Article

Could Honey Have a Place in Colitis Therapy? Effects of Honey, Prednisolone, and Disulfiram on Inflammation, Nitric Oxide, and Free Radical Formation

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Abstract

The purpose of this study was to investigate the potential therapeutic roles of honey, prednisolone and disulfiram in an experimental model of inflammatory bowel disease. Another aspect of the study was to find out whether these substances have any effect on nitric oxide (NO) and free radical production. After the induction of colitis with trinitrobenzene sulfonic acid in 64 male rats, physiological saline, honey, prednisolone and disulfiram enemas were applied to the rats once daily for 3 days (acute treatment groups) or 7 days (chronic treatment groups). Control groups received only saline enemas. Rats were killed on the 4th or 8th days and their colonic mucosal damage was quantitated using a scoring system. Acute and chronic inflammatory responses were determined by a mucosal injury score, histological examination and measurement of the myeloperoxidase (MPO) activity of tissues. The content of malonylaldehyde (MDA) and NO metabolites in colon homogenates was also measured to assess the effects of these substances on NO and free oxygen radical production. Estimation of colonic damage by mucosal injury scoring was found to be strongly correlated with the histologic evaluation of colon specimens. On the other hand, mucosal injury scores were not correlated with MPO, MDA or NO values. There were significant differences between the MPO results of chronic-control and chronic-honey groups, as well as chronic-control and chronic-prednisolone groups (p = 0.03 and p = 0.0007). The acute honey, prednisolone, and disulfiram groups had significantly lower MDA results compared to the acute control group (p = 0.04, p = 0.02, and p = 0.04). In terms of NO, there was no significant difference between the treatment and control groups. NO was found to have a strong relationship with MDA (p = 0.03) and MPO values (p = 0.001). On the other hand, MPO results were not found to be correlated with MDA values (p > 0.05). MPO activity is not directly proportional to the severity of the inflammation, but it may only determine the amount of neutrophil in the tissues. Inflammatory cells are not the sole intensifying factor in colitis. Therefore, mucosal injury scores may not correlate well with MPO activities. In an inflammatory state NO and MPO levels have a strong relationship, since NO is released from the neutrophils. In an inflammatory model of colitis, intrarectal honey administration is as effective as prednisolone treatment. Honey may have some features in the treatment of colitis, but this issue requires further investigation. Honey, prednisolone and even disulfiram also have some value in preventing the formation of free radicals released from the inflamed tissues. Prednisolone may also have some possible benefits in the inhibition of NO production in colitis therapy.

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... The abnormalities in diabetes mellitus usually seen are increased susceptibility of liver to oxidative stress and elevated levels of serum aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase (Bilsel et al. 2002;Leeds et al. 2009). Studies showed that pine honey restored the activities of hepatic CAT, GPx, and SOD in the liver of young and middle-aged rats (Gumieniczek 2005) and reduced hepatic damage in trichlorfon-administered male BALB/c mice, hepato protective effect in sheep administered carbon tetrachloride (CCl4) (Yao et al. 2011), STZ-induced diabetic rats and in common bile duct obstruction of rats (Erejuwa et al. 2012). ...
... Study on smokers supplemented with β-carotene is reported to exaggerate cancer risk (Heinonen and Albanes 1994). Beneficial effects of honey over other vitamins are that honey is devoid of pro-oxidant properties, comprises several bioactive constituents which may produce synergistic antioxidant effects, and does not require regeneration into active form (Köhler et al. 2011;Rodrigo et al. 2008), and honey can scavenge both free radicals like OONO−, O2•− and non-free radicals like NO (Estevinho et al. 2008;Bilsel et al. 2002), upregulates intracellular transcription factor Nrf2 moderately, and is capable of reducing inflammation by inhibiting the production of NO and prostaglandin E (2) (Kassim et al. 2011;Bilsel et al. 2002). ...
... Study on smokers supplemented with β-carotene is reported to exaggerate cancer risk (Heinonen and Albanes 1994). Beneficial effects of honey over other vitamins are that honey is devoid of pro-oxidant properties, comprises several bioactive constituents which may produce synergistic antioxidant effects, and does not require regeneration into active form (Köhler et al. 2011;Rodrigo et al. 2008), and honey can scavenge both free radicals like OONO−, O2•− and non-free radicals like NO (Estevinho et al. 2008;Bilsel et al. 2002), upregulates intracellular transcription factor Nrf2 moderately, and is capable of reducing inflammation by inhibiting the production of NO and prostaglandin E (2) (Kassim et al. 2011;Bilsel et al. 2002). ...
Chapter
Honey, a supersaturated concentrated solution with complex constituents, has been used as therapeutic agent since ancient times. Natural products have been used as a substitute for various conventional treatments and drug discoveries. Different in vivo and in vitro studies have shown properties of honey including antioxidant, antibacterial, anti-inflammatory, anti-cancerous, and much more. Therapeutic properties of honey greatly depend on its constituent composition which may vary based on various factors like species of bee, environmental conditions, type of flower, and processing methods. Oxidative stress due to cellular metabolism and other physio-biochemical activities of the body demand the necessity of antioxidants in diet which can be fulfilled by honey. Antioxidant and other biological properties of honey are greatly determined by the polyphenol composition. This chapter comprises honey composition, type, antioxidant properties, and antioxidant mechanism of honey according to different research studies.
... Honey might be a novel antioxidant in the gastrointestinal tract (GIT), liver, pancreas, kidney, reproductive organs, and plasma/serum (Erejuwa et al. 2012) and it has healing effects on the wound types like those of the abdominal wall and perineum (Almasaudi and Abbas 2017). In one study, intra-rectal honey administration was as effective as prednisolone treatment (Bilsel et al. 2002). Also, primary components of eggs have pro-and antiinflammatory properties and lecithin is a main component of egg white that has anti-inflammatory and restoration effects (Andersen 2015). ...
... This study showed that the inflammation status in the colon after acetic acid administration causes a significant increase in the TNF-α compared with normal tissues (Table 3). The effects of honey in IBD were studied by the Bilsel et al. and Mahgoub et al. in animal IBD models and they concluded that honey was effective in the treatment of IBD (Bilsel et al. 2002;Mahgoub et al. 2002). Bilsel et al. showed dose-dependent protection of honey against acetic acid-induced colonic damage (Bilsel et al. 2002). ...
... The effects of honey in IBD were studied by the Bilsel et al. and Mahgoub et al. in animal IBD models and they concluded that honey was effective in the treatment of IBD (Bilsel et al. 2002;Mahgoub et al. 2002). Bilsel et al. showed dose-dependent protection of honey against acetic acid-induced colonic damage (Bilsel et al. 2002). In Mahgoub et al.'s study, there was almost 100% protection with the highest dose of honey (5 g/kg) used, while glucose, fructose, sucrose; maltose mixture produced no significant protective effect (Mahgoub et al. 2002). ...
Article
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Egg and honey contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways and have effects on oxidative stress. In this study, the effects of egg white and honey against acetic acid-induced colitis were investigated in rats. Forty adult rats were divided into five groups (n = 7), group I (normal saline), group II (egg white), group III (honey), group IV (Asacol® 100 mg/ml used as a positive control), and group V (combination of honey and egg white 50:50 v/v). Medications (2 cc/day) were administered rectally for a period of 6 days after induction of colitis using 2% acetic acid. Animals were killed on day 7 and colonic biopsies were taken for histopathological scoring. The concentration of malondialdehyde (MDA) and TNF-α was measured on the samples of the colon tissue that were frozen in liquid nitrogen. At 1 week, the histological damage was severe, and the MDA and TNF-α were high throughout the study without any treatment. Honey decreased the TNF-α and MDA tissue levels towards normal levels significantly (P < 0.05). Combination of honey and egg white was not better than honey alone as an anti-inflammatory agent. In the animal model of ulcerative colitis, rectal administration of honey significantly reduced the colonic inflammation. The present study indicates that honey is efficacious in the acetic acid-induced rat colitis model, but these results require further confirmation in human studies and determination of active ingredients.
... Furthermore, ingestion of diluted natural honey showed reduction effect on concentrations of prostaglandins such as prostaglandin E2, prostaglandin F2α, and thromboxane B2 in plasma of normal individuals [43]. Bilsel et al. (2002) have proved that anti-inflammatory activity of honey was as effective as prednisolone, reference drug [44]. Further, honey has an antiinflammatory action free from adverse side effects [45] such as suppression of immune response and tissue growth, formation of ulcers in stomach, etc. ...
... Furthermore, ingestion of diluted natural honey showed reduction effect on concentrations of prostaglandins such as prostaglandin E2, prostaglandin F2α, and thromboxane B2 in plasma of normal individuals [43]. Bilsel et al. (2002) have proved that anti-inflammatory activity of honey was as effective as prednisolone, reference drug [44]. Further, honey has an antiinflammatory action free from adverse side effects [45] such as suppression of immune response and tissue growth, formation of ulcers in stomach, etc. ...
... Previous studies have demonstrated the possible effectiveness of natural honey for treating IBD in rat models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) or acetic acid. [38][39][40] Another widely used animal experimental colitis model is the dextran sulfate sodium (DSS) model. The TNBS and acetic acid colitis model shows symptoms close to human CD, while the DSS model has typical symptoms similar to UC patients. ...
... In a TNBS-induced CD model, manuka honey showed a marked improvement in colonic damage. 38,40 These results suggest that PVH protected rats against DSS-induced acute colitis symptoms, which might be an available and efficacious treatment strategy for preventing UC in humans. ...
Article
Honeys produced from medicinal plants hold great promise for human health. Herein, we determined the chemical composition and gastrointestinal protective effects of a novel monofloral honey from Prunella vulgaris (PVH). The physicochemical parameters (moisture, sugars, pH, protein content, diastase activity, and hydroxymethylfurfural) of the PVH samples met the criteria specified in European Union regulations and Chinese National Standards. Fifteen phenolic compounds were identified and quantified via high-performance liquid chromatography with a diode array detector and with time of flight tandem mass spectrometry detection (HPLC-DAD/Q-TOF-MS). Rosmarinic acid was found to be a potential marker for PVH identification. Using a dextran sulfate sodium (DSS)-induced acute colitis model, we demonstrated that the administration of PVH (5 g per kg b.w., p.o.) significantly decreased the disease activity index and mitigated colonic histopathological changes in rats. PVH also modulated the gut microbiota composition in the colitic rats, reversing the increase in the Bacteroidetes/Firmicutes ratio and restoring Lactobacillus spp. populations in DSS-challenged rats. The results of this study provide fundamental data on PVH, supporting its future application in the prevention of colitis.
... Honey Intrarectal honey administration is as effective as prednisolone treatment in an inflammatory model of colitis [73]. ...
... Surprisingly, nitric oxide was not remarkably reduced through the same period suggesting that resolving the inflammatory process in the colonic tissues were not associated with modulating inflammatory cytokines [73]. Likewise, chronic gastric ulcer in Wister rats feed with 2.5 g/kg of Manuka honey has been alleviated through promoting anti-inflammatory cytokine IL-10 and minimizing pro-inflammatory cytokines TNF-α, IL-1β and IL-6 [72]. ...
Article
Full-text available
Inflammation is the main key role in developing chronic diseases including cancer, cardiovascular diseases, diabetes, arthritis, and neurodegenerative diseases which possess a huge challenge for treatment. With massively compelling evidence of the role played by nutritional modulation in preventing inflammation-related diseases, there is a growing interest into the search for natural functional foods with therapeutic and preventive actions. Honey, a nutritional healthy product, is produced mainly by two types of bees: honeybee and stingless bee. Since both types of honey possess distinctive phenolic and flavonoid compounds, there is recently an intensive interest in their biological and clinical actions against inflammation-mediated chronic diseases. This review shed the light specifically on the bioavailability and bioaccessibility of honey polyphenols and highlight their roles in targeting inflammatory pathways in gastrointestinal tract disorders, edema, cancer, metabolic and cardiovascular diseases and gut microbiota.
... In the modern literature, honey has been documented to have antimicrobial activities [17], wound healing effects and use in tissue regeneration [18], gastrointestinal tract diseases [19,20], anti-diabetic effect [21], cardio protective effect [22][23][24], antioxidant effects [25,26], and anti-inflammatory effects [27][28][29]. ...
... The potential of honey to protect against brain membrane lipid peroxidation, suppression of nitric oxide activity, and protection of endogenous antioxidant glutathione has been reported by Zahiruddin et al., Bilsel et al.,and Oyefuga et al.,[18,29,30] corroborating the results obtained in this study. ...
Article
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Objectives: Honey contains phenolic acids and flavonoids, which are significant in developing drugs against neuroinflammation. The study was designed to evaluate the ameliorative potential of honey in lipopolysaccharides-induced neuroinflammation.Methods: Thirty male Wistar rats were divided into six groups, namely: the control group (10 mL/kg vehicle), the LPS only group (250 µg/kg), the honey (0.26, 0.31 and 0.36 g/kg) and the ibuprofen (100 mg/kg). LPS (250 µg/kg i.p) was administered for 7days followed by the treatment with honey and Ibuprofen for another 7days. Animals were assessed for memory impairment and anxiety levels using a Novel object recognition test (NORT), elevated plus maze (EPM), and open field test (OFT). Brain levels of pro-inflammatory cytokine level, acetylcholinesterase activity, and oxidative stress were determined. The neuronal alteration was assessed histologically using cresyl fast violet staining of the hippocampus, prefrontal cortex, and striatum.Results: Honey (0.31 and 0.36 g/kg) significantly ameliorated LPS-induced memory impairment on NORT and increased time spent in the open arm and increased the locomotor activity in the OFT. Honey significantly (p < 0.05) reduced LPS-induced elevation of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). It significantly reduced malondialdehyde and nitrite levels in mice brains and reversed depletion of reduced glutathione levels. Honey attenuated LPS-induced elevation of acetylcholinesterase activity in rat brains. Cresyl violet staining showed the restoration of neuronal organization and Nissl body distribution in the hippocampus, prefrontal cortex and striatum compared to the LPS only group.Discussion: Honey effectively ameliorated LPS-induced poor cognitive performance, anxiety, motor coordination responses to neuroinflammation, and oxidative stress.
... Honey reduces the activity of cytooxygenase-1 and cyclooxygenase-2, thus showing anti-inflammatory effects and demonstrates immunomodulatory activities, and furthermore, ingestion of diluted natural honey showed reduction effect on concentrations of prostaglandins such as prostaglandin F2, prostaglandin F2α, and thromboxane B2 in plasma of normal individuals 27 . Bilsel et al. (2002) have proved that anti-inflammatory activity of honey was as effective as prednisolone, reference drug 28 . Furthermore, honey has an anti-inflammatory action free from adverse side effects, such as suppression of immune response and tissue growth, formation of ulcers in stomach, etc 27,28 . ...
... Bilsel et al. (2002) have proved that anti-inflammatory activity of honey was as effective as prednisolone, reference drug 28 . Furthermore, honey has an anti-inflammatory action free from adverse side effects, such as suppression of immune response and tissue growth, formation of ulcers in stomach, etc 27,28 . ...
Article
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The current mode of treatment of various diseases that cause as result of tobacco products based on synthetic drugs is very expensive, insalubrious and also not obtainable to all patients, at the same time these drugs alters genetics and metabolic pathways and also shows great adverse side effects to many patients. Hence, a safe and effective alternative natural remedy is needed to prevent the disease development and progression. In this lookout, natural recipes are indeed healthy and good remedy in the treatment/management of diseases that cause as result of tobacco products and these natural herbs are affordable, accessible and effective without any adverse side effects. These seven wonderful natural recipes (Garlic, ginger, honey, carrots, aloe Vera, dates & corn) are considered to be the most significant ancient herbs that have been used as an herbal remedy for over 2500 years all over the world. Although this research is first of its kind, because there was no such research conducted by any researcher who combined these seven wonderful natural recipes as a therapeutics, however there were several similar earlier studies on one or combination of either these recipes which have shown a very remarkable and suitable alternative remedy in various diseases cure without any side effects. This juice extracts from seven wonderful natural recipes are of paramount important with an immense medical properties and health beneficial effects that treats cancer further complications, cleanse the nicotine & tar from lungs that cause as a result of tobacco uses, boost immune system, as well as serve as an antibiotic in the remedy of many ailments.
... Also, it heals abscesses and deep infected surgical wounds, especially those, do not respond to the usual therapy (Kassim et al., 2010;Hussein et al., 2011;Yao et al., 2011). Its healing activity is through enhancing new tissue growth through prevention of infection (Bilsel et al., 2002;Medhi et al., 2008). Honey was effective in treatment of ulcerative colitis induced by trinitrobenzene sulfonic acid (Bilsel et al., 2002) and acetic acid (Mahgoub et al., 2002). ...
... Its healing activity is through enhancing new tissue growth through prevention of infection (Bilsel et al., 2002;Medhi et al., 2008). Honey was effective in treatment of ulcerative colitis induced by trinitrobenzene sulfonic acid (Bilsel et al., 2002) and acetic acid (Mahgoub et al., 2002). The DSS-induced colitis model is a well appreciated and widely used model of inflammatory bowel disease because of its simplicity in induction of the three disease forms (acute, chronic, or relapsing). ...
Article
A decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of ulcerative colitis (UC). Recent evidence has suggested a role of honey in reducing colitis-induced inflammatory and oxidative stress markers. In this study, we examined whether the anti-inflammatory and anti-oxidative properties of honey have a beneficial effect on the enteric innervation and cellular proliferation of UC in rat. The colitis was induced in rats by dextran sodium sulphate (DSS). The effect of natural honey on induced colitis was assessed by the following parameters in colonic samples: tissue injury, inflammatory infiltration, interleukin-1β and -6, superoxide dismutase and reduced glutathione. In addition, the expression of tumour necrosis factor-α, inducible NO synthase, caspase-3, CD34, Ki67, S100, c-kit, and neuron-specific enolase were examined by immunohistochemistry. Compared to the DSS-induced colitis group, the honey-treated group had significantly improved macroscopic and microscopic scores and exhibited the down-regulation of oxidative, inflammatory, and apoptotic markers. In addition, up-regulation of intrinsic muscular innervation and epithelial cellular proliferation markers was detected. These results provide new insight into the beneficial role of natural honey in the treatment of DSS-induced colitis via the inhibition of colonic motor dysfunction and the inflammatory-oxidative-apoptotic cascade. In addition, the role of honey in epithelial regeneration was clarified.
... In addition, these authors found that the antibacterial activity of honey was greater than that which could be attributed to the sugar content of the honey. The antibacterial activity of honey has also been investigated for its potential use in reducing food-borne pathogens, 37 preventing catheter exit/entry site infection, 38 for the treatment of colitis, 39 or even to protect the gastric mucousin Helicobacter pylori induced inflammation. 40,41 The application of honey to wounds to animals in veterinary environments has also been noted. ...
Article
Full-text available
The majority of the Yemeni honey varieties are characterized by low moisture content, in addition to the various flora of Yemeni plant, which may not be found in many countries, which makes them of high medicinal importance and high monetary value. This study was carried out the effect of three types of Hadhrami honey: Somur, Sidr (Baghya) and Meria against the growth of some pathogenic bacteria (Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Enterobacter sp., Staphylococcus aureus, and Klebsiella sp.). The results revealed that that Sidr honey gave the highest antibacterial activity against all bacteria tested, whereas the Somur and Meria honey were not recorded activity for growth Klebsiella sp. and Meria honey was not recorded activity for growth E. coli, respectively. When the antibiotics compared to types of honey antimicrobial activity, it was observed that the antimicrobial effect of Sidr honey was better than Imipenem antibiotic effect against P. aeruginosa. The inhibition of the studied strains was dependent on the type of honey source. It is concluded that Yemeni honey could potentially be used as therapeutic agents against bacterial infection particularly to the tested microorganisms.
... In addition, the antibacterial activity of honey was greater than that attributed to the sugar content of the honey. The antibacterial activity of honey has also been investigated for its potential use in reducing food-borne pathogens [32], preventing catheter exit/entry site infection [33], for the treatment of colitis [34], or even to protect against gastric mucousin Helicobacter pylori-induced inflammation [35][36][37]. ...
Article
Objective This study evaluates the antibacterial activity of five natural substances (hot water extract of cinnamon sticks, peppermint, and lemon leaves, Egyptian local packed honey, and Yemeni Sidr honey) against some gram-positive and gram-negative bacteria. Materials and methods The well diffusion method was first used to evaluate the antibacterial effect of each of these tested natural products on the tested organisms. The minimal inhibitory concentration and the minimal bactericidal concentration were detected for the effective substances. The highly effective antimicrobial ones were chosen to investigate their effect on the tested organisms by graphing the bacterial growth curve of each bacterium before and after treatment. Results and conclusion The findings indicated lower antibacterial effect of the three plant extracts compared with both bee honey samples. Yemeni Sidr honey, local honey, and cinnamon extract were the more potent antibacterial agents, respectively. Minimal inhibitory concentration and minimal bactericidal concentration of these three natural substances ranged between 10 and 80% for the tested organisms. Bacterial growth curve indicated that honey had powerful antimicrobial activity that did not allow bacteria to grow, especially after treatment with Yemeni Sidr honey. The study recommends that herbal extracts and honeys could potentially be used as therapeutic agents against bacterial infection particularly on the tested microorganisms.
... Konsumsi madu dikaitkan dengan peningkatan aktivitas antioksidan dalam tubuh, baik pada manusia maupun hewan. 5,6,7 Selain antioksidan, madu juga memiliki aktivitas farmakologis lain, diantaranya sebagai antibakteri, 8,9,10 antimutagenik dan antitumor, 11,12 antiinflamasi, 13,14 penurun kadar kolesterol, 15 dan vasodilator. 16,17 Aktivitas antioksidan madu dapat bervariasi, tergantung pada sumber bunganya. ...
Article
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Background. Many diseases resulted from degenerative processess which can be inhibited by antioxidant systems. Honey is one of food with antioxidant activity. Objective. This study aims to investigate antioxidant activities of several types of monofloral honey from Java and Sumatera. Method. A laboratory experimental study, conducted on 4 types of floral honeys: coffee, palm trees, cottonwoods and rambutan. Determination of phenolic compounds was performed with High Performance Liquid Chromatography (HPLC) and measurement of total phenolic contents performed with Folin-Ciocalteu's reagent. Antioxidant activity was conducted in two ways, those were by 2.2-diphenyl-1-picrylhydrasyl (DPPH) free radical scavenging method and linoleic acid peroxidation method using butylated hydroxytoluene(BHT) as a standard. Data were analyzed using Analysis of varian (Anova) and continued with Duncan's multiple range test (DMRT). Result. Four types of Javanese and Sumateranese honeys contained some phenolic compounds. Those are chlorogenic acid, cafeic acid, ρ-coumaric acid, ferulic acid, pinobanksin, quercetin, luteolin, pinocembrin and chrysin while the dominant fenolic compound varies between honeys. Total phenolic contents from four types of honey were between 2.000 to 4.400 ppm. The highest phenolic content was in honey from cottonwoods, but the best antioxidant activity was found in honey from coffee. Antioxidant activities were found in honey which come from the following order: coffee, cottonwoods, palm trees, and rambutan honey. Antioxidant activities did not correlated with total phenolic content. Conclusion. Javanese and Sumateranese honey contained nine active substances that varies in total phenolic contents. The best antioxidant activity was found in coffee honey, and this activity did not correlated with its total phenolic contents. ABSTRAK Latar Belakang. Banyak penyakit yang dapat timbul karena proses degeneratif yang dapat diperlambat dengan adanya sistem antioksidan. Madu merupakan salah satu bahan pangan yang diketahui memiliki aktivitas antioksidan. Tujuan. Penelitian ini bertujuan untuk mengetahui aktivitas antioksidan berbagai jenis madu dari beberapa daerah di Jawa dan Sumatera. Metode. Penelitian laboratorium terhadap empat jenis madu yaitu madu bunga kopi, sawit, randu dan rambutan. Penentuan kandungan komponen fenolat dilakukan dengan High Performance Liquid Chromatography (HPLC) dan pengukuran kadar fenolat total dilakukan dengan reagen folin-ciocalteu. Aktivitas antioksidan diukur berdasarkan peredaman radikal bebas 2.2-diphenyl
... At day 15, plasma concentrations of thromboxane B(2), PGE(2) and PGF(2α) decreased by 48%, 63% and 50%, respectively. The ingestion of honey decreased inflammation in an experimental model of inflammatory bowel disease in rats [87]. ...
... Helicobacter pylori [15]. The healing properties of honey can be ascribed to the fact that it offers antibacterial activity, maintains a moist wound environment that promotes healing, and has a high viscosity which helps to provide a protective barrier to prevent infection [16]. Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound [17,18] demonstrated anti-inflammatory effects of honey in human after ingestion of honey [19]. ...
Article
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The global prevalence of chronic diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer and Alzheimer's disease is on the rise. These diseases constitute the major causes of death globally. Honey is a natural substance with many medicinal properties such as antibacterial, hepatoprotective, hypoglycemic, reproductive, and antihypertensive and antioxidant. This review presents findings that indicate honey may ameliorate oxidative stress in the gastrointestinal tract (GIT), liver, pancreas, kidney, reproductive organs and plasma/serum. Besides, the review highlights data that demonstrate the synergistic antioxidant effect of honey and antidiabetic drugs in the pancreas, kidney, and serum of diabetic rats. These data suggest that honey, administered alone or in combination with conventional therapy, might be a novel antioxidant in the management of chronic diseases commonly associated with oxidative stress. In view of the fact that the majority of these data emanate from animal studies, there is an urgent need to investigate this antioxidant effect of honey in human subjects with chronic or degenerative diseases.
... Honey has been reported to have immunomodulatory activities (14) and is able to repair wound tissues by modulating the activity of monocyte cells and releasing antiinflammatory cytokines (15). The role of honey in the treatment of rats bowel inflammation was investigated (16). The anti-inflammatory effects are due to a depletion in plasma concentrations of thromboxane B 2 , prostaglandin E 2 (PGE 2 ), and PGF 2α , as well as the synergic effect of the phenolic compounds identified in the honey (17,18). ...
Article
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Background: Honey as a natural product exhibits a variety of biological and pharmacological activities. Its anti-inflammatory, antioxidant, antibacterial, and antihypertensive effects have already been proven. Objectives: In this study, the inhibitory effects of honey on the 7,12-dimethylbenz(a)anthracene-initiated and croton oil-promoted mice skin carcinogenesis were studied. Methods: Albino Swiss mice were pretreated with multiple topical applications of honey. After nine hours, the carcinogenesis was initiated by a single dose of DMBA. Topical croton oil, as for a promoting agent, was applied biweekly for a period of 30 weeks. Results: The tumor incidences were observed. Compared to the control group, the honey pre-treated mice showed a significant inhibition in tumor incidences. In addition, the enhanced uptake of [³H]-thymidine in mice skin DNA was inhibited in honeypretreated animals as compared to the control group. Furthermore, honey significantly decreased croton oil-mediated lipid peroxidation (LPO). Conclusions: Taken together, the results suggest that the antioxidants existed in honey have diminishing effects on croton oilmediated murine skin tumor promotion. In conclusion, we suggest that honey as an effective natural preventive agent may provide protection against skin cancer. © 2018, Jundishapur Journal of Natural Pharmaceutical Products.
... In addition, these authors found that the antibacterial activity of honey was greater than that which could be attributed to the sugar content of the honey. The antibacterial activity of honey has also been investigated for its potential use in reducing food-borne pathogens, 37 preventing catheter exit/entry site infection, 38 for the treatment of colitis, 39 or even to protect the gastric mucousin Helicobacter pylori induced inflammation. 40,41 The application of honey to wounds to animals in veterinary environments has also been noted. ...
Article
The majority of the Yemeni honey varieties are characterized by low moisture content, in addition to the various flora of Yemeni plant, which may not be found in many countries, which makes them of high medicinal importance and high monetary value. This study was carried out the effect of three types of Hadhrami honey: Somur, Sidr (Baghya) and Meria against the growth of some pathogenic bacteria (Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Enterobacter sp., Staphylococcus aureus, and Klebsiella sp.). The results revealed that that Sidr honey gave the highest antibacterial activity against all bacteria tested, whereas the Somur and Meria honey were not recorded activity for growth Klebsiella sp. and Meria honey was not recorded activity for growth E. coli, respectively. When the antibiotics compared to types of honey antimicrobial activity, it was observed that the antimicrobial effect of Sidr honey was better than Imipenem antibiotic effect against P. aeruginosa. The inhibition of the studied strains was dependent on the type of honey source. It is concluded that Yemeni honey could potentially be used as therapeutic agents against bacterial infection particularly to the tested microorganisms.
... The inhibitory effect of honey on carcinogenesis can be attributed to the presence of its active components, especially flavonoids and phenolic constituents. Honey plays an important role in preventing inflammatory tissues from producing free radicals [42] . Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidant, antiinflammatory, antiviral action, antiproliferative effect, apoptosisinducing effect and anticancer effect [4346] . ...
... The administration of disulfiram, given its mechanism of action, could induce nausea and vomiting [60]. Nevertheless, disulfiram has been shown to prevent free radicals' production from inflamed tissues [61]. On this basis, disulfiram could be administered in patients with inflammatory bowel disease. ...
Article
Introduction: Alcohol Use Disorder (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a "temporary recommendation for use" in France. Areas covered. The safety of the medications mentioned above on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed. Expert opinion. Mechanism of action and metabolism of these drugs as well as patients' clinical characteristics can affect the safety of treatment. All approved medications are valid tools for the treatment of AUD in patients without advanced liver disease. For some drugs, attention should be paid to patients with renal failure and medications may be used with caution, adjusting the dosage according to kidney function. In patients with AUD and advanced liver disease, at present only baclofen has been formally tested in randomized controlled trials showing its safety in this population.
... Laboratory studies have shown that pure honey has significant antibacterial activities against the major wound-infecting species [14,15], especially those with the potential to develop antibiotic resistance such as Methicillin-Resistant (MRSA), ß-haemolytic streptococci, Vancomycin Resistant Enterococci (VRE) and species [16,17]. The antibacterial activity of honey has also been investigated and reported for its potential use in reducing food-borne pathogens [18]; preventing entry site of infection [19]; for the treatment of colitis [20]. The application of honey to wounds of animals in veterinary environments has also been noted [7]. ...
... Blood thromboxane and PGF2α were reduced in response to ingestion of 70 g of honey (Al-Waili and Boni 2003). In addition, the anti-inflammatory effect of honey has also been observed in inflammatory bowel disease (Bilsel et al. 2002). The anti-inflammatory effect has been linked to the reduction of free radicals produced at the site of inflammation and antibacterial or direct anti-inflammatory effect. ...
Article
Full-text available
Honey is a bee-derived supersaturated solution composed of complex contents mainly glucose, fructose, amino acids, vitamins, and minerals. Composition of honey may vary due to the difference in nectar, season, geography, and storage condition. Honey has been used since times immemorial in folk medicine and has recently been rediscovered as an excellent therapeutic agent. In the past, honey was used for a variety of ailments without knowing the scientific background and active ingredients of honey. Today, honey has been scientifically proven for its antioxidant, regulation of glycemic response, antitumor, antimicrobial, anti-inflammatory, and cardiovascular potentiating agent. It can be used as a wound dressing and healing substance. Honey is different in color, flavor, sensory perception, and medical response. Apart from highlighting the nutritional facts of honey, we collected the finding of the published literature to know the mechanism of action of honey in different diseases. This review covers the composition, physiochemical characteristics, and some medical uses.
... 113 Recently, it is revealed that intrarectal administration of honey is effective in treating colitis. 114 Honey on one hand inhibits more than sixty different pathogenic bacterial species and on the other hand enhances the growth of beneficial gastrointestinal tract flora. 115,116 Recently, Olofsson and Vásquez have discovered a unique lactic acid bacterial microbiota in honey bee stomach, which is also present in large quantities in fresh honey. ...
Article
Background: The development of bacterial resistance to antibiotics has made it more difficult and expensive to treat infections. Honey is getting worldwide attention as a topical therapeutic agent for wound infections and potential future candidate for systemic infections. Objectives: The purpose of this review was to summarise different antibacterial bio-active compounds in honey, their synergistic interaction and their clinical implications in topical and systemic infections. In addition, contemporary testing methods for evaluating peroxide and non-peroxide antibacterial activity of honey were also critically appraised. Design: MEDLINE, EMBASE, Cochrane Library, Pub Med, reference lists and databases were used to review the literature. Results: Honey contains several unique antibacterial components. These components are believed to act on diverse bacterial targets, are broad spectrum, operate synergistically, prevent biofilm formation, and decrease production of virulence factors. Moreover, honey has the ability to block bacterial communication (quorum sensing), and therefore, it is unlikely that bacteria develop resistance against honey. Bacterial resistance against honey has not been documented so far. Unlike conventional antibiotics, honey only targets pathogenic bacteria without disturbing the growth of normal gastrointestinal flora when taken orally. It also contains prebiotics, probiotics, and zinc and enhances the growth of beneficial gut flora. The presence of such plethora of antibacterial properties in one product makes it a promising candidate not only in wound infections but also in systemic and particularly for gastrointestinal infections. Agar diffusion assay, being used for evaluating antibacterial activity of honey, is not the most appropriate and sensitive assay as it only detects non-peroxide activity when present at a higher level. Therefore, there is a need to develop more sensitive techniques that may be capable of detecting and evaluating different important components in honey as well as their synergistic interaction. Conclusions: Keeping in view the current guidelines for treatment of diarrhea, honey is considered one of the potential candidates for treatment of diarrhea because it contains a natural combination of probiotics, prebiotics, and zinc. Therefore, it would be worthwhile if such a combination is tested in RCTs for treatment of diarrhea.
... Ingestion of honey had a positive effect in an experimental model of inflammatory bowel disease in rats 62 . Honey administration is as effective as prednisolone treatment in an inflammatory model of colitis. ...
... In wounds with no bacterial infection, honey proved to exhibit anti-inflammatory activity (Postmes, 2001). Honey intake by rats with bowel disease was an efficient treatment for inflammatory colitis, possibly due to the prevention of free radicals production that, according to the researchers, could be also indirectly related to the antibacterial activity of this food (Bilsel et al., 2002). Kassim, Achoui, Mansor, and Yusoff (2010) and Kassim, Achoui, Mustafa, Mohd, and Yusoff (2010) showed that in rats both honey and its extracts could inhibit edema, producing inhibitory activities against inflammatory mediators. ...
Article
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Honey is a natural sweetener with a complex composition. Honey features vary depending on the botanical source and geographical origin, as well as climatic, processing and storage conditions. Honey is mainly composed of carbohydrates and water, parameters that influence its shelf life and some of its properties, including color, flavor, density, viscosity, hygroscopicity, and crystallization. Honey also contains small amounts of other components, such as nitrogen compounds, organic acids, minerals, vitamins, Maillard reaction products, volatile compounds, and several bioactive substances that affect sensory and physical characteristics, as well as biological potential. This review summarizes the literature about the composition and main properties of honey. It also describes the use of honey as a biomonitor for collecting information about the environment, identifying environmental contamination and assessing the level of soil, water, plant and air pollution.
... Anti-inflammatory and the non-steroidal medicines are quite dangerous to cells or organelles, specifically in the stomach. Honey possesses an antiinflammatory effect and unveiling no adversarial effects(107,61). ...
Article
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Honey is a natural domestic sweet food material and chemically diverse superfluous product of nectar acquired from flowers. Owing to the presence of higher amounts of antioxidant compounds covering phenolic, enzymes, organic acids and bioactive peptides, holds a strong ability to prevent various maladies. In addition, honey has also been exploited in certain cardiovascular, gastrointestinal, neoplastic and inflammatory states along with its role in treatment of copious infections and surgical wounds. Flavonoids and polyphenols are important bioactive components present in honey and have antioxidant properties. Some bioactive compounds, for example luteolin, galangin, isorhamnetin, quercetin and kaempferol are present in honey. Phenolic acids and flavonoids have important pharmacological activities such as anti-allergic, anti-biotic, anti-carcinogenic and hypoglycemic. Moreover, curative potential of bioactive components and their utilization in value added food products are also the limelight of article.
... It contains enzymes like glucose oxidase, diastase, invertase, catalase, and peroxidase. Honey also contains many other bioactive constituents such as organic acids, ascorbic acid, trace elements, vitamins, amino acids, proteins and Maillard reaction products [16][17][18][19][20]. ...
... Helicobacter pylori [15]. The healing properties of honey can be ascribed to the fact that it offers antibacterial activity, maintains a moist wound environment that promotes healing, and has a high viscosity which helps to provide a protective barrier to prevent infection [16]. Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound [17,18] demonstrated anti-inflammatory effects of honey in human after ingestion of honey [19]. ...
... The results confirmed that honey polyphenols can improve these parameters related to oxidative stress, which was consistent with a similar study on trinitrobenzene sulfonic acid-induced colitis showing that honey treatment prevented the formation of free radicals released from the inflamed tissues. [46] Improving cell antioxidant capacity and intestinal oxidative stress provides us with another explanation for the anti-colitis activity of honey polyphenols. ...
Article
Scope: Ulcerative colitis (UC) is a multifaceted and recurrent immune disorder that requires long-term potent pharmacological treatment. Honey, as a natural food of nourishment and pharmaceutical value, has been found to defend against colitis. Methods and results: We investigated the effects of different constituents in honey on dextran sulfate sodium (DSS)-induced colitis in rats. Rats were given DSS, sugars, honey, polyphenols or SASP for a week, with blood and colon samples collected for the biochemical parameters and inflammation-related gene analysis and colon contents for gut microbiota. The results showed that pretreatments with honey polyphenols significantly improved SOD, GSH-Px, NO, and MPO levels and reduced DSS-induced colonic apoptosis, the colonic inflammatory cytokines IL-6, TNF-α and TGF-β1 accompanied by downregulation of IL-1β, IL-6, TNF-α, IFN-γ gene and upregulation of IκB-α gene. Furthermore, honey polyphenols and SASP showed similar microbial community structure shifts and selective enrichment of key species. At the genus level, honey polyphenols significantly reduced the population of Bacteroides, Corynebacterium, and Proteus species. The correlation analysis indicated that colonic gene expression regulated by honey polyphenols was relative to the key species of gut microbiota. Conclusions: Honey polyphenols improved intestinal inflammation and oxidative stress resistance via modulating gut microbiota, which was conducive to revealing the host-microbe interactions. This article is protected by copyright. All rights reserved.
... Topical honey has also been used successfully in a comprehensive treatment of diabetic ulcers when the patient cannot use topical antibiotics [55]. The nonperoxide antibiotic activity is due to methylglyoxal (MGO) and unidentified synergistic effects. ...
... More recently, the therapeutic value of honey in modern human medicine has emerged as a topic of interest, especially in light of the increasing prevalence of antimicrobial resistance globally 2 . There is evidence in the scientific literature supporting the use of honey as an antimicrobial, anti-inflammatory, and anti-tumour agent [3][4][5][6] . Honey has also been critically examined for its potential in humans as a therapeutic agent in burns and wound healing, as a cardiovascular potentiating agent, and for regulation of glycemic response 1 . ...
... Acetaldehyde dehydrogenase is responsible for the main source of ROS in colon (Sharon and Stenson, 1984), and the activity of ROS in tissues can be reflected in the level of molondialdehyde (MDA) when membrane lipids are damaged (Ohkawa et al., 1979). DSF can reduce MDA levels in the colonic tissues of rats with colitis (Bilsel et al., 2002). This may be due to the fact that DSF is the inhibitor of acetaldehyde dehydrogenase (Sawczenko and Sandhu, 2003;Gupta et al., 2008), however, the exact mechanism is still unclear. ...
Article
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Disulfiram has been used clinically for decades as an anti-alcoholic drug. Recently, several studies have demonstrated the anti-inflammatory effects of disulfiram and its metabolism, which can alleviate the progression of inflammation in vivo and in vitro . In the current study, we summarize the anti-inflammatory mechanisms of disulfiram and its metabolism, including inhibition of pyroptosis by either covalently modifying gasdermin D or inactivating nod-like receptor protein 3 inflammasome, dual effects of intracellular reactive oxygen species production, and inhibition of angiogenesis. Furthermore, we review the potential application of disulfiram and its metabolism in treatment of inflammatory disorders, such as inflammatory bowel disease, inflammatory injury of kidney and liver, type 2 diabetes mellitus, sepsis, uveitis, and osteoarthritis.
... The high concentrations of honey sugar and low pH value are responsible for antibacterial activity. Many studies have confirmed that honey has anti-inflammatory (Kouchesfahani et al., 2010;Al-Waili and Boni, 2003;Al-Waili, 2003;Al-Waili, 2004;Bilsel et al., 2002), immunomodulatory and antitumor activity (Abuharfeil et al., 1999;Al-Waili, 2003;Chepulis, 2007;Othman 2012;Orsolic and Basic, 2004;Wen et al., 2012). It was found that a diet enriched with honey can reduce the level of malignant processes of breast, prostate, endometrium (Tsiapara et al., 2009). ...
Conference Paper
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The research aims to obtain the results of the impact of an application of microbial fertilizers in combination with mineral fertilizers on the health and chemical composition of tomatoes. The study was conducted in 2013 and 2014 on the basic experimental plots in two variants (1. inorganic fertilizer and chemical crop protection + microbial fertilizer Slavol, 2. inorganic fertilizer and chemical crop protection-control). In the year 2013, there was no significant presence of diseases and pests, except for the occurrence of Tetranychus urticae. In early June 2014, the symptoms of Phytophthora infestans appeared only in the control variant. In both years of the study, the average total soluble solids, total acidity, and content of N, Mg, K, Cu were higher in the variant with applied microbial fertilizer. Content of nitrates, lycopene, P, Fe and Zn varied depending on the year and treatment. The application of microbial fertilizer has contributed to better health, and the contents of some tomato fruit quality parameters were increased. Key words: tomato, Slavol, diseases, pests, quality
... Honey has been shown to have anti-microbial, anti-oxidant, and anti-inflammatory bioactivities (Bogdanov et al., 2008;Samarghandian et al., 2017). As evidence of its anti-inflammatory activities, honey has been found to reduce inflammation and neutrophil infiltration in the colon in trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats (Bilsel et al., 2002;Prakash et al., 2008). The phenolic extract of honey inhibits expression of the Tnf and Ilb genes induced by LPS in N13 microglial cells (Candiracci et al., 2012). ...
Article
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Honey has been used as a nutrient, an ointment, and a medicine worldwide for many centuries. Modern research has demonstrated that honey has many medicinal properties, reflected in its anti‐microbial, anti‐oxidant, and anti‐inflammatory bioactivities. Honey is composed of sugars, water and a myriad of minor components, including minerals, vitamins, proteins and polyphenols. Here, we report a new bioactive component‒vesicle‐like nanoparticles‒in honey (H‐VLNs). These H‐VLNs are membrane‐bound nano‐scale particles that contain lipids, proteins and small‐sized RNAs. The presence of plant‐originated plasma transmembrane proteins and plasma membrane‐associated proteins suggests the potential vesicle‐like nature of these particles. H‐VLNs impede the formation and activation of the nucleotide‐binding domain and leucine‐rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, which is a crucial inflammatory signalling platform in the innate immune system. Intraperitoneal administration of H‐VLNs in mice alleviates inflammation and liver damage in the experimentally induced acute liver injury. miR‐4057 in H‐VLNs was identified in inhibiting NLRP3 inflammasome activation. Together, our studies have identified anti‐inflammatory VLNs as a new bioactive agent in honey.
... It also contains folate, niacin, pantothenic acid, riboflavin, vitamin C, pyridoxine, proteins, minerals, pinocembrin, hesperetin, quercetin, chrysin, apigenin, galangin, kaempferol, ellagic acid, ferulic acid, p-coumaric acid, and caffeic acid (Allsop and Miller 1996, Eteraf-Oskouei and Najafi 2013, Zumla and Lulat 1989. Scientific studies have revealed that honey includes anti-inflammatory, antioxidant, wound healing, antidiabetic, antibacterial, and antifungal activities (Aljadi and Kamaruddin 2004, Al-Mamary et al. 2002, Al-Waili 2005, 2004, Al-Waili and Boni 2003, Asadi-Pooya et al. 2003, Bansal et al. 2005, Beretta et al. 2005, Bilsel et al. 2002, Blasa et al. 2006, Brady et al. 1996, Chepulis 2007, Chua et al. 2013, Efem 1988, Frankel et al. 1998, Gheldof and Engeseth 2002, Jeffrey and Echazarreta 1996, Meda et al. 2004, Molan 1999, Obaseiki-Ebor and Afonya 1984, Olaitan et al. 2007, Schramm et al. 2003, Shimazawa et al. 2005, Yaghoobi et al. 2008. ...
... In this present study, it was found that honey at both high and low doses, had no effect on the serum level of PG E 2 . This is in contrast to the findings of an in vivo study which reported that Gelam honey and its extract have antiinflammatory effects by reducing the inflammatory mediators such as PG E 2 in rat paw tissue [31]. Also, Saba et al., found that Gelam honey significantly reduced the production of serum PG E 2 [16]. ...
Article
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Background: Clinically, osteoarthritis manifests as joint pain with concomitant loss of joint function, which may ultimately result in a substantially reduced quality of life for the patient. Although, a lot is known about the symptom of the disease, the pathophysiology behind the structural changes is complex and poorly understood. By understanding the mechanisms driving joint tissue destruction in osteoarthritis and identifying the key factors involved, new targets for therapy are emerging that will go beyond symptomatic relief to slowing or stopping the progression of osteoarthritis. Aim: Thus, the aim of this study was to evaluate the effect of honey on disease progression, pain perception and inflammation in monosodium iodoacetate (MIA)-induced knee osteoarthritis in female Wistar rats. Methods: Thirty, twelve-month old female Wistar rats, weighing between 200 g & 250 g, were randomly divided into five groups of six animals each. Animals in group one were not induced and served as the control, while animals in groups two to five were injected with monosodium iodoacetate in the right knee. In addition, animals in group two received normal saline (1 ml/kg b.w.), group three received arthocare (glucosamine/chondroitin sulphate 6.67/8.33 mg/kg b.w.), group four received low dose honey (250 mg/kg b.w.) while group five received high dose honey (1,000 mg/kg b.w.) and were treated for twenty one days. All animals were subjected to assessment of tactile allodynia (von Frey test), acute inflammation (knee edema), and serum biomarkers: tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), prostaglandin E2 (PG E2) & cartilage oligomeric matrix protein (COMP) as well as histo-pathological assessment of the right knee joint. Results: Honey (at high and low doses), significantly (p
... Honey reduces the inflammation in various diseases without having any major side effects (Vallianou et al. 2014). Several studies report that honey exhibits inflammatory response in several clinical trials, animal models and cell cultures (Al-Waili 2003;Candiracci et al. 2012;Leong et al. 2012;Bilsel et al. 2012). ...
Chapter
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Honey comes with a legendary history of being used as an indigenous medicine to cure a number of diseases. Honey is an essential source of phenolic molecules such as flavonoids and phenolic acids. The most abundant flavonoids present in honey include flavones, flavanones, and flavonols. Flavonoids show diverse activities such as non-inflammatory, antiallergenic, antiviral, antimalignant, antimicrobial, however, the antioxidant activity has been studied widely. Honey also possess a diverse molecules of phenolic acids including p-coumaric, ferulic, caffeic acid, acetophenones, phenylacetic acids, syringic, vanillic, gallic acid, and so on which endow it with the therapeutic activities against pathogens, inflammation while at the same time shows antioxidant and healing properties. The phenolic compounds owing to their medical properties make honey a very critical and attractive prophylactic entity for the prevention of chronic diseases associated with oxidative stress including cancer, cardiovascular disease, diabetes, respiratory disease, hypertension, neurodegenerative diseases etc. In this chapter, a discussion has been made on classification, structure, and medicinal and health benefits of phenolic compounds.
... Laboratory studies have shown that pure honey has significant antibacterial activities against the major wound-infecting species [14,15], especially those with the potential to develop antibiotic resistance such as Methicillin-Resistant (MRSA), ß-haemolytic streptococci, Vancomycin Resistant Enterococci (VRE) and species [16,17]. The antibacterial activity of honey has also been investigated and reported for its potential use in reducing food-borne pathogens [18]; preventing entry site of infection [19]; for the treatment of colitis [20]. The application of honey to wounds of animals in veterinary environments has also been noted [7]. ...
Article
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Antibacterial activities of the two honey samples, produced by the honeybee (Apis mellifera), were assayed using standard well diffusion method. Both honey samples were tested at four concentrations (5%, 25%, 50% and 100% w/v) against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, Bacillus subtilis and Escherichia coli, and mean zones of inhibition were measured. Both honey samples used were effective in inhibiting the growth of the test organisms at 25-100% concentrations (w/v). No honey sample was inhibitory at 5% concentration (w/v). The inhibitory effect of undiluted concentration of the honey samples (100% w/v) on Escherichia coli was comparable to that of Amoxicillin (20.0 ± 0.1 mm) and Chloramphenicol (17.5 ± 0.2 mm). Tetracycline had a very low inhibitory effect on the test organisms. In conclusion, natural honey can be employed in treating some common diseases especially those caused by the tested microorganisms and carries the potential of introducing new template into modern medicine.
... The high concentrations of honey sugar and low pH value are responsible for antibacterial activity. Many studies have confirmed that honey has anti-inflammatory (Kouchesfahani et al., 2010;Al-Waili and Boni, 2003;Al-Waili, 2003;Al-Waili, 2004;Bilsel et al., 2002), immunomodulatory and antitumor activity (Abuharfeil et al., 1999;Al-Waili, 2003;Chepulis, 2007;Othman 2012;Orsolic and Basic, 2004;Wen et al., 2012). It was found that a diet enriched with honey can reduce the level of malignant processes of breast, prostate, endometrium (Tsiapara et al., 2009). ...
Article
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Persimmon is beloved fruit of warmer southern European areas. It is edible when it softens and astringency is naturally removed but many consumers want to eat hard fruits with astringency removed artificially. Astringency from the hard fruits can be removed by several methods of which exposure to extreme concentrations of CO2 (>90%) seem to be the most user friendly. In this study, we investigated the effect of extreme CO2 concentrations on astringency removal, taste, soluble solids and fruit flesh firmness. Our results show astringency removal can be sufficiently initiated by 24-hour exposure to extreme CO2 concentrations and process is finished within the next three days. Lower CO2 concentrations (70%) need some longer exposure but may have benefit in taste. We observed temporal decrease of soluble solids in the CO2 exposed persimmon fruits probably due to fixation of the astringent soluble tannins. Following changes in fruits flesh firmness during and after exposure to extreme CO2 concentrations reveal a temporal increase in exposed fruits followed by a slower softening process.
... The limited use of honey in modern therapy is based on the lack of scientific data (Ali et al. 1991). With recent research, it was found that honey is an enigmatic gel with several health benefits including antioxidant (Jeffrey and Echazarreta 1996;Ahmed and Othman 2013), wound healing and antibacterial activity (Medhi et al. 2008), anti-fungal (Tonks et al. 2003), anti-inflammatory (Al-Waili and Boni 2003), gastroprotective (Ezz El-Arab et al. 2006), cardioprotective (Khalil and Sulaiman 2010), hepatoprotective (Meda et al. 2004;Al-Waili 2003b;Kilicoglu et al. 2008), antidiabetic (Al-Waili 2004Bansal et al. 2005) and antihypertensive (Bilsel et al. 2002), and many more. There are a lot of reports suggesting the free radical scavenging property of honey (Beretta et al. 2007). ...
Chapter
Neurodegenerative disorder is the major age-related problem with no specific cure. The drugs available in the market relieve the severity of the disease and increase the average life span. There is always room for more novel therapeutic strategies for the prevention of neurodegenerative diseases. Honey has been used since ages for various disease prevention, and recently it has been used to combat these diseases too. The flavonoids and the phenolic acids of honey have preventive effects and have been known to exhibit antioxidant, anti-inflammatory, and anti-apoptotic effects. These phytochemicals can prevent the neurodegeneration via NAD pathway where they are responsible for inhibiting CD38, PARP and activating SIRT1 overall by increasing the concentration of NAD in the neurons. With an increase in the amount of NAD, Sirtuins can be activated which protects age-related neurodegenerative diseases. Therefore, honey can be used as “NAD compounds” in clinics but with further mechanistic research.
... Antiinflammatory activity of honey was as effective as prednisolone, reference drug. It was proved that honey has an anti-inflammatory action free from adverse side effects such as suppression of immune response and tissue growth, formation of ulcers in stomach, etc. 46 Another study investigated the potential protective effect of a honey flavonoid extract (HFE) on the production of proinflammatory mediators by lipopolysaccharide-stimulated N13 microglia. The results demonstrate that HFE significantly inhibited the release of pro-inflammatory cytokines such as TNFα and IL-1β. ...
Article
Children are more susceptible to various infections because of underdeveloped immune system as compared to adults. Strengthening the immune system is a natural way to help the body fight against the disease-causing pathogens and immunomodulators can play a major role in this context. Various Ayurveda classics and studies published in journals related to Ayurveda drugs for improving immunity are reviewed and analysed. In Ayurveda, the objective of immune enhancement is achieved through the use of the Amalakyadi Rasayana (an Immunomodulators), as it increases longevity of life, memory, intellect, luxture, complexion, voice, strength of the body functions, strength of all senses and provides the resistance to disease, improves glow and power. Analysis of classical references and various experimental studies show that Amalakyadi Rasayana posse immuno-modulatory, Antioxidant, Anti-inflammatory, Antimicrobial, Anthelmintic activity. Present paper is a review to update knowledge on pharmacological properties, therapeutic actions and possible mode of action of the selected formulation, Amalakyadi rasayana from Yogaratnakara (Rasayanadhikara/17) to enhance the immunity in children. Rasayana is an important part of Ayurvedic therapeutics used to improve the quality of life by strengthening the tissue quality and by reducing the age-related tissue degeneration. This study reveals that Amalakyadi Rasayana have potential to improve or strengthen the immune system in children and thereby can lower down the morbidity rate in children.
... In a study of bacteria in the mouth due to the properties of antibacterial honey, it proved effective in eliminating germs . It also proved the effectiveness of honey in the treatment of stomach infections in particular and the digestive system in general (Gharzouli et al., 2001;Bilsel et al., 2002;Aysan et al., 2002;Al-waili, 2001). In addition to the fact that honey is vital in the treatment of decay, bacteria that cause bad breath and peptic ulcers, it can be used as an antibiotic in tissue culture and producing a pollution-free medium if used in quantity The experiment aimed at determining the best concentration added to the medium, making the medium free of contaminants and not affecting the process of experiments significantly and proved its ability to rooting (Mehta, 2013) has stimulated honey cutting rooting more than 90% (Federal, 2017) as a natural hormone for rooting and can stimulate the formation of callus in high concentrations and dispense with the use of autoclave because this step expensive because of the cost of the autoclave and what it needs to run, seriousness of the work of this device, To the destruction of many chemical compounds and growth regulators through high temperature and high pressure, which is broken or converted to other compounds not required (Ibrahim, 2017). ...
Article
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In this experiment, honey was tested in the medium used in plant tissue culture as an antibiotic and for the production of a medium resistant to contamination and tested its effectiveness without passing traditional sterilization stages without passing autoclave phase using concentrations (1,2,3,4,6,8) g/L without autoclave and then was incubation with different explants (seeds, shot tip, callus) of castor plan. The results showed that the addition of honey to medium has a significant effect in the conservation medium of contamination without use of autoclave at the concentrations (4, 6, 8) g / L of honey where there was no contamination during the incubation period 20 days and the same concentrations that have not contaminated after incubation of the explants. While the autoclaved medium did not contaminate at all the honey concentrations, the high concentrations effected in direction explants growth and tissues in the concentrations (6, 8) g / L failed in seed germination, rooting shoot tip growth and stimulated callus growth while concentration did not appear 4g/L impact on the direction of growth in addition to being a medium resistant to contamination.
Chapter
Honey has been used for its nutritional and medicinal values since the Stone Age. Being one of the oldest foods known to humans, honey as a natural product has become an important part of food, economy and health care for most of the population. Honey stands as the most vastly discussed natural product across religions and civilizations. Traditional knowledge of these natural products has served as the base for many breakthrough discoveries, especially in the medicinal field. Today honey holds a strong position among its natural counterparts in terms of global market. This chapter provides an in-depth review of historical evidences of honey in different civilizations, religions and cultures, its use as an ethnomedicine, its application in different traditional system of medicine like Unani and Ayurveda, its physico-chemical properties, its modern application as antioxidant, antimicrobial, wound healing and antiviral agent, its application in ophthalmology, cough, diabetes and inflammation, intellectual properties and patent insights on honey, and industry and marketing insights of honey.
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Natural honey (NH) is a highly nutritious substance and is considered as one of nature’s wonders which has been used by all cultures, traditions and civilizations as a food and medicine. Natural honey (NH) is a by-product made by honeybees by using nectar of flowers and sugary non-floral deposits obtained from plants that is then converted into honey by a process of regurgitation and evaporation. Later the honeybees store honey as a primary source of food in wax honeycombs inside the beehive. Honey is classified on the basis of processing, physical, chemical, and nutritional properties. Honey also plays a part in symbolism and religion. The appearance, quality, sensory perception, and composition of NH vary greatly depending on the nectar source, environmental and climatic conditions. Honey’s main constituents include carbohydrates, primarily fructose and glucose although it also contains various oligosaccharide sugars. Besides these NH, also contains minute quantities of amino acids, proteins, enzymes, trace elements, minerals, vitamins, aroma substances, and polyphenols. NH shows a vast range of health and nutritional properties. NH imparts antimicrobial, anti-inflammatory, antioxidant, immune boosting property, antiviral, antiparasitory, antimutagenic, and antitumor effects. Honey has also been well known for treatment of gastrointestinal disorders like peptic ulcers, gastroenteritis, and gastritis. Thus NH has proved a valuable nutritional food and medicinal entity.
Chapter
Fibrosis is a consequence of diverse continual compensation of various connective tissue in the body. That results in the formation of extracellular matrix that is why it forms a sandwiched between matrix and deterioration. It is well resolute and articulated as scarring and as of particular cell lines fibrosis is developed, such conditions are known as a fibroma. Immune cells produce several factors like cytokines, chemokines, etc. that serves as the best factors which affects the inflammation. A variety of synthetic and herbal drugs are accessible in the market that are specially designed for the treatment of fibrosis. Throughout the remedies, honey is one of the most common and easily available ingredient of our kitchen that contains numerous enzymes, vitamins, organic acids, flavonoids, phenolic acids, amino acids, and volatile components. These phytochemicals are responsible for different pharmacological activities including anti-fibrotic effect. In this chapter, we focused on mechanisms of the anti-fibrotic effects of honey and we conclude that how honey inhibits the inflammatory cytokines, chemokines, and other factors viz. PDGF, IL-4, TGF-β, and interleukin-13. These biomarkers are incorporated with proliferation and causes activation of myofibroblast cells. Balance for the extracellular matrix degradation and its synthesis helps determine ECM homeostasis. At last, these immune cells, endothelial or epithelial cells lead to apoptosis, proliferation, and repair at the damage site, resulting in the healing of the wound and showed a strong anti-fibrotic effect.
Article
Honey is one of the most appreciated and valued natural products introduced to humankind since ancient times. Honey is used not only as a nutritional product but also in health described in traditional medicine and as an alternative treatment for clinical conditions ranging from wound healing to cancer treatment. The aim of this review is to emphasize the ability of honey and its multitude in medicinal aspects. Traditionally, honey is used in the treatment of eye diseases, bronchial asthma, throat infections, tuberculosis, thirst, hiccups, fatigue, dizziness, hepatitis, constipation, worm infestation, piles, eczema, healing of ulcers, and wounds and used as a nutritious supplement. The ingredients of honey have been reported to exert antioxidant, antimicrobial, anti-inflammatory, antiproliferative, anticancer, and antimetastatic effects. Many evidences suggest the use of honey in the control and treatment of wounds, diabetes mellitus, cancer, asthma, and also cardiovascular, neurological, and gastrointestinal diseases. Honey has a potential therapeutic role in the treatment of disease by phytochemical, anti-inflammatory, antimicrobial, and antioxidant properties. Flavonoids and polyphenols, which act as antioxidants, are two main bioactive molecules present in honey. According to modern scientific literature, honey may be useful and has protective effects for the treatment of various disease conditions such as diabetes mellitus, respiratory, gastrointestinal, cardiovascular, and nervous systems, even it is useful in cancer treatment because many types of antioxidant are present in honey. In conclusion, honey could be considered as a natural therapeutic agent for various medicinal purposes. Sufficient evidence exists recommending the use of honey in the management of disease conditions. Based on these facts, the use of honey in clinical wards is highly recommended. Summary: There are several evidence that suggesting the usage of honey in the management of disease. Therefore, honey in clinical wards is highly recommended. Abbreviations Used: WA: Water activity, RDI: Recommended daily intake, Si: Silicon, RB: Rubidium, V: Vanadium, Zr: Zirconium, Li: Lithium, Sr: Strontium, Pb: Lead, Cd: Cadmium, As: Arsenic, MIC: Minimum inhibitory concentration, PARP: Poly (ADP-ribose) polymerase, ROS: Reactive oxygen species, iNOS: Inducible nitric oxide synthase, NKcells: Natural killer cells, SCFA: Short-chain fatty acid, CRP: C-reactive protein.
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Throughout time, honey proved to meet all the criteria for its usage as a topical treatment in wounds, due to its antibacterial, anti-inflammatory and antioxidant properties.A major importance was attributed to the compounds found in honey, such as glucose oxidase, methylglyoxal, low pH and hydrogen peroxide. The aim of this review is to provide an updated scientific support regarding the current state and the perspectives on honey application in the veterinary medical therapeutics. We sustain the utility of this documentation because of the contradiction between the abundance of research in the human medicine field and their sporadic character in the medical veterinary one. We assess that honey should not be simply considered as a ‘folk remedy’, but as a modern therapy. Moreover, this review intends to inform the veterinary clinicians about the therapeutic potential of honey, exerted especially on wounds healing and regenerative therapy.
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Dysregulation of joint tissue homeostasis induces articular degenerative changes and musculoskeletal diseases such as osteoarthritis. This pathology represents the first cause of motor disability in individuals over 60 years of age, impacting their quality of life and the costs of health systems. Nowadays, pharmacological treatments for cartilage disease have failed to achieve full tissue regeneration, resulting in a functional loss of the joint; therefore, joint arthroplasty is the gold standard procedure to cure this pathology in severe cases of Osteoarthritis. A different treatment is the use of anti-inflammatory drugs which mitigate pain and inflammation in some degree, but without significant inhibition of disease progression. In this sense, new therapeutic alternatives based on natural compounds have been proposed to delay osteoarthritis progression, particularly those agents that regulate articular homeostasis. Preclinical studies have shown a therapeutic application of honey and its bioactive compounds, ranging from treating wounds, coughs, skin infections, and are also used as a biological stimulant by exerting antioxidant and anti-inflammatory properties. In this article, we reviewed the current medicinal applications of honey with particular emphasis on its use regulating articular homeostasis by inhibiting inflammation and oxidative stress.
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Understanding honey as an agent for wound healing is one area of study that needs more studies in recent times. Wound refers to the breakage of the intactness of skin epidermis, which can either be superficial or deep. Wound healing happens by an array of mutual molecular processes that function in synergy to re-establish the wholeness of tissues and the functions of cells. There are different mechanisms of wound healing methods which include: stimulating cytokine synthesis, hyper osmosis, synthesis of transforming growth factor-β1 among others. Globally, honey is a well-known sweetener and a popular product that is used at homes which is non-toxic, non-irritant, cheap and readily available in different countries. It plays role in the healing of wounds for decades, but its efficacy was not known until recent times when scientific evidence becomes available. Honey has been used to target myriad of wound types to inhibit microorganisms, reduce pain and malodour, and necessary debridement. Its acidity content and high osmolarity caused it to be less favourable for protease activity and beneficial to the healing process of wounds. Honey possesses a myriad of biological activities, which encourage the immune response, prevent inflammation, and also enhances removal of dead tissues by enzymes to accelerate the wound healing processes. Scientific reports from research that involve animals and clinical trials have found that honey could enhance the wound’s healing process. Applying honey on wounds gives a quick healing outcome by processes that include: stimulation of healing process, cleansing actions of wounds, infection clearance, stimulating the regulation of tissues, reducing inflammation, and non-adhesive tissue arrangement. Although, its usage in preventing radiation mucositis and minor burns are places that honey indicates promises of healing. This chapter aims to summarize honey as a potential wound healing agent.
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This review paper aims to explain the morphology, nutritional benefits, ethnomedicinal, pharmacological actions, and therapeutic uses of Asl (Honey). Thus, it will provide significant opportunities for future research to explore its Nutraceutical potential and develop better medicine for Eczema, Diaper Dermatitis, Psoriasis, and Burn. We reviewed the published literature on Asl (Honey) using bibliographic databases such as PubMed, Google Scholar, Science Direct, and web of science, and Unani Classical literature books such as Ibn Baitr, Al Jamai-ul-Mufradt al Advia wal Aghzia, Najmulghani AH. Khazain-ul-advia, Ibn Rushd kitab ul kulliya, Ibn Rushd kitab ul kulliya, Ibn Rushd kitab ul kulliya, Ibn Rushd kitab ul kulliya, Ibn Rushd Since ancient times, t. Asl (Honey) has been administered as an appetizer, aphrodisiac, cicatrizant, anthelmintic, anti-inflammatory, analgesic, Nutrient, deobstruent, lithotriptic, tonic for the stomach, and antiseptic, most often by practitioners of traditional Unani medicine. Asl and its formulations, according to Unani medicine, can help treat Eczema, Diaper Dermatitis, Psoriasis, Burn, and other skin disorders. Some clinical research also highlights the possibility of such an effect, e.g., Honey is a natural anti-angiogenic and anti-inflammatory agent, corneal scratching caused by surgery and exotoxin-induced inflammation of the cornea when applied topically. Albeit more detailed study is necessary to back up these sayings.
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Honey is both a complex food and medicine as well as a healthy alternative to refined sugar. Besides a complex mixture of carbohydrates, honey contains other minor substances which may threaten human health in excess concentrations. Several environmental conditions can affect the quality of honey. This research paper aims to measure the degree of heavy metals (Lead (Pb), Cadmium (Cd), Zinc (Zn), and Copper (Cu)) in some polyfloral honey from an industrial area of Romania, considered to be one of the most polluted regions in Eastern Europe. The samples were collected from six stationary apiaries and analysed using the atomic absorption spectrometry method. The content of Pb was higher in the sampling areas exposed directly to the polluted air masses. Cd concentration decreases exponentially while Cu concentration increases as the distance from the source of pollution increases. The checking of the quality of polyfloral honey from local producers is imperative because this product is intended to be consumed by the beekeeper’s family or the local community without being sold to an authorised processor. The results of the study can help to set a threshold for the concentration of Pb and Cd in honey marketed in the European Union.
Chapter
Honey is one of the most nutritional natural products that not only provides us healthy nutrition but also has a potential to be an alternative treatment option for different pathologies from microbial infection to metabolic disease. Honey is a byproduct of flower syrup produced by honeybees and possesses an intricate chemical composition that varies with botanical sources and geographical locations. This chapter is aimed to provide readers an understanding of complex composition, biological activities, adverse effect, and therapeutic benefits of honey. Honey possesses many biological activities, such as antioxidant, anti-microbial, anti-inflammatory, anti-proliferative, anti-cancer, and anti-metastatic effects, suggesting potential therapeutic roles in many human pathologies. Flavonoids and polyphenols in honey are the two active ingredients, which are of therapeutic importance in many diseases. In conclusion, honey may be developed as a natural therapeutic agent for many pathologies, and extensive studies are therefore recommended.
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The possibility that the mode of action of sulphasalazine and its active metabolite 5-amino-salicylic acid (5ASA) involves modification of toxic oxygen metabolite production by neutrophils has been investigated by measuring the effect of these drugs on luminol-dependent chemiluminescence, superoxide release and oxygen consumption by stimulated neutrophils in vitro. 5ASA, and to a lesser extent sulphasalazine, had profound inhibitory effects on the luminol dependent chemiluminescent response of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (1 microM) + cytochalasin B (5 micrograms/ml). A concentration of 50 microM 5ASA or sulphasalazine produced 93.8 (2.3)% and 65.7 (3.7)% inhibition of control responses respectively. The concentration of 5ASA and sulphasalazine producing 50% inhibition of chemiluminescence were 3.6 (1.8) microM and 16.5 (6) microM respectively. Both drugs had little effect on the chemiluminescent response of neutrophils stimulated with phorbol myristate acetate (1 microgram/ml), producing only 11.4 (3.9)% and 34 (7)% inhibition respectively, at a concentration of 50 microM. Superoxide release from fMLP + CB stimulated neutrophils was also inhibited slightly by 5ASA (50 microM) by 35.6% and by sulphasalazine (50 microM) by 7.9%. Similarly, there was little inhibition in the rate of oxygen consumption by fMLP + CB stimulated neutrophils by either 5ASA or sulphasalazine at concentrations which produced near total abolition of luminol dependent chemiluminescence. These results show that sulphasalazine and 5ASA inhibit the reaction of toxic metabolites produced by stimulated neutrophils with luminol, without inhibition of the oxidase system producing these metabolites. The site of action of these drugs on neutrophils in vitro is thus extracellular, by scavenging a released metabolite, probably hypochlorite. This has important implications for their mode of action in vivo in inflammatory bowel disease.
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In our study we have tried to compare the prophylactic effects of superoxide dismutase (SOD), SOD+catalase (CAT), desferrioxamine, verapamil and disulfiram, which are all free oxygen radical (FOR) scavengers, in an animal model of experimental acetic acid colitis. The control group had 58.3% colonic ulcers. The SOD group (48.6% ulcerated area) and the SOD+CAT group (47.2% ulcerated area) did not show a significant difference when compared with the control group. The values were significantly different in all other groups when compared with the control group (desferrioxamine (29.2% ulcerated area): P < 0.01; verapamil (10.4% ulcerated area) and disulfiram (7.6% ulcerated area): P < 0.001. In conclusion, desferrioxamine, verapamil and disulfiram have been found to be effective as prophylactics in experimental acetic acid colitis.
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Hypothesis Tumor implantation (TI) development at the surgical wound following cancer surgery is still an unresolved concern. Trocar site recurrence, which is likely a form of TI, has become one of the most controversial topics and, with the widespread acceptance of laparoscopic surgery, has caused renewed interest in questions about TI. Honey has positive effects on wound healing. Physiological and chemical properties of honey might prevent TI when applied locally.Design, Interventions, and Main Outcome Measures Sixty BALB/c strain mice, divided into 2 groups, were wounded in the posterior neck area. Group 1 mice formed the control group, and group 2 mice had wounds coated with honey before and after tumor inoculation. All wounds were inoculated with transplantable Ehrlich ascites tumor. The presence of TI was confirmed in the wounded area by histopathological examination on the 10th day.Results Tumor implantation was achieved in all group 1 animals and verified by palpable mass and histopathological examination. In group 2 mice, although TI could not be detected macroscopically, it was revealed by pathological examination in 8 cases. Tumor implantation was less likely in group 2 mice (8 of 30 vs 30 of 30; P<.001).Conclusions Tumor implantation was markedly decreased by the application of honey pre- and postoperatively. It is possible that the physiological and chemical properties of honey protected wounds against TI. Honey could be used as a wound barrier against TI during pneumoperitoneum in laparoscopic oncological surgery and in other fields of oncological surgery.
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Increases in nitric oxide synthase (NOS) activity 4 h after endotoxin (3 mg kg–1 i.v.) were greater in colonic mucosa than in muscle and were calcium-independent in mucosa but calcium-dependent in the muscle. Induction of NOS in both tissues was prevented by dexamethasone (1 mg kg–1 s.c.). Hence, these increases in NOS activity may represent distinct inducible NOS isoforms. In colitis produced by intracolonic trinitrobenzene sulphonic acid, initial colonic damage was accompanied by induction of calcium-independent NOS. In contrast, the later colonic healing was accompanied by an increase in calcium-dependent NOS activity, which may represent constitutive NOS activity associated with tissue regeneration. Excessive NO production by inducible NOS in the colonic mucosa after LPS and in colitis is likely to play an important role in the vascular damage, whilst increased synthesis of NO in colonic muscle may produce motility changes.
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The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.
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Ulcerative colitis and Crohn's disease are complex, problematic diseases of unknown etiology in man, and appropriate experimental models would be useful in elucidating their pathogenesis and treatment. Although there have been numerous attempts to produce inflammatory ulcerative colonic disease in laboratory animals resembling those human disease forms, none has been entirely successful. Investigators have conducted experiments involving almost every etiological factor suggested for initiation of these diseases. The methods reviewed in this paper include production of experimental colitis by vascular impairment, and immunological methods such as bacterial infection, allergic reactions, direct and indirect hypersensitivity reactions, as well as autoimmune mechanisms. The results of carrageenan-induced colitis, irradiation, dietary, and drug-induced techniques are also discussed and the frequency and nature of spontaneous colonic lesions in animals is summarized.
Article
Colitis was induced in rats by intrarectal administration of trinitrobenzene sulfonic acid (80 mg/kg, in 30% ethanol). An acute inflammation with ulcers and neutrophil infiltration developed that evolved into a chronic inflammation and luminal narrowing with attendant smooth muscle hypertrophy. We assessed the effects of 16,16-dimethyl prostaglandin E2, administered either before or after trinitrobenzene sulfonic acid, on the development of inflammation. Inflammation was assessed by gross appearance using a grading scale (0-4) and by histology. The number of neutrophils present in inflamed colonic tissue was quantitated by the myeloperoxidase assay. The production of lipoxygenase products was monitored by incubation of colonic specimens with [14C]arachidonic acid and separation of the products by thin-layer chromatography and high-pressure liquid chromatography. Levels of leukotriene B4 were measured in tissue extracts by high-pressure liquid chromatography and ultraviolet absorbance. Eicosanoid production was also assayed by incubating colonic specimens and assaying the media for prostaglandin E2, leukotriene B4, and leukotriene C4 by radioimmunoassay. Trinitrobenzene sulfonic acid treatment resulted in a greatly increased amount of leukotriene B4 in the media. Treatment with 16,16-dimethyl prostaglandin E2 before administration of trinitrobenzene sulfonic acid resulted in a lower inflammation index, lower myeloperoxidase activity, and decreased production of leukotriene B4. Administration of 16,16-dimethyl prostaglandin E2 24 h after administration of trinitrobenzene sulfonic acid was also effective in reducing the inflammatory response. Treatment with 16,16-dimethyl prostaglandin E2 also prevented the development of long-term architectural changes 3 wk after administration of trinitrobenzene sulfonic acid. Rectal administration of dimethyl prostaglandin E2 also diminished the colitis induced by direct injection of trinitrobenzene sulfonic acid into the colonic wall.
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Stimulated rat peritoneal neutrophils release a platelet inhibitory factor with the pharmacological properties of NO. This release is inhibited by NG-monomethyl-L-arginine and L-canavanine, indicating that it occurs through a mechanism similar to that in vascular endothelial cells and macrophages. As the degree of stimulation increases, the factor released is progressively inactivated by concomitant release of superoxide anions.
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Sulphasalazine (Salazopyrin) and its metabolites sulphapyridine and 5-aminosalicylate are powerful scavengers of the hydroxyl radical, determined by pulse radiolysis and confirmed by assays based on deoxyribose degradation by hydroxyl radicals. 5-Aminosalicylate can also protect alpha 1-antiprotease against attack by the myeloperoxidase-derived oxidant hypochlorous acid. The ability to scavenge oxidants produced at sites of inflammation may contribute to the anti-inflammatory action of sulphasalazine and its metabolites.
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Reflectance spectrophotometry measures indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2). In the rat colon, characteristic patterns of IHB and ISO2 are associated with ischemia with congestion (increased IHB and decreased ISO2) and ischemia without congestion (decreased IHB and decreased ISO2). Endoscopic measurements with acceptable interobserver variability was demonstrated in the canine stomach. In eight healthy subjects, endoscopic measurement in different areas of the colon and rectum revealed significantly lower IHB values in the splenic flexure. These observations are compatible with reduced flow and increased susceptibility to ischemic damage in this watershed area. The endoscopic measurements in 13 patients with active inflammatory bowel disease revealed an increase in IHB and ISO2 values in the involved areas, indicating an increase in mucosal blood flow. In six patients restudied when the disease remitted, these values returned to normal.
Article
Our previous studies had suggested a link between bile salt stimulation of colonic epithelial proliferation and the release and oxygenation of arachidonate via the lipoxygenase pathway. In the present study, we examined the role of reactive oxygen versus end products of arachidonate metabolism via the cyclooxygenase and lipoxygenase pathways in bile salt stimulation of rat colonic epithelial proliferation. Intracolonic instillation of 5 mM deoxycholate increased mucosal ornithine decarboxylase activity and [3H]thymidine incorporation into DNA. Responses to deoxycholate were abolished by the superoxide dismutase mimetic CuII (3,5 diisopropylsalicylic acid)2 (CuDIPS), and by phenidone or esculetin, which inhibit both lipoxygenase and cyclooxygenase activities. By contrast, indomethacin potentiated the response. Phenidone and esculetin suppressed deoxycholate-induced increases in prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5, 12, and 15-hydroxyeicosatetraenoic acid (HETE), whereas CuDIPS had no effect. Indomethacin suppressed only PGE2. Deoxycholate (0.5-5 mM) increased superoxide dismutase sensitive chemiluminescence 2-10-fold and stimulated superoxide production as measured by cytochrome c reduction in colonic mucosal scrapings or crypt epithelium. Bile salt-induced increases in chemiluminescence were abolished by CuDIPS, phenidone, and esculetin, but not by indomethacin. Intracolonic generation of reactive oxygen by xanthine-xanthine oxidase increased colonic mucosal ornithine decarboxylase activity and [3H]thymidine incorporation into DNA approximately twofold. These effects were abolished by superoxide dismutase. The findings support a key role for reactive oxygen, rather than more distal products of either the lipoxygenase or cyclooxygenase pathways, in the stimulation of colonic mucosal proliferation by bile salts.
Article
An assay was devised to quantitate acute intestinal inflammation based on the assessment of myeloperoxidase activity. Myeloperoxidase is an enzyme found in neutrophils and, in much smaller quantities, in monocytes and macrophages. Myeloperoxidase was solubilized with hexadecyltrimethylammonium bromide and myeloperoxidase activity was measured with a dianisidine-H2O2 assay. In neutrophil suspensions, myeloperoxidase activity was directly related to cell number down to as few as 500 cells. Myeloperoxidase activity was assayed in two animal models of inflammation: acetic acid-induced colitis in rats and Clostridium difficile enterotoxin-induced enteritis in hamsters. In both models, the activity of myeloperoxidase solubilized from the inflamed tissue was directly proportional to the number of neutrophils seen in histologic sections. Histologic evaluation of neutrophil accumulation was performed by counting the number of neutrophils in a histologic section 0.18 mm long and 5 micron thick. In both animal models, myeloperoxidase activity was linearly related to neutrophil number from 400 and 4000 cells/mm. Myeloperoxidase activity from chronically inflamed colon, in which both neutrophils and histiocytes were present, was directly related to neutrophil content. Histiocytes did not contribute significantly to myeloperoxidase activity. The determination of myeloperoxidase activity in the intestine is a simple biochemical assay that can be used to quantitate inflammation.
Article
Leukotriene B4, an arachidonic acid metabolite, is a potent chemotactic agent, and is thought to be an important mediator of inflammation. To investigate the role of this compound as a mediator of inflammation in inflammatory bowel disease, arachidonic acid was incubated with ionophore and colonic mucosa from patients with inflammatory bowel disease and from normal subjects. Mucosa from patients with inflammatory bowel disease converted 2.17% of exogenous arachidonate to leukotriene B4; mucosa from normal subjects converted 0.37%. The production of leukotriene was blocked by sulfasalazine. To determine if inflammatory bowel mucosa contained endogenous leukotriene B4, lipid extracts were analyzed by high pressure liquid chromatography. Mucosa from patients with inflammatory bowel disease contained 254 ng of leukotriene B4 per gram and mucosa from normal subjects contained less than 5 ng of leukotriene B4 per gram. The presence of significant amounts of leukotriene B4 in colonic mucosa in patients with inflammatory bowel disease, combined with the known biologic effects of leukotriene B4, suggests that it may be an important mediator of inflammation in inflammatory bowel disease.
Article
Evidence is presented that supports a role of oxygen free radicals in the pathogenesis of various disorders of the digestive system. In the intestine, there is evidence that oxygen radicals play an important role in the endothelial and epithelial damage associated with certain models of ischemia