3% vs. 97.2%) and selectivity (85.3% vs. 80.5%) and much higher substrate solubility (37.1 vs. 214.0 mg mL⁻¹), in a 24 h bioconversion of arbutin with a VP-arbutin molar ratio of 15 and whole cell dosage of 30 mg mL⁻¹. The production of various arbutin esters with different fatty acid chain lengths can be realized by using this whole-cell strategy, with the substrate conversion and 6′-regioselectivity of 54.1–98.3% and 83.2–99.0%, respectively.
... Based on analyses of their NMR and mass spectral data, these flavonoids were identified as juglanin (1) [4], astragalin (2) [5], nicotiflorin (3) [6], isoquercetin (4) [7] and apigenin-7-O--glucuronide (5) [7], ( Figure 1). In addition, purification of the n-BuOH extract led to the isolation of an antioxidant phenolic glucoside, arbutin (6) [8][9], as its major component. This is the first report of these phenolic compounds as constituents of A. mahidolae. ...
Article
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Five known flavonoid glycosides namely, juglanin (1), astragalin (2), nicotiflorin (3), isoquercetin (4) and apigenin-7-O-β-glucuronide (5), and a phenolic glucoside, arbutin (6), were isolated for the first time from the leaves of Afgekia mahidolae (Fabaceae). Their structures were elucidated using one- and two-dimensional NMR spectroscopic methods and comparison with the literature. The ability of 1-4 to promote the migration of CCD-1064sk fibroblasts into a scratch-wound area was evaluated. The results indicated that juglanin (1) and nicotiflorin (3) significantly increased the migration of these cells and, hence, supporting the wound healing effect of flavonol glycosides.
... Arbutin is also present in many fruits, vegetables, spices, coffee, tea, as well as in cosmetic products, especially those intended for skin lightening (Blaut et al., 2006;Gillbro and Olsson, 2011;European Medicines Agency, 2012). Results of previous studies suggest that arbutin is potent antioxidative and cytoprotective agent (Takebayashi et al., 2010;Seyfizadeh et al., 2012;Pečivová et al., 2014). During bioactivation process, arbutin is metabolised in the presence of enzyme β-glucosidase to glucose and hydroquinone (Blaut et al., 2006). ...
Article
Ethnopharmacological relevance: Strawberry tree (Arbutus unedo L., Ericaceae) leaves represent a potent source of biologically active compounds and have been used for a long to relieve symptoms of various health impairments and diseases. Two major compounds related to their beneficial activities in animals and humans are arbutin and hydroquinone. Aim of the study: To establish potential benefit/risk ratio associated with daily oral administration of strawberry tree water leaf extract, arbutin and hydroquinone in doses expected to be non-toxic. Materials and methods: We performed a 14-day and a 28-day study on male and female Lewis rats and evaluated main haematological parameters and the effects of treatments on the levels of primary DNA damage in white blood cells (WBC) using the alkaline comet assay. Results: Our findings suggest no significant changes in the haematological parameters following prolonged exposure to strawberry tree water leaf extract, arbutin, and hydroquinone. However, hydroquinone causes increased, and extract as well as arbutin decreased WBC count in male rats compared to control after 14 days of treatment. DNA damage measured in WBC of rats treated with all compounds was below 10% of the DNA in the comet tail, which indicates low genotoxicity. The genotoxic potential of strawberry water leaf extract was within acceptable limits and reflected effects of a complex chemical composition upon DNA. We also observed slight gender- and exposure time- related differences in primary DNA damage in the leukocytes of control and treated rats. Conclusions: Future studies should investigate which doses of strawberry tree water leaf extract would be most promising for the potential use as a substitute for bearberry leaves for treatment of urinary infection.
... Recently, studies have associated positive effects attributed to genus Turnera with higher concentrations of arbutin, a biological compound found in different parts of the plant. [10][11][12] The decrease of cytokine secretion, such as TNF-a, IL-1, and IL-6, observed in treatments with Turnera diffusa or Turnera ulmifolia in different models of in vivo inflammation was reported as positive effects of those plants. 5,7,13,14 Moreover, the antioxidant properties of those extracts were demonstrated through the decreased lipoperoxidation and modulation of antioxidant enzymes such as glutathione peroxidase, superoxide dismutase (SOD), and catalase (CAT) in the liver of CCl4-treated rats. ...
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In South America, particularly in the Northeastern regions of Brazil, Turnera subulata leaf extract is used as an alternative traditional medicine approach for several types of chronic diseases, such as diabetes, hypertension, chronic pain, and general inflammation. Despite its widespread use, little is known about the medicinal properties of the plants of this genus. In this study, we evaluate the antioxidant and anti-inflammatory of T. subulata leaf extract in an in vitro model of inflammation, using lipopolysaccharide-stimulated RAW-264.7 macrophage cell line. We observed that cotreatment with T. subulata leaf extract was able to reduce the oxidative stress in cells due to inflammatory response. More importantly, we observed that the leaf extract was able to directly modulate inflammatory response by altering activity of members of the mitogen-activated protein kinase pathways. Our results demonstrate for the first time that T. subulata have antioxidant and anti-inflammatory properties, which warrant further investigation of the medicinal potential of this species.
... 21 In erythrocytes, arbutin shows long-lasting radical scavenging properties and protects a membrane lipid from oxidative stress in human skin fibroblasts. 22,23 It has antioxidant properties, protects skin against sunburn, is used as whitening agent, and for protection against extreme UV radiation in pharmacological formulations. Arbutin does not cause skin or eye irritation. ...
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Background: Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation. In the present study, the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte (PCE/PCE+NCE) in order to show cell proliferation activity. Methods: Arbutin (50, 100, and 200 mg/kg) was intraperitoneally (ip)administered to NMRI mice two hours before gamma radiation at 2 and 4 gray (Gy). The frequency of micronuclei in 1000 PCEs (MnPCEs) and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA, Tukey HSD test, and t-test. Results: The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE (P<0.001) while reducing PCE/PCE+NCE (P<0.001) compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control (P<0.001). All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor (DRF) showed DRF=1.93 for 2Gy and DRF=2.22 for 4 Gy. Conclusion: Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation.
... Arbutin is known as an antioxidant and depigmenting agent (Lee and Kim, 2012). Arbutin shows long-lasting radical scavenging activity in erythrocytes, as well as in human skin fibroblasts, and protects membrane lipids from oxidative stress (Takebayashi et al., 2010). ...
Article
The aim of this study was to identify and compare phenolic acids, flavan-3-ols and procyanidins, flavonol glycosides, flavones and hydroquinones in different cultivars of pear. Pear fruits (Pyrus communis L.) of ten cultivars ('Bonkreta Williamsa', 'Carola', 'Dicolor', 'Faworytka', 'Hortensia', 'Konferencja', 'Lukasówka', 'Nojabrska', 'Radana' and 'Uta') were used in this study. Sixty-five phenolic compounds, including 26 phenolic acids, 22 flavan-3-ols and procyanidins, 15 flavonols, 1 flavone, and 1 hydroquinone, were determined in the examined samples using the ultra-performance liquid chromatography photodiode detector-quadrupole/time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS) method. Major differences were found in the phenolic profiles of investigated cultivars. The 'Radana' cultivar exhibited the highest total phenolics content (894.9 mg/kg FW) and was characterized by the highest concentration of phenolic acids (503.1 mg/kg FW) and arbutin (70.8 mg/kg FW).
... Although hydroquinone has antioxidative properties, 38 postexercise increases were not related to the increase in FRAP. Dihydroferulic acid increased 3.2-fold with pear ingestion in the cyclists, and this may represent metabolite formation from pear ferulic acid and chlorogenic acid. ...
Article
Bananas and pears vary in sugar and phenolic profiles, and metabolomics was utilized to measure their influence on exercise performance and recovery. Male athletes (N=20) cycled for 75 km while consuming water (WATER), bananas (BAN), or pears (PEAR) (0.6 g carbohydrate/kg each hour) in randomized order. UPLC-MS/MS and the library of purified standards maintained by Metabolon (Durham, NC) were used to analyze metabolite shifts in pre- and post-exercise (0-h, 1.5-h, 21-h) blood samples. Performance times were 5.0% and 3.3% faster during BAN and PEAR versus WATER (P=0.018 and P=0.091, respectively), with reductions in cortisol, IL-10, and total leukocytes, and increases in blood glucose, insulin, and FRAP. Partial Least Square Discriminant Analysis (PLS-DA) showed a distinct separation between trials immediately- (R2Y=0.877, Q2Y=0.457) and 1.5-h-post-exercise (R2Y=0.773, Q2Y=0.441). A total of 107 metabolites (primarily lipid-related) increased more than 2-fold during WATER, with a 48% and 52% reduction in magnitude during BAN and PEAR recovery (P<0.001). Increases in metabolites unique to BAN and PEAR included fructose and fruit constituents, and sulfated phenolics that were related to elevated FRAP. These data indicate that BAN and PEAR ingestion improves 75-km cycling performance, attenuates fatty acid utilization and oxidation, and contributes unique phenolics that augment antioxidant capacity.
... Its chemical formula is C12H16O7 and its molecular weight is 272.25 g/ mol (6) . Arbutin plays an anti-apoptotic role in reducing production of intracellular hydroxyl radicals by scavenging the free radical activity (7,8) . It is also used as a component in skin care products (9) . ...
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Background: Radiation-induced lung injury is a common complication after esophageal, breast, etc. cancer radiotherapy. We aimed to evaluate the radioprotective effect of arbutin on acute radiation-induced lung damage in male rats. Materials and Methods: Fifty-two male Wistar rats were divided into 4 groups: (i) control group (n = 10), (ii) vehicle group (n = 10, received distilled water intraperitoneally (ip)), (iii) X-irradiation only (n=16, chest was irradiated to a single dose of 20 Gy x-rays) and (iv) arbutin + X-irradiation (n=16, 75 mg/kg of arbutin 2 hours before irradiation (ip), and then their chest was exposed to 20 Gy x-rays). For histopathological investigation, 8 animals of each group were sacrificed 8 weeks after treatment and the rest of them were sacrificed 3 months after treatment. Results: The histopathological analysis in 8 weeks after X-irradiation showed that there was a significant increase in inflammatory in X-irradiation only group compared to control group. The administration of arbutin 2 hours prior to X-irradiation significantly reduced inflammation and inflammatory factors such as macrophages, mast cell and neutrophil in arbutin + X-irradiation group compared to X-irradiation only group (P<0.05). The histopathologic investigation performed 3 months after lung irradiation indicated a significant reduction in fibrosis formation in arbutin + X-irradiation group compared to irradiation only group (P<0.05). Localized chest X-irradiation with 20 Gy caused histopathologic damage to the lungs for short -term. Conclusion: Arbutin has a great potential in reducing the histopathologic damage to lung tissue after thoracic irradiation.
... Some studies showed that arbutin has antioxidant activity but not strong as its aglycone [57]. Takebayashi et al. [58] demonstrated that arbutin possessed weak but long-lasting radicals-scavenging effects and strong antioxidant activity comparable or superior to that of its aglycone in two cell-based antioxidant tests using skin fibroblasts and erythrocytes. As reported in several studies, generally the antioxidant activity of phenolic compounds was linked to hydroxyl groups present in their structure [55]. ...
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This study aims at investigating the contribution of two classes of compounds, flavonoids and iridoids, to the bioactivity of Arbutus unedo L. leaves and fruits. The impact of different extraction procedures on phytochemicals content and hypoglycemic, antioxidant, and nitric oxide (NO) inhibitory activities of A. unedo fresh and dried plant materials was investigated. Ellagic acid 4-O-β-D-glucopyranoside, kaempferol 3-O-glucoside, and norbergenin were identified for the first time in this genus by using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS). Three iridoids (gardenoside, geniposide, unedoside) are specifically identified in the leaves. Interestingly, asperuloside was extracted only from dried fruits by ethanol with Soxhlet apparatus. Extracts were screened for their potential antioxidant activities by using the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Activity Power (FRAP), and β-carotene bleaching tests. Based on the Global Antioxidant Score (GAS) calculation, the most promising antioxidant extract was obtained by hydroalcoholic maceration of dried leaves that showed half maximal inhibitory concentration (IC50) of 0.42 and 0.98 μg/mL in ABTS and DPPH assays, respectively. The hypoglycaemic activity was investigated by α-amylase and α-glucosidase inhibition tests. Extracts obtained by ethanol ultrasound extraction of fresh leaves and hydroalcoholic maceration of fresh fruits (IC50 of 19.56 and 28.42 μg/mL, respectively) are more active against α-glucosidase than the positive control acarbose (IC50 of 35.50 μg/mL). Fruit extracts exhibited the highest anti-inflammatory activity.
... Phenolic compounds, including polyphenols, have been shown that decrease amount of ROS and inflammation in various cells. Arbutin, β-D-glucopyranoside, is also a phenolic compound that in some studies have shown its antioxidant and anti-inflammatory effects (Lee & Kim, 2012;Takebayashi et al., 2010). ...
Article
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Increased reactive oxygen species (ROS) along with inflammation are involved in the prostate cancer (PCa). Therefore, this study was conducted to investigate the molecular mechanisms that were affected by arbutin as an antioxidant on prostate cancer cell line; LNCap. The intracellular ROS measurement confirmed that arbutin significantly (p < .05) decreased the ROS levels in a dose‐dependent manner. Detection of cell death profile established that 1,000 μM of arbutin could remarkably induced apoptosis (p < .05), while tert‐butyl hydroperoxide (tBHP) as ROS inducer prompted necrosis. In addition, 1,000 µM of arbutin successfully decreased expressions of IL‐1β and TNF‐α genes (p < .05). Furthermore, evaluation of the IL‐1β protein level showed that arbutin could significantly decrease this cytokine (p < .05). In summary, reduction of ROS along with increasing apoptosis and decreasing expression of pro‐inflammatory genes following arbutin treatment can open new visions in the treatment of prostate cancer using complementary medicine. Practical applications Nowadays, arbutin as a glycosylated hydroquinone is available commercially in both natural and synthetic forms. Arbutin is of interest because of its skin‐lightening effect, and used in cosmetic products for cutaneous hyperpigmentation. Arbutin inhibited tyrosinase in melanocytes competitively. Moreover, arbutin was able to attenuate oxidative stress and, its anti‐inflammatory activities has been established. In addition, arbutin has represented useful activities for suppression of malignant melanoma development. In addition, arbutin exhibits several pharmacological effects, including antimicrobial, antihyperlipidemic, antihyperglycemic, and alpha amylase inhibitory effects. In this study, we showed its effect on prostate cancer in vitro. Therefore, it opens new insights in the complementary medicine that can maintain or improve human health.
... In particular, it is to underline the high levels found for arbutin reported in the literature as a long-lasting radical-scavenger. 40 Poly-unsaturated fatty acids are also natural antioxidants normally found in chia seeds 7 and in our data also in stems and flowers (Tables S3 and S4 in the supporting information). ...
Article
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Background Chia (Salvia hispanica L.) is a functional food from Central America in which interest is rapidly growing due to the many health benefits from the seed. However, when chia is grown at high latitudes, seed yield may be low whereas a high stem biomass and immature inflorescences are produced. Little is known about the chemical composition and the properties of stems and flowers. In this work, the metabolite profile, the antioxidant activity and the total polyphenol content of stems and inflorescences, were evaluated in a factorial experiment with different chia populations (commercial black Chia and long‐day flowering mutants G3, G8 and G17) and irrigation (100% and 50% of evapotranspiration). Results The results show the influence of irrigation and seed source on the antioxidant activity and total polyphenol content of Chia flower and stem. Inflorescences exhibit higher antioxidant activity suggesting their potential use as natural antioxidant. The mutants G3 and G8 at 50% irrigation contained the highest amounts of compounds with nutraceutical value especially within the flower. The mutant G17 showed lower antioxidant activity and polyphenol content compared to other seed sources but exhibited high omega 3 content in flowers but low in stems. This indicates that chia varieties should be chosen according to the objective of cultivation. Conclusion These finding, indicating a close relation of metabolite content with irrigation and seed source, may provide the basis for the use of Chia flower and stem for their nutraceutical value in the food, feed, and supplement industries. This article is protected by copyright. All rights reserved.
... 41 In addition, arbutin has been shown to have multiple e ects on cells, besides the inhibitory e ect on tyrosinase activity, such as antioxidant and anti-in ammatory e ects. 42,43 Furthermore, the stability of the lipophilic dispersions used for test formulations might have been more optimal for arbutin than for hydroquinone. This can be explained by the signi cant pigment lightening caused by arbutin. ...
Article
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Objective: Skin lightening agents are popular in southern Asia, but there is dearth of evidence on their effectiveness on Fitzpatrick IV/V skin types. This study was designed to assess the depigmenting efficacy of commercially available and specifically formulated ointments using the Mexameter® (MX 18). Methods: This single center prospective study was performed to test five commercially available preparations (Eldopaque®, Aziderm®, Garnier Dark Spot Corrector®, Ban a Tan Cream® and Neostrata Pigment Lightening Gel) on 28 healthy female volunteers in Phase 1, while five single active ingredients in lipophilic dispersion (hydroquinone 4%, ascorbyl palmitate 1%, resveratrol 1% arbutin 5% and azelaic acid 20%) were tested on a different group of 26 healthy female volunteers in Phase 2. The test agents were applied twice a day for five days per week and continued for six weeks in both study phases. Weekly Mexameter® measurements were obtained from test sites and negative controls. Results: Significant hypopigmentation when compared to untreated controls was observed with Aziderm cream (p<0.05, MWU) and the Neostrata Pigment Lightening Gel (p<0.05, MWU). All formulated preparations showed significant reduction in pigmentation; however, only the arbutin (5%) containing formulation revealed significant attenuation of pigmentation in comparison to the inactive control (p<0.05, MWU). Conclusion: All applications containing active ingredients showed significant skin lightening; however, only arbutin was able to demonstrate significant diminution of pigmentation when compared to the inactive control.
... Protective effects of arbutin have been reported in some conditions, such as diabetes [19], cancers [20], myocardial injury [21], and neurodegenerative diseases [22]. Although the exact mechanism by which arbutin induces protective effects in the mentioned diseases is not fully known, its anti-oxidant, anti-inflammatory, and antiapoptotic properties play an important role in such conditions [22][23][24][25]. Although the complete anti-inflammatory effects of arbutin remain to be elucidated, it has been shown to reduce the infiltration of inflammatory cells such as macrophages, mast cells, and neutrophils [26]. ...
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Purpose Efforts to produce radioprotective agents of high potentials are appropriate strategies for overcoming possible IR toxicity in organisms. The present research aims to evaluate the signaling pathways and mechanisms through which arbutin exerts radioprotective effects on organisms. Methods The databases of PubMed, Web of Sciences, Google Scholar, and Scopus were searched to find studies that reported radioprotective effects for arbutin. Besides, the data were searched within the time period from 2010 to 2020. Result Five research articles met our criteria, which were included in the analysis based on their relevance to the topic. The present systematic review provides conclusions about various mechanisms and pathways through which arbutin induces radioprotection. Conclusions Based on the relevant studies, various mechanisms can be proposed for inducing radioprotective effects by arbutin, including inhibition of oxidative stress, apoptosis, and inflammation.
... The classical structure-activity relationship theory directly correlates the number of oxidizable -OH groups in a molecule with its free radical scavenging efficacy. In previous studies, arbutin showed excellent 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activities because one molecule of arbutin can quench five radicals (Takebayashi et al., 2010). Recently reported data have reported that A2AR antagonists (e.g., SCH-58261, ZM-241385, KD-64, caffeine) protect against reactive oxygen species, nitric oxide synthase, cyclo-oxygenase, and microglia-mediated inflammation (Paterniti et al., 2011;Borea et al., 2018;Colella et al., 2018;Aires et al., 2019;Kotańska et al., 2020). ...
Article
An antagonistic communication exists between adenosinergic and dopaminergic signaling in the basal ganglia, which suggests that the suppression of adenosine A2A receptors-cyclic adenosine monophosphate pathway may be able to restore the disrupted dopamine transmission that results in motor symptoms in Parkinson’s disease (PD). Arbutin is a natural glycoside that possesses antioxidant, anti-inflammatory, and neuroprotective properties. The purpose of this study was to investigate whether arbutin could ameliorate the symptoms of PD and to examine the underlying mechanism. In this study, Swiss albino mouse models of PD were established by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 4 successive days, with the concurrent intraperitoneal administration of arbutin (50 and 100 mg/kg) for 7 days. The results showed that arbutin significantly reduced lipid peroxidation, total nitrite levels, and inflammation in the substantia nigra and striatum of PD mouse models. In addition, arbutin decreased the activity of endogenous antioxidants, reduced the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and γ-aminobutyric acid, and minimized neurodegeneration in the striatum. Arbutin also reduced the abnormal performance of PD mouse models in the open field test, bar test, pole test, and rotarod test. The therapeutic efficacy of arbutin was similar to that of madopar. The intraperitoneal injection of the A2AR agonist CGS21680 (0.5 mg/kg) attenuated the therapeutic effects of arbutin, whereas the intraperitoneal injection of forskolin (3 mg/kg) enhanced arbutin-mediated improvements. These findings suggest that arbutin can improve the performance of PD mouse models by inhibiting the function of the A2AR and enhancing the effects of cyclic adenosine monophosphate. This study was approved by the Institutional Animal Ethics Committee (1616/PO/Re/S/12/CPCSEA) on November 17, 2019 (approval No. IAEC/2019/010).
... [18,19] It possesses antioxidant properties and is therefore used as a skin-lightening agent. [20] In lipopolysaccharideinduced BV2 microglial cells, arbutin renders anti-inflammatory properties [21] and it also induces apoptosis in murine melanoma cells. [22] However, the anticancer potency of arbutin against glioma has not yet been elucidated. ...
Article
Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti‐inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute‐1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.
... In vitro Takebayashi et al. (2010) Prostate cancer Arbutin showed a prostate anticancer effect by increasing apoptosis and reducing expression of pro-inflammatory markers and ROS. ...
Article
Cosmetic dermatology preparations such as bleaching agents are ingredients with skin‐related biological activities for increasing and improving skin beauty. The possibility of controlling skin hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. Recently, cosmetics containing herbal and botanical ingredients have attracted many interests for consumers of cosmetic products because these preparations are found safer than other preparations with synthetic components. However, high‐quality trial studies in larger samples are needed to confirm safety and clinical efficacy of phytotherapeutic agents with high therapeutic index. Arbutin (p‐hydroxyphenyl‐β‐d‐glucopyranoside) is a bioactive hydrophilic polyphenol with two isomers including alpha‐arbutin (4‐hydroxyphenyl‐α‐glucopyranoside) and β‐arbutin (4‐hydroxyphenyl‐β‐glucopyranoside). It is used as a medicinal plant in phytopharmacy. Studies have shown that alpha‐arbutin is 10 times more effective than natural arbutin. A comparison of IC50 values showed that α‐arbutin (with concentration 2.0 mM) has a more potent inhibitory activity on human tyrosinase against natural arbutin (with higher concentration than 30 mM). A review of recent studies showed that arbutin could be beneficial in treatment of various diseases such as hyperpigmentation disorders, types of cancers, central nervous system disorders, osteoporosis, diabetes, etc. This study was designed to describe the therapeutic efficiencies of arbutin.
... Having in mind that decoction of this herbal mixture is characterized not only with a high content of polyphenols and flavonoids but also with the presence of even 10 biologically active compounds, i.e. isoquercetin, rutin, quercitrin, arbutin, hyperoside, astragalin, trifolin as well as gallic, quinic and caftaric acid [30], the results of this study are in agreement with previous studies where many naturally derived polyphenols, due to the high antioxidative activity [55][56][57][58] are well known for osteoprotective activities [59][60][61]. Namely, isoquercetin, the most abundant bioactive compound in the tested decoction [30], decreases the elevated level of oxidative stress in diabetic rats [62] and has anti-osteoporotic effect in ovariectomised rats [63]. ...
Article
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Bone loss leading to osteopenia and osteoporosis is a frequent secondary complication of diabetes. This study aimed to evaluate the value of a traditionally used 'anti-diabetic' polyherbal mixture as a possible remedy for the prevention of this complication. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate. The animals with blood glucose higher than 20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, animals were treated with two concentrations of the polyherbal mixture (10 and 20 g of dry plant material/ kg). Bone histopathology was evaluated using the H&E and Masson's trichrome staining. Alloxan-induced diabetes triggered bone histological changes characteristic for the development of osteopenia and osteoporosis and treatment with the polyherbal decoction restored these histopathological changes of the bones to the healthy animal level. At the same time, treatment with these tested doses has shown no adverse effects. These findings suggest that this mixture might be used as a remedy for the prevention of diabetic bone loss.
... (Table 4). Probably, these effects of arbutine in low doses may be related to strong antioxidant activity of Arbutine [37,34]. ...
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Arbutine is one of the active substances used as a skin whitening agent in cosmetic products. Possible effects of arbutine on hepatocelluler carcinoma (HepG2) cells and cisplatin toxication in HepG2 cells were investigated in this study. Cytotoxicity, genotoxicity, oxidative stress, inflammation, apoptosis and proliferation levels were determined in experimental groups established for the purpose above. It was determined that when low dose of α-arbutine (in LD 0 dose) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low dose of arbutine was used with cisplatin, it was observed that oxidative stress, inflammation, and genotoxicity levels increased as a result of cisplatin toxicity, but caspase 3 levels were not affected by this situation. As a result of high dose (in LD 50 dose) of α-arbutine administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In the presented study it was determined that as well as α-arbutine had an anticarcinogenic effect on HepG2 cells in high doses, it might be protective to reduce the side effects caused by low dose (LD 0 dose) of cisplatin treatment. In addition, it was concluded that α/β-arbutine-including cosmetic products were safe for cancer patients because α/β-arbutine had no effect on proliferation in HepG2 cells. In order to present the activity of arbutine isoforms more clearly it is recommended that studies should be conducted using healthy and different cell lines.
... In the polar fraction (Table 2), the GC-MS analysis determined d-Glucose (~18%) and Sucrose (~12%) as the most abundant substances, followed by Hydroquinone-βd-glucoside (arbutin) (~9%) and inositol (~8%). Arbutin-a principal constituent of T. diffusa -has been identified as having antioxidant compounds with gastroprotective activities (Taha et al., 2012;Takebayashi et al., 2010). ...
Article
Plant‐mediated nanoparticle synthesis is an eco‐friendly method designed to reduce toxicity. This research reports the effects of gold nanoparticle green synthesis on immune modulation for the first time, using aqueous extract from Turnera diffusa. First, the chemical composition showed that T. diffussa is abundant in compounds, such as oplopanone, γ‐eudesmol, hydroquinone‐β‐d‐glucoside (arbutin) and inositol. The synthesized gold nanoparticles (AuNPDam) were confirmed by ultraviolet visible (UV‐Vis) spectrophotometry; the micro‐graphical analysis confirmed the average size that was estimated about 24 nm, which were mostly spherical in shape. The Fourier transform infrared spectroscopy (FTIR) technique helped to confirm the functional groups of the synthesized AuNPDam. Its antioxidant capability was analysed using 2,2‐diphenyl‐1‐picrylhydarzyl (DPPH), superoxide radical scavenging and fluorescence recovery after photobleaching (FRAP) methods. These results indicated a worthy antioxidant activity. The synthesized AuNPDam showed strong antibacterial activity against Vibrio parahaemolyticus and Aeromonas hydrophila. Interestingly, AuNPDam were nontoxic to Longfin yellowtail head kidney leukocytes after 24 h. The phagocytosis activity, production of reactive oxygen species and nitric oxide were also enhanced in leukocytes treated with AuNPDam. Overall, the results suggested that AuNPDam is non‐cytotoxic, displays strong bactericidal activity and has therapeutic properties by enhancing the immune system.
... (Table 4). Probably, these effects of arbutine in low doses may be related to strong antioxidant activity of Arbutine [37,34]. ...
Preprint
Full-text available
Arbutine is one of the active substances used as a skin whitening agent in cosmetic products. Possible effects of arbutine on hepatocelluler carcinoma (HepG2) cells and cisplatin toxication in HepG2 cells were investigated in this study. Cytotoxicity, genotoxicity, oxidative stress, inflammation, apoptosis and proliferation levels were determined in experimental groups established for the purpose above. It was determined that when low dose of α-arbutine (in LD 0 dose) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low dose of arbutine was used with cisplatin, it was observed that oxidative stress, inflammation, and genotoxicity levels increased as a result of cisplatin toxicity, but caspase 3 levels were not affected by this situation. As a result of high dose (in LD 50 dose) of α-arbutine administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In the presented study it was determined that as well as α-arbutine had an anticarcinogenic effect on HepG2 cells in high doses, it might be protective to reduce the side effects caused by low dose (LD 0 dose) of cisplatin treatment. In addition, it was concluded that α/β-arbutine-including cosmetic products were safe for cancer patients because α/β-arbutine had no effect on proliferation in HepG2 cells. In order to present the activity of arbutine isoforms more clearly it is recommended that studies should be conducted using healthy and different cell lines.
Article
Chronic long-term glucocorticoid use causes osteoporosis partly by interrupting osteoblast homeostasis and exacerbating bone loss. Arbutin, a natural hydroquinone glycoside, has been reported to have biological activities related to the differentiation of osteoblasts and osteoclasts. However, the role and underlying mechanism of arbutin in glucocorticoid-induced osteoporosis are elusive. In this study, we demonstrated that arbutin administration ameliorated osteoporotic disorders in glucocorticoid dexamethasone (Dex)-induced mouse model, including attenuating the loss of bone mass and trabecular microstructure, promoting bone formation, suppressing bone resorption, and activating autophagy in bone tissues. Furthermore, Dex-stimulated mouse osteoblastic MC3T3-E1 cells were treated with arbutin. Arbutin treatment rescued Dex-induced repression of osteoblast differentiation and mineralization, the downregulation of osteogenic gene expression, reduced autophagic marker expression, and decreased autophagic puncta formation. The application of autophagy inhibitor 3-MA decreased autophagy, differentiation, and mineralization of MC3T3-E1 cells triggered by arbutin. Taken together, our findings suggest that arbutin treatment fends off glucocorticoid-induced osteoporosis, partly through promoting differentiation and mineralization of osteoblasts by autophagy activation.
Article
Arbutin is one of the active substances frequently used as a skin whitening agent in cosmetic products. Possible effects of arbutin on hepatocellular carcinoma (HepG2) cells and cisplatin toxicity in HepG2 cells were investigated in this study. Alpha and beta arbutin cytotoxicity levels in HepG2 cells were determined with the MTT method. Alpha arbutin cytotoxicity levels in HepG2 cells were lower than beta arbutin. Therefore, studies were continued with α-arbutin and genotoxicity (micronucleus and comet tests), inflammation (TNF-α, IL-6, and TGF-β), oxidative stress (MDA, GSH, NO, TAS, TOS, and OSI), apoptosis (caspase 3 and p53) and proliferation (Bcl-2) levels were determined in experimental groups. It was determined that when a low concentration of α-arbutin (in LD0 concentration; 0.022 mM) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low concentration of arbutin was used with cisplatin (in 11.06 µg/mL concentration ), it was observed that oxidative stress, inflammation, and genotoxicity levels statistically decreased as a result of cisplatin toxicity. However caspase 3 levels were not affected by this situation. As a result of high concentration (in LD50 concentration; 57.471 mM) of α-arbutin administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In addition, it was concluded that α/β-arbutin-including cosmetic products were safe for hepatocarcinoma patients because α/β-arbutin did not affect on proliferation in HepG2 cells.
Article
To examine the biological activity of polysaccharide extracted from cultured mycelia of Schizophyllum commune, we determined anti-complementary activity and nitric oxide production as a measure of immunological activity, anti-lipidperoxidation and hydroxy radical scavenging activity as a measure of antioxidative activity, tyrosinase inhibitory activity, anti-microbial activity, and transdermal flux of polysaccharide extracted from cultured mycelia of S. commune. Polysaccharide extracted from S. commune activated the complementary system and produced nitric oxide in RAW 264.7 macrophages. Antioxidant activities as malondialdehyde values were 49.5±0.7, 39.7±1.7, 39.2±1.2, and 2.6±0.5 nM/mL for control, extracellular polysaccharide extracted from S. commune (SC-EP), ultrafiltrated polysaccharide extracted from S. commune (SC-UP), and butylated hydroxytoluene, respectively. Hydroxy radical scavenging activity (IC50) of SC-UP and mannitol were 3.32 and 1.66 mg/mL, respectively. Tyrosinase inhibitory activities of SC-UP, arbutin, and kojic acid were 19.9%, 31.8%, and 99.0%, respectively. Anti-microbial activities of SC-UP appeared to be low, and transdermal fluxes of SC-UP were 0.47%, 0.73%, and 1.20% after 3, 6, and 9 hr, respectively. These findings suggest that polysaccharide extracted from S. commune has potential immunological and antioxidant activities. © 2014, Korean Society of Food Science and Nutrition. All rights reserved.
Article
Although numerous biologically active molecules exist as glycosides in nature, information on the activity, stability and solubility of glycosylated antioxidants is rather limited to date. In this work, a wide variety of antioxidants were glycosylated using different phosphorylase enzymes. The resulting antioxidant library, containing α/β-glucosides, different regio-isomers, cellobiosides and cellotriosides was then characterized. Glycosylation was found to significantly increase the solubility and stability of all evaluated compounds. Despite decreased radical scavenging abilities, most glycosides were identified to be potent antioxidants, outperforming the commonly used 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT). Moreover, the point of attachment, the anomeric configuration, and the glycosidic chain length were found to influence the properties of these phenolic glycosides.
Article
Background: Neutrophils are present in high numbers in areas of inflammation, where they constitute an important source of reactive oxygen metabolites. The massive production of antimicrobial and tumoricidal reactive oxygen metabolites in an inflammatory environment is called "oxidative burst" and plays an important role as the first line of defence against environmental pathogens. A wide array of phenolic substances, particularly those present in edible and medicinal plants, have been reported to possess substantial antioxidative, anticarcinogenic and antimutagenic activities by modulating important cellular signalling processes. Essential: In this study we investigated the effect of four commercially available/and or synthetized natural polyphenols arbutin, curcumin, pinosylvin and pterostilbene on the generation of reactive oxygen species in stimulated human blood and isolated neutrophils measured by chemiluminescence. Methods: For isolated neutrophils differential centrifugation was applied. The oxidative burst in stimulated blood and isolated neutrophils was measured by luminol/isoluminol enhanced chemiluminiscence in samples stimulated by phorbolmyristate acetate. Data were calculated from the area under the chemiluminescence curves measured in a luminometer Immunotec LM-01T over 5 min. Results: Oxidative burst in stimulated whole human blood was decreased by the compounds tested in the rank order of potency: curcumin > pterostilbene > arbutin > pinosylvin. Extracellularly pinosylvin was the least active; a significant identical dose-dependent inhibitory effect was recorded for the other compounds tested. The rank order of potency for intracellular inhibition of oxidative burst was: curcumin > pinosylvin > pterostilbene. Arbutin was without any effect. Conclusion: The supportive effect of the polyphenols tested might be therapeutically beneficial for treatment of inflammation, ischaemia-reperfusion, neoplastic growth and other pathological stages.
Article
This study was carried out to investigate the total polyphenols, antioxidant activities, and melanin synthesis inhibition of several pear cultivars (Pyruspyrifolia). The total polypenolic content of five pear cultivars was high in the unripe developmental stage. Total polyphenolic content of the Chuwhangbae cultivar extract was higher than that of other pear cultivars regardless of the developmental stage. However, the total flavonoid content did not differ between cultivars or developmental stages. The phenolic compound, arbutin has an inhibitory effect on melanogenesis. Arbutin levels in pear cultivars declined as the fruit matured. The free radical scavenging activity of the extract also decreased as the fruit ripened. In B16F10 mouse melanoma cells, most of the cultivar extracts inhibited melanin synthesis by about 50% at a 100 μg·mL-1 concentration, except in the Gamcheonbae extract until 90 days after full bloom. We have confirmed that the extract of pear cultivars have antioxidant activity and skin-whitening effects.
Article
Turnera ulmifolia L. (Fam. – Turneraceae) is a perennial shrub and is used in the treatment of anemia, bronchitis, cough, diabetes, dysmenorrhea, hemorrhage, toothache, metrorrhagia, lumbago, dyspepsia, dysentery, fever, skin infections, pain, pulmonary and respiratory complaints, health problems of women, chest ailments, biliousness, indigestion, and rheumatism. Its leaves are used as a tonic and curing ofmasculine insufficiency and perimenopausal and menopausal complaints. Turnera aphrodisiaca is considered as an aphrodisiac, stimulant, nerve tonic, and laxative agent and is also used in kidney, menstrual, and pregnancy problems; as well as decoction for patrrturition in California. The optimal conditions were determined for callus induction in T. diffusa. The Murashige and Skoog and B5 media were tested with various combinations of 2,4‐dichlorophenoxyacetic acid and 6‐benzyladenine for induction of callus.
Article
Introduction: Plants and algae have played a central role in the treatment of skin conditions in both traditional First Nations healing and in modern dermatology. The objective of this study was to examine the evidence supporting the dermatological use of seaweed, witch hazel, bearberry, and mayapple. Methods: Four plants and algae used in traditional First Nations treatments of skin disease were selected based on expert recommendations. Several databases were searched to identify relevant citations without language restrictions. Results: Seaweed has potential clinical use in the treatment of acne and wrinkles and may be incorporated into biofunctional textiles. Witch hazel is an effective and well-tolerated treatment of inflammation and diaper dermatitis. Bearberry leaves contain arbutin, a skin-lightening agent that is an alternative for the treatment of hyperpigmentation. Mayapple contains podophyllotoxin, a treatment for condyloma accuminata, molluscum contagiosum, and recalcitrant palmoplantar warts. Discussion: Common plants and algae are replete with bioactive agents that may have beneficial effects on the skin. Further research will open the door to new and innovative products in the future. Limitations of this study include that the scope of our study is limited to 4 plants and algae, a small sample of the breadth of plants used by First Nations for dermatological treatments.
Article
Arbutin, a glucoside of hydroquinone, has shown strong ABTS radical cation-scavenging activity, especially in reaction stoichiometry. In this study, we investigated the reaction mechanism of arbutin against ABTS radical cation that caused high stoichiometry of arbutin in an ABTS radical cation-scavenging assay. HPLC analysis of the reaction mixture of arbutin and ABTS radical cation indicated the existence of two reaction products. The two reaction products were purified and identified to be a covalent adduct of arbutin with an ABTS degradation fragment and 3-ethyl-6-sulfonate benzothiazolone. A time-course study of the radical-scavenging reactions of arbutin and the two reaction products suggested that one molecule of arbutin scavenges three ABTS radical cation molecules to generate an arbutin–ABTS fragment adduct as a final reaction product. Our results suggest that one molecule of arbutin reduced two ABTS radical cation molecules to ABTS and then cleaved the third ABTS radical cation molecule to generate two products, an arbutin–ABTS fragment adduct and 3-ethyl-6-sulfonate benzothiazolone.
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Three germacranolides, as well as five flavonoids, natural steroid and simple phenolic compounds, were isolated from the inflorescence of Stizolophus balsamita growing in Iran. The paper presents active compounds found for the first time in the inflorescence of this species. The flavonoids, simple phenolic compounds and natural steroids have been isolated for the first time in the genus Stizolophus. The MTT assay was employed to study in vitro cytotoxic effects of the taxifolin against human fibroblasts. We also evaluate the possible biological properties/cosmetic effects of Stizolophus balsamita extract and taxifolin on the human skin. Sixty healthy Caucasian adult females with no dermatological diseases were investigated. We evaluate the effects of S. balsamita extract and taxifolin on skin hydration and transepidermal water loss (TEWL). It was revealed that S. balsamita extract might decrease TEWL level and fixed the barrier function of the epidermis. The presence of bioactive phytochemical constituents in S. balsamita inflorescences makes them a valuable and safe source for creating new cosmetics and medicines.
Article
2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2G) exhibits biological activities after enzymatic hydrolysis to ascorbic acid (AA) by α-glucosidase. We have found that AA-2G per se exerted radical-scavenging activity toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH radical). The radical-scavenging property of AA-2G was greatly different from that of AA; that is, the reaction rate with DPPH radical of AA-2G was far slower than that of AA, but the long-lasting radical-scavenging ability per one molecule of AA-2G was superior to that of AA. We purified key intermediates for the characteristic radical-scavenging reaction of AA-2G and carried out time-course studies of the radical-scavenging reactions of the intermediates, AA-2G and AA to determine both the reaction rate and stoichiometry of AA-2G with DPPH radical. One mole of AA-2G quenched 2.7 moles of DPPH radical over a period of 120 min, while one mole of AA quenched 1.9 moles of the radical. The high reaction stoichiometry of AA-2G against DPPH radical was associated with adduct formation of AA-2G with DPPH radical. The radical-scavenging reaction mechanism of AA-2G consists of the following three steps: (1) At an early stage of the reaction, AA-2G scavenged DPPH radical to generate AA-2G radical, (2) AA-2G radical immediately reacted with an additional DPPH radical to give two types of AA-2G–DPPH adducts and (3) AA-2G–DPPH adducts slowly quenched the other DPPH radical to generate several reaction products. Our results suggest the practical value of AA-2G, even before being converted into AA, as a beneficial antioxidant in food and cosmetic applications.
Article
Arbutin is a simple phenolic glucoside biosynthesised in many plant families. Some of the everyday foods that contain arbutin are species of the genus Origanum, peaches, cereal products, coffee and tea and Arctostaphyllos uva ursi L. leaves. Arbutin possesses various beneficial effects in the organism, and was confirmed effective in the treatment of urinary tract infections as well as in preventing skin hyperpigmentation. It shows antioxidant and anti-inflammatory properties, and antitumor activity. The aim of this study was to explore potential radioprotective properties of arbutin in concentrations of 11.4 μg/mL, 57 μg/mL, 200 μg/mL and 400 μg/mL administered as a pre-treatment for one hour before exposing human leukocytes to ionising radiation at a therapeutic dose of 2 Gy. The alkaline comet assay was used to establish the levels of primary DNA damage, and cytokinesis-block micronucleus (CBMN) cytome assay to determine the level of cytogenetic damage. None of the tested concentrations of single arbutin showed genotoxic and cytotoxic effects. Even at the lowest tested concentration, 11.4 μg/mL, arbutin demonstrated remarkable potential for radioprotection in vitro, observed both at the level of primary DNA damage, and using CBMN cytome assay. The best dose reduction compared with amifostine was observed after pre-treatment with the highest concentration of arbutin, corresponding to 400 μg/mL. Promising results obtained on the leukocyte model speak in favour of extending similar experiments on other cell and animal models.
Article
Alcoholic liver disease (ALD) is a pervasive ailment due to the excessive consumption of alcohol and there is no operative drug for its treatment. The current exploration was intended to examine the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats via the modulation of the Nrf-2/HO-1 signaling cascade. Wistar rats were challenged with the 3 g/kg/day (40% v/v) of ethanol for 4 weeks to provoke the ALD and concomitantly supplemented with 40 mg/kg of arbutin. The liver function markers enzymes, inflammatory cytokines, and oxidative stress markers levels were scrutinized by using the respective assay kits. The mRNA expression of Nrf-2/HO-1 signaling proteins was studied by reverse-transcription polymerase chain reaction. The histological alterations of liver tissues were examined. HepG2 cells were used for the in vitro studies. The levels of oxidative stress markers and liver marker enzymes were examined by using kits. Reactive oxygen species (ROS) and apoptotic cell death was detected by using fluorescent staining. There were no major differences in the body weight and liver weight of experimental animals. Arbutin treatment appreciably reduced the liver marker enzymes, upregulated superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and the hydroxyl scavenging ability, and diminished the tumor necrosis factor-α and interleukin-6 levels in the serum of ethanol provoked animals. Arbutin triggered Nrf-2/HO-1 signaling cascade liver tissues of ethanol-provoked animals. Histological findings proved the preventing effects of arbutin. Arbutin did not demonstrate toxicity to the HepG2 cells. It reduced the aspartate aminotransferase and alanine aminotransferase, ROS, apoptotic cell death, lipid peroxidation and improved the antioxidants' levels in the ethanol-challenged HepG2 cells. In conclusion, our findings unveiled the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats. It could be a promising agent to treat alcoholic liver disease in the future.
Article
The main goal of this study was to evaluate the effects of arbutin (AR) on lipopolysaccharide (LPS)-induced lung injury. A lung injury rat model was established by intravenous LPS administration. We found that levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in both serum and lung tissue were significant increased after LPS challenge. In addition, pathological conditions were examined in rat lungs, and it was demonstrated that AR-pretreatment reduced LPS-induced malondialdehyde (MDA) levels and increased LPS-induced superoxide dismutase (SOD) activity. Moreover, the expression of sirtuin1 (SIRT1), nuclear erythroid factor 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) as well as the phosphorylation of NF-κBp65 and IκBα were increased with LPS-induced lung injury, and were significantly restored by AR treatment. Together, our results indicated that SIRT1 is a potential therapeutic target in LPS-induced lung injury, and that AR may be a novel therapeutic in patients with acute lung injury.
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Arbutin, a glycoside, is derived from the leaves of several plants, including wheat, pear, and bearberry plants and has a significant role in the treatment of melanoma, cystitis, and cough. Here, we aimed to modify Yarrowia lipolytica to produce arbutin. To construct the arbutin synthetic pathway in Y. lipolytica, three genes (chorismate pyruvate-lyase (UbiC), 4-hydroxybenzoate 1-hydroxylase (MNX1) and hydroquinone glucosyltransferase (AS)) were codon-optimized and heterologously expressed. To maximize arbutin production, seven arbutin-biosynthesis molecular targets were overexpressed, and we found that the individual strengthening of DHS1 and DHS2 led to an 8.9 and a 7.8-fold improvement in arbutin yield, respectively. Through optimization, a maximum arbutin titer of 8.6 ± 0.7 g/L was achieved using the finally engineered strain, po1f-At09. Overall, this is the first report of heterologous arbutin synthesis in Y. lipolytica at a high titer. Furthermore, this work opens a possibility for the overproduction of shikimate pathway derivatives in Y. lipolytica.
Book
Exposure to solar radiation, other environmental insults, and inflammation all produce free radicals in skin. The damage caused by free radicals includes many pathological diseases, including skin cancer. That is why for more than two decades now, researchers diligently continue to explore the use of antioxidants to mitigate the damage caused by free radicals. It is now a well-known fact that treatment of skin with antioxidants is a clinically efficacious way to combat the perils of free radical-induced skin damage. Early research exploited the benefits of common antioxidants, such as vitamins E and C, to prevent photoaging, photoimmunosuppression, and photocarcinogenesis of skin. Accordingly, most skin preparations launched in the marketplace during that period contained these and other small molecule antioxidants, such as butylated hydroxytoluene or butylated hydroxyanisole. More recently, research on the protective benefits of botanical extracts containing powerful phytoantioxidants shed light on the advantages of this class of compounds in combating free radical damage in skin. As a result, phytoantioxidants are now much more prevalent in today’s modern skin care preparations. One need only look at the extensive list of botanicals on skin cream ingredient labels currently on store shelves to see that this is true. The amount of scientific information available about antioxidants can be, to put it mildly, overwhelming. Book chapters appear here and there and new articles are published regularly in an everincreasing number of journals. So, it is easy to find one’s self adrift in a large pool of information not knowing how to stay afloat or in which direction to swim. Antioxidants and the Skin attempts to bring all of this information together in one logically organized and easy-to-digest text. It reaches out to investigators of all disciplines to provide a comprehensive treatise on the subject. The book is suitable for a wide range of readers. Whether it be someone just starting their journey in the realm of antioxidants, or a more seasoned antioxidant veteran who has need of a valuable reference tool. Moreover, this text features fundamental aspects of skin biochemistry, an introduction to free radical species and how they damage biological systems, a thorough overview of the skin’s endogenous antioxidant network, and sources of free radical damage including solar irradiation. In addition, a chapter is included that presents concepts of lipid peroxidation and how it affects both the skin (its lipids) and formulations. It provides key information about lipid per oxidation in vivo, in vitro, and in formulation (colloidal) systems. This book also includes an overview of the essential technique for measuring free radicals, electron spin resonance, as well as discussion of the efficacy of antioxidant treatments and a chapter that cites key antioxidants used in formulations, their physical/chemical properties, and references analytical and efficacy studies that substantiate their performance and effectiveness. It is my hope that many researchers, formulators, clinicians, and academic instructors will find the contents of this book beneficial in their investigations with antioxidants and the skin. Roger L. McMullen
Article
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The oxidative hemolysis of rabbit erythrocytes induced by free radicals and its inhibition by chain-breaking antioxidants have been studied. The free radicals were generated from either a water-soluble or a lipid-soluble azo compound which, upon its thermal decomposition, gave carbon radicals that reacted with oxygen immediately to give peroxyl radicals. The radicals generated in the aqueous phase from a water-soluble azo compound induced hemolysis in air, but little hemolysis was observed in the absence of oxygen. Water-soluble chain-breaking antioxidants, such as ascorbic acid, uric acid, and water-soluble chromanol, suppressed the hemolysis dose dependently. Vitamin E in the erythrocyte membranes was also effective in suppressing the hemolysis. 2,2,5,7,8-Pentamethyl-6-chromanol, a vitamin E analogue without phytyl side chain, incorporated into dimyristoylphosphatidylcholine liposomes, suppressed the above hemolysis, but alpha-tocopherol did not suppress the hemolysis. Soybean phosphatidylcholine liposomes also induced hemolysis, and a lipid-soluble azo initiator incorporated into the soybean phosphatidylcholine liposomes accelerated the hemolysis. The chain-breaking antioxidants incorporated into the liposomes were also effective in suppressing this hemolysis.
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Methods available for the measurement of antioxidant capacity are reviewed, presenting the general chemistry underlying the assays, the types of molecules detected, and the most important advantages and shortcomings of each method. This overview provides a basis and rationale for developing standardized antioxidant capacity methods for the food, nutraceutical, and dietary supplement industries. From evaluation of data presented at the First International Congress on Antioxidant Methods in 2004 and in the literature, as well as consideration of potential end uses of antioxidants, it is proposed that procedures and applications for three assays be considered for standardization: the oxygen radical absorbance capacity (ORAC) assay, the Folin-Ciocalteu method, and possibly the Trolox equivalent antioxidant capacity (TEAC) assay. ORAC represent a hydrogen atom transfer (HAT) reaction mechanism, which is most relevant to human biology. The Folin-Ciocalteu method is an electron transfer (ET) based assay and gives reducing capacity, which has normally been expressed as phenolic contents. The TEAC assay represents a second ET-based method. Other assays may need to be considered in the future as more is learned about some of the other radical sources and their importance to human biology.
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Both physicians and dermatology patients are searching for long-term topical skin care solutions (both cosmetic and cosmeceutical) to address problems presented by skin hyperpigmentation. Specifically, some women often express a desire to "lighten" skin tone by achieving improved visible tone, reduction in yellowness (or sallow tone), and reduction in the appearance of hyperpigmented spots ("age" or "sun" spots). Traditional depigmenting agents, such as hydroquinone, corticosteroids, and kojic acid, although highly effective, can raise several safety concerns (for example, ochronosis, atrophy, carcinogenesis, and other local or systemic side effects) with long-term exposure. An understanding of the benefits of natural and botanical extracts provides opportunities to develop new products to address pigmentation problems. Active compounds isolated from plants, such as arbutin, aloesin, gentisic acid, flavonoids, hesperidin, licorice, niacinamide, yeast derivatives, and polyphenols, inhibit melanogenesis without melanocytotoxicity by different mechanisms. This review presents an overview of trends in the application of plant extracts as topical treatments for hyperpigmentation disorders. It highlights some of the most relevant natural extracts, providing in vitro screening results and relevant available clinical study trial findings supporting their efficacy.
Article
Radical scavenging of four tea catechins, (-)-epicatechin (EC), (-)- epigallocatechin (EGC), (-)-epicatechin gallate (ECg) and (-)- eppigallocatechin gallate (EGCg), and the model compounds of their partial structure was examined against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical using stopped-flow and spectrophotometric methods. The number of DPPH radicals scavenged by a polyphenol molecule was larger than that of phenolic hydroxyl groups, suggesting that hydrogens which bond directly to the aromatic ring can also participate in radical scavenging. A model for the scavenging reaction was proposed in which the reaction proceeded with successive dehydrogenation from a polyphenol molecule. Analysis of the second order reaction rate constants and the activation parameters between DPPH and polyphenol at the early stage of the reaction showed that the values depended on the number of phenolic hydroxyl groups and their mutual position. Contribution of the A ring of catechins to the rate constants was estimated to be far smaller than that from the B ring. In the EGCg molecule, the B ring and the gallate group were not independent, but acted as a single group for DPPH radical scavenging.
Article
Fifty-one tannins and forty-one flavonoids isolated from Oriental medicinal herbs were evaluated for their antioxidant ability with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-generating system. The results showed that tannins and certain flavonoids are potential free-radical scavengers, and that their activity against the DPPH radical is closely associated with their chemical structure. A comparison of the two classes of compounds showed that tannins have more potential than flavonoids because almost all the tannins demonstrated significant scavenging action within a low concentration range, whereas the activity of flavonoids varied distinctively among the different compounds. An increase of galloyl groups, molecular weight, and ortho-hydroxyl structure enhanced the activity of tannins, whereas the number and position of hydroxyl groups were important features for the scavenging of free radicals by flavonoids. Moreover, it appeared that when the free hydroxyl group was methoxylated or glycosylated, the inhibitory activity was obviously decreased or even abolished.
Article
The aim of this study was to characterize the antioxidant activity of three ascorbic acid (AA) derivatives O-substituted at the C-2 position of AA: ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S). The radical-scavenging activities of these AA derivatives and some common low molecular-weight antioxidants such as uric acid or glutathione against 1,1-diphenyl-picrylhydrazyl (DPPH) radical, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS⁺), or galvinoxyl radical were kinetically and stoichiometrically evaluated under pH-controlled conditions. Those AA derivatives slowly and continuously reacted with DPPH radical and ABTS⁺, but not with galvinoxyl radical. They effectively reacted with DPPH radical under acidic conditions and with ABTS⁺ under neutral conditions. In contrast, AA immediately quenched all species of radicals tested at all pH values investigated. The reactivity of Trolox, a water-soluble vitamin E analogue, was comparable to that of AA in terms of kinetics and stoichiometrics. Uric acid and glutathione exhibited long-lasting radical-scavenging activity against these radicals under certain pH conditions. The radical-scavenging profiles of AA derivatives were closer to those of uric acid and glutathione rather than to that of AA. The number of radicals scavenged by one molecule of AA derivatives, uric acid, or glutathione was equal to or greater than that by AA or Trolox under the appropriate conditions. These data suggest the potential usage of AA derivatives as radical scavengers.
Article
The 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS·+) decolorization assay was applied to evaluate the stoichiometric radical scavenging activity of ascorbic acid (AA) and two AA derivatives, 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) and 2-O-α-D-glucopyranosyl-6-O-octanoyl-L-ascorbic acid (6-Octa-AA-2G). AA rapidly reacted with ABTS·+, and the reaction was completed within 10 min. In contrast, AA-2G and 6-Octa-AA-2G continuously reacted with ABTS·+, and the reaction was not completed after 2 h. The radical scavenging activity of AA-2G and 6-Octa-AA-2G in aqueous solutions at pH 4.0 and above was higher than that at pH 3.0, whereas AA showed no difference in the pH range 3 to 6. The amounts of ABTS·+ scavenged by one molecule of AA, AA-2G and 6-Octa-AA-2G after 2 h of reaction at pH 6.0 were approximately 2.0, 3.4 or 3.9 molecules, respectively. This study demonstrates that the quantity of ABTS·+ quenched by AA-2G and 6-Octa-AA-2G is superior to that of AA in a long-term reaction.
Article
METHODS for measuring antioxidants and appraising antioxidant activity appear to be of two general types. If the chemical nature of the antioxidant is known, one may strive for a test specific for the compound or group of interest; for example, the nitroprusside test for sulphydryl groups. Alternatively one may observe the inhibition of some natural oxidative process such as the β-oxidation of fats, as a function of the added antioxidant.
Article
The antioxidant capacity of a series of structurally related flavonoids is quantified by the amount of ABTS [2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonate)] radical anions (ABTS–) that is able to react with the flavonoid and expressed as the Trolox equivalent antioxidant capacity (TEAC). To evaluate the predictive value of the TEAC, the antioxidant activity of this series of flavonoids was also assessed in other in vitro assays, measuring the effect on hydroxyl scavenging, lipid peroxidation and doxorubicin-induced toxicity as typical scavenging or damage assays. The flavonoids tested were mono HER, di HER, tri HER, tetra HER and tri HEQ, differing in the number of aromatic hydroxyl groups. It was found that these compounds showed both a fast and slow scavenging effect in the TEAC assay and therefore the TEAC at 10 s (‘fast’ TEAC) and 6 min (‘total’ TEAC) was determined. Both this ‘total’ and ‘fast’ TEAC are negatively correlated with hydroxyl radical scavenging. The ‘total’ TEAC showed a better correlation than the ‘fast’ TEAC with the inhibition of lipid peroxidation and the protection against doxorubicin-induced toxicity. This indicates that beside the fast reaction of scavengers with the ABTS radical, also the slow reaction should be taken into consideration. It is concluded that the antioxidant capacity, assessed with the modified TEAC assay, can be useful to predict the in vivo antioxidant effect in a series of structurally related compounds.
Article
The antiradical activities of various antioxidants were determined using the free radical, 2,2-Diphenyl-1-picrylhydrazyl (DPPH*). In its radical form. DPPH* has an absorption band at 515 nm which dissappears upon reduction by an antiradical compound. Twenty compounds were reacted with the DPPH* and shown to follow one of three possible reaction kinetic types. Ascorbic acid, isoascorbic acid and isoeugenol reacted quickly with the DPPH* reaching a steady state immediately. Rosmarinic acid and δ-tocopherol reacted a little slower and reached a steady state within 30 min. The remaining compounds reacted more progressively with the DPPH* reaching a steady state from 1 to 6 h. Caffeic acid, gentisic acid and gallic acid showed the highest antiradical activities with a stoichiometry of 4 to 6 reduced DPPH* molecules per molecule of antioxidant. Vanillin, phenol, γ-resorcylic acid and vanillic acid were found to be poor antiradical compounds. The stoichiometry for the other 13 phenolic compounds varied from one to three reduced DPPH* molecules per molecule of antioxidant. Possible mechanisms are proposed to explain the experimental results.
Article
The antioxidant capacity of a group of fruits obtained in the Singapore markets was investigated. A total of 27 fruit pulps were tested for their general antioxidant capacity based on their ability to scavenge 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radical. The contribution of l-ascorbic acid (AA) to the total antioxidant activity of fruits was investigated by using RP-HPLC. The antioxidant capacity of the fruit pulp was measured by monitoring the change of absorbance of the free radical solution at 414 nm in the test reaction mixture following addition of the fruit extract, as compared with AA. The results were expressed as mg of AA equivalents per 100 g, i.e. the quantity of AA required to produce the same scavenging activity as the extract in 100 g of sample (l-ascorbic acid equivalent antioxidant capacity, AEAC). Total antioxidant capacities of AA acid, trolox, hydroquinone, pyrogallol and several fruits were also evaluated based on its ability to scavenge the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical. Results obtained were compared with those of ABTS assay. Every mol of AA, trolox or hydroquinone, was found to reduce about 2 mol of ABTS+ or DPPH. However, 4 mol of DPPH or 7 mol of ABTS+ were scavenged by every mol of pyrogallol. A good correlation of AEAC was observed between the two methods. Both methods have been recommended to be useful tools to evaluate antioxidant capacities of fruits. According to the AEAC value of binary extract solution of fruits in the ABTS model, ciku shows the highest antioxidant capacity, followed by strawberry, plum, star fruit, guava, seedless grape, salak, mangosteen, avocado, orange, solo papaya, mango, kiwi fruit, cempedak, pomelo, lemon, pineapple, apple, foot long papaya, rambutan, rambutan king, banana, coconut pulp, tomato, rockmelon, honeydew, watermelon and coconut water. The AA contribution to AEAC of fruits varied greatly among species, from 0.06% in ciku to 70.2% in rambutan.
Article
There are many in vitro methods for evaluating antioxidant activity. In this chapter, we describe an operationally simple cell-based assay, oxidative hemolysis inhibition assay (OxHLIA). OxHLIA is based on inhibition of free radical-induced membrane damage in erythrocytes by antioxidants. The advantage of this method is that it uses peroxyl radicals as pro-oxidants and erythrocytes as oxidizable targets so that the results obtained reflect biologically relevant radical-scavenging activity and microlocalization of antioxidants. We also present here a comparison of OxHLIA with other common methods (DPPH, ABTS(*+), and ORAC assays).
Article
Arbutin, the beta-D-glucopyranoside of hydroquinone, is a skin whitening cosmetic ingredient. Compared with arbutin, hydroquinone is a more potent skin lightening agent, but shows cytotoxicity, nephrotoxicity, and genotoxicity. To evaluate whether skin microflora can hydrolyze arbutin to hydroquinone, we measured the hydrolytic activity of the main skin microflora: Staphylococcus epidermidis and Staphylococcus aureus. All strains hydrolyzed arbutin, with activities of 0.16-4.51 nmol/min/mg. The hydrolyzed hydroquinone showed more potent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and tyrosinase inhibition than arbutin. These findings suggest that normal skin microflora may increase the skin lightening effect of arbutin due to the antioxidant action of hydroquinone.
Article
The accumulation of 2.2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical catalyzed by peroxidase can be inhibited by the presence of L-ascorbic acid in the reaction medium, this inhibition delaying the accumulation of the ABTS radical and giving rise to a lag time. A kinetic approach to explain this lag time is presented, which also makes it possible to determine the amount of L-ascorbic acid in the reaction medium. The stoichiometry of the system was determined as 1 mol of L-ascorbic reducing 2 mol of ABTS radicals. L-Ascorbic acid is not the only compound to have this ability, since other antioxidant compounds also react with the ABTS radical. We studied the ABTS/H2O2/horseradish peroxidase system in the presence of L-ascorbic acid and other antioxidant compounds. The influence of such factors as pH, enzyme concentration, and L-ascorbic acid concentration was studied. A good correlation between the lag time and the L-ascorbic acid present in the medium was observed, and under optimal conditions, the method could determine as little as 0.65 nmol of L-ascorbic acid. Based on our findings, we propose a method to measure the total antioxidant activity of different compounds related to L-ascorbic acid and apply this method to determining the total antioxidant activity present in fruit juices.
Article
The recent explosion of interest in the bioactivity of the flavonoids of higher plants is due, at least in part, to the potential health benefits of these polyphenolic components of major dietary constituents. This review article discusses the biological properties of the flavonoids and focuses on the relationship between their antioxidant activity, as hydrogen donating free radical scavengers, and their chemical structures. This culminates in a proposed hierarchy of antioxidant activity in the aqueous phase. The cumulative findings concerning structure-antioxidant activity relationships in the lipophilic phase derive from studies on fatty acids, liposomes, and low-density lipoproteins; the factors underlying the influence of the different classes of polyphenols in enhancing their resistance to oxidation are discussed and support the contention that the partition coefficients of the flavonoids as well as their rates of reaction with the relevant radicals define the antioxidant activities in the lipophilic phase.
Article
Twenty-five compounds (trimetazidine derivatives and other compounds, mostly having a free phenolic group) were examined for their radical scavenging and antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl) as a measure of radical scavenging capacity was assessed by two parameters, namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z, a kinetic parameter proposed here and derived from initial second-order rate constants and antioxidant/DPPH ratios. Antioxidant activities were determined by the inhibition of lipid peroxidation and albumin oxidation. The most active compounds were derivatives having a trolox or hydroquinone moiety. Physicochemical and structural properties were determined by molecular modeling as lipophilicity (virtual log P calculations) and H-Surf (solvent-accessible surface of hydroxyl hydrogen) and by quantum mechanical calculations (deltaH(ox) = oxidation enthalpy; deltaH(abs) = enthalpy of hydrogen abstraction). QSAR models were derived to identify molecular mechanisms responsible for the reactivity toward the DPPH radical and for the inhibition of lipid peroxidation. A useful prediction of antioxidant capacity could be achieved from calculated molecular properties and the kinetic parameter developed here.
Article
To discover safe and effective topical skin-lightening agents, we have evaluated alkyl esters of the natural product gentisic acid (GA), which is related to our lead compound methyl gentisate (MG), and four putative tyrosinase inhibitors, utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the ability to inhibit melanogenesis in cells (IC50 < 100 microg/mL) without cytotoxicity, preferably due to tyrosinase inhibition. Of the six esters synthesized, the smaller esters (e.g. methyl and ethyl) were more effective enzyme inhibitors (IC50 approximately 11 and 20 microg/mL, respectively). For comparison, hydroquinone (HQ), a commercial skin "bleaching" agent, was a less effective enzyme inhibitor (IC50 approximately 72 microg/mL), and was highly cytotoxic to melanocytes in vitro at concentrations substantially lower than the IC50 for enzymatic inhibition. Kojic acid was a potent inhibitor of the mammalian enzyme (IC50 approximately 6 microg/mL), but did not reduce pigmentation in cells. Both arbutin and magnesium ascorbyl phosphate were ineffective in the cell-free and cell-based assays. MG at 100 microg/mL exhibited a minimal inhibitory effect on DHICA oxidase (TRP 1) and no effect on DOPAchrome tautomerase (TRP-2), suggesting that MG inhibits melanogenesis primarily via tyrosinase inhibition. MG and GA were non-mutagenic at the hprt locus in V79 Chinese hamster cells, whereas HQ was highly mutagenic and cytotoxic. The properties of MG in vitro, including (1) pigmentation inhibition in melanocytes, (2) tyrosinase inhibition and selectivity, (3) reduced cytotoxicity relative to HQ, and (4) lack of mutagenic potential in mammalian cells, establish MG as a superior candidate skin-lightening agent.
Article
Skin is a highly metabolic tissue which possesses the largest surface area in the body and serves as the protective layer for internal organs [1]. Skin is also a major candidate and target of oxidative stress. It is designed to give both physical and biochemical protection, and is equipped with a large number of defense mechanisms. The skin tissue is exposed to a variety of damaging species which originate in the outer environment, in the skin itself, and in various endogenous sources [2, 3]. The structure of skin is quite complex being composed of several layers, each of which plays a specific role and carries out different functions [4]. Each layer is equipped with its own arsenal of defense molecules, and the various systems differ from each other based on the layer's susceptibility to oxidative stress and its function. It is generally agreed that one of the major and important contributions to skin aging, skin disorders and skin diseases results from reactive oxygen species (ROS) [1, 5]. Due to the high occurrence of potential biological targets for oxidative damage, skin is very susceptible to such reactions. For example, skin is rich in lipids, proteins, and DNA, all of which are extremely sensitive to the oxidation process [6-8]. Elucidation of the mechanisms involved in skin oxidation and the examination of the defense systems may contribute to the understanding of skin aging and of the mechanisms involved in the various pathological processes of skin. This review addresses the antioxidant defense mechanism of the skin, the role it plays during the aging process, and the role skin has following exposure to oxidative stresses.
Article
The antioxidative activity of the dried pericarp and seed of Japanese pepper was studied. The ethyl acetate extract from the pericarp and the methanol extract from the seed showed strong antioxidative activity against linoleic acid by the ferric thiocyanate and thiobarbituric acid (TBA) methods. Japanese pepper contained 3.9 and 2.9 mg/100 g of dry weight (dw) of tocopherols in the pericarp and seed, respectively, alpha-Toc in the former constituting 82% of total tocopherol and gamma-Toc in the latter constituting 96%. Arbutin and magnoflorine were isolated as antioxidants and their chemical structures determined by instrumental analyses. The contents of arbutin evaluated as the trifluoroacetate derivative by GC-MS were 35 and 3.0 mg/100 g of dw in the pericarp and seed, respectively. Magnoflorine was present only in the seed, and not in the pericarp. Both arbutin and magnoflorine exhibited antioxidative activity against linoleic acid and radical-scavenging activity against the DPPH radical.
Article
Rapid scavenging of the model stable radical cation, ABTS(*+), has been applied to screen for the antioxidant activity of flavonoids. The reaction follows two distinct phases. For compounds with a monophenolic B-ring there is a rapid initial phase of reduction of ABTS(*+) within 0.1 s with no further change in the subsequent 2.9 s. In contrast, compounds with a catechol-containing B ring follow a fast initial scavenging phase with a slow secondary phase. Flavonoids with an unsubstituted B ring do not react within this time scale. The findings suggest that the structure of the B ring is the primary determinant of the antioxidant activity of flavonoids when studied through fast reaction kinetics.
Article
Radiation hazards in outer space present an enormous challenge for the biological safety of astronauts. A deleterious effect of radiation is the production of reactive oxygen species, which result in damage to biomolecules (e.g., lipid, protein, amino acids, and DNA). Understanding free radical biology is necessary for designing an optimal nutritional countermeasure against space radiation-induced cytotoxicity. Free radicals (e.g., superoxide, nitric oxide, and hydroxyl radicals) and other reactive species (e.g., hydrogen peroxide, peroxynitrite, and hypochlorous acid) are produced in the body, primarily as a result of aerobic metabolism. Antioxidants (e.g., glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, vitamin E, vitamin C, vitamin A, and tea polyphenols) and antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidases) exert synergistic actions in scavenging free radicals. There has been growing evidence over the past three decades showing that malnutrition (e.g., dietary deficiencies of protein, selenium, and zinc) or excess of certain nutrients (e.g., iron and vitamin C) gives rise to the oxidation of biomolecules and cell injury. A large body of the literature supports the notion that dietary antioxidants are useful radioprotectors and play an important role in preventing many human diseases (e.g., cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes). The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions.
Article
The 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS (radical +)) decolorization assay was applied to evaluate the stoichiometric radical scavenging activity of ascorbic acid (AA) and two AA derivatives, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and 2-O-alpha-D-glucopyranosyl-6-O-octanoyl-L-ascorbic acid (6-Octa-AA-2G). AA rapidly reacted with ABTS (radical +), and the reaction was completed within 10 min. In contrast, AA-2G and 6-Octa-AA-2G continuously reacted with ABTS (radical +), and the reaction was not completed after 2 h. The radical scavenging activity of AA-2G and 6-Octa-AA-2G in aqueous solutions at pH 4.0 and above was higher than that at pH 3.0, whereas AA showed no difference in the pH range 3 to 6. The amounts of ABTS (radical +) scavenged by one molecule of AA, AA-2G and 6-Octa-AA-2G after 2 h of reaction at pH 6.0 were approximately 2.0, 3.4 or 3.9 molecules, respectively. This study demonstrates that the quantity of ABTS (radical +) quenched by AA-2G and 6-Octa-AA-2G is superior to that of AA in a long-term reaction.
Article
Background/purpose: The aging process has been studied with fervor recently, given our shifting demographics. Since age's effects are so manifest in skin's appearance, structure, mechanics, and barrier function, it is not surprising that much effort has been placed in research to better understand them. Quantitative measurements permitted by bioengineering have allowed us to objectively and precisely study aging skin. These overviews piece together the immense amounts of information that have emerged from recent technological advances in dermatological research in order to develop a unified understanding of the quantitative effects of age on the skin. Methods: We performed a literature on age-related changes in blood flow, pH, skin thickness, and ultrasound imaging data, searching Pub-med, Em-Base, Science Citation Index, and the UCSF dermatological library's collection of books on the topic of aging skin. Results: Despite the many tools and techniques available for quantitative analysis of skin, age studies are often conflicting, especially in the areas of blood flow and skin thickness. Trends indicate that blood flow may decrease with age, especially in sites exposed to the environment. pH apparently varies little until the age of 70, after which it declines. Skin thickness data are difficult to interpret; while the stratum corneum is generally accepted to maintain its thickness during aging, dermal, epidermal, and whole skin thickness changes are controversial. Ultrasound reveals the appearance of a subepidermal low echogenic band that thickens with age, especially in environmentally exposed areas. Some studies also indicate the presence of an echogenic band in the lower dermis which thins with increased age. However, the whole dermis appears to become more echogenic in elderly people. Conclusion: Much remains to be done if we are to reach consensus on the effects of age on skin structure and function. Future studies would be benefited by increased standardization of skin sites tested, methodology, and increased sample size.
Article
The aim of this study was to characterize the antioxidant activity of three ascorbic acid (AA) derivatives O-substituted at the C-2 position of AA: ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S). The radical-scavenging activities of these AA derivatives and some common low molecular-weight antioxidants such as uric acid or glutathione against 1,1-diphenyl-picrylhydrazyl (DPPH) radical, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+), or galvinoxyl radical were kinetically and stoichiometrically evaluated under pH-controlled conditions. Those AA derivatives slowly and continuously reacted with DPPH radical and ABTS+, but not with galvinoxyl radical. They effectively reacted with DPPH radical under acidic conditions and with ABTS+ under neutral conditions. In contrast, AA immediately quenched all species of radicals tested at all pH values investigated. The reactivity of Trolox, a water-soluble vitamin E analogue, was comparable to that of AA in terms of kinetics and stoichiometrics. Uric acid and glutathione exhibited long-lasting radical-scavenging activity against these radicals under certain pH conditions. The radical-scavenging profiles of AA derivatives were closer to those of uric acid and glutathione rather than to that of AA. The number of radicals scavenged by one molecule of AA derivatives, uric acid, or glutathione was equal to or greater than that by AA or Trolox under the appropriate conditions. These data suggest the potential usage of AA derivatives as radical scavengers.
Article
Hyperpigmentation disorders of the skin are common and can be the source of significant psychosocial distress for patients. The most common of these disorders are melasma and postinflammatory hyperpigmentation. Sunscreen use and minimizing sun exposure are crucial in all cases. Topical applications are the mainstay of treatment and include phenols, retinoids, corticosteroids, and their combinations.
Article
During normal cellular activities, various processes inside of cells produce reactive oxygen species (ROS). Some of the most common ROS are hydrogen peroxide (H2O2), superoxide ion (O2⁻), and hydroxide radical (OH⁻). These compounds, when present in a high enough concentration, can damage cellular proteins and lipids or form DNA adducts that may promote carcinogenic activity. The purpose of antioxidants in a physiological setting is to prevent ROS concentrations from reaching a high-enough level within a cell that damage may occur. Cellular antioxidants may be enzymatic (catalase, glutathione peroxidase, superoxide dismutase) or nonenzymatic (glutathione, thiols, some vitamins and metals, or phytochemicals such as isoflavones, polyphenols, and flavanoids).
Article
There is growing interest in measuring the antioxidant status of plant tissues. This protocol describes the oxygen radical absorbance capacity (ORAC) assay, which measures antioxidant inhibition of peroxyl radical-induced oxidations and is a measure of total antioxidant capacity. The assay is performed in a microplate and is assessed with a 96-well multi-detection plate reader. Total antioxidant capacity of 64 experimental samples can easily be analyzed in 1 d. This assay is presented along with rapid assays for total phenolic content and total ascorbate content. Overall, these assays provide a general diagnostic tool of the antioxidant capacity in leaf tissue extracts.
Article
Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo.
Article
Skin lightening preparations are widely used in dermatology by persons of all Fitzpatrick skin types. Fitzpatrick skin types I-III require local pigment lightening for the treatment of hormonally induced melasma and postinflammatory hyperpigmentation caused by acne and trauma. Fitzpatrick skin types IV and darker have an even greater need for skin lightening for social reasons, as well as pigmentary changes that occur around the eyes, in the intertriginous areas, following dermatitis, or with acne and trauma. The gold standard dermatologic agent for skin lightening was hydroquinone, until regulatory agencies in Japan, Europe, and most recently in the United States questioned the safety of this substance. This has encouraged research into alternative agents to inhibit skin pigmentation such as retinoids, mequinol, azelaic acid, arbutin, kojic acid, aleosin, licorice extract, ascorbic acid, soy proteins, and N-acetyl glucosamine. The efficacy and safety of each of these ingredients is examined as possible topical alternatives to hydroquinone.
Article
The antioxidant activity of a provitamin C agent, 2-O-beta-D-glucopyranosyl-L-ascorbic acid (AA-2betaG), was compared to that of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and ascorbic acid (AA) using four in vitro methods, 1,1-diphenyl-picrylhydrazyl (DPPH) radical-scavenging assay, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(*+))-scavenging assay, oxygen radical absorbance capacity (ORAC) assay, and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis inhibition assay. AA-2betaG slowly and continuously scavenged DPPH radicals and ABTS(*+) in roughly the same reaction profiles as AA-2G, whereas AA quenched these radicals immediately. In the ORAC assay and the hemolysis inhibition assay, AA-2betaG showed similar overall activities to AA-2G and to AA, although the reactivity of AA-2betaG against the peroxyl radical generated in both assays was lower than that of AA-2G and AA. These data indicate that AA-2betaG had roughly the same radical-scavenging properties as AA-2G, and a comprehensive in vitro antioxidant activity of AA-2betaG appeared to be comparable not only to that of AA-2G but also to that of AA.
pH-dependent long-term
  • Tai J A Takebayashi
  • Yamamoto
Takebayashi J, Tai A, Yamamoto I. pH-dependent long-term
Antioxidant determinations by the use of a stable
  • J Takebayashi
J. Takebayashi et al. Blois MS. Antioxidant determinations by the use of a stable
Free radicals, antioxidants, and nutrition
  • Yz Fang
  • S Yang
  • G Wu
Topical treatments for melasma and postinflammatory hyperpigmentation
  • C B Lynde
  • J N Kraft
  • C W Lynde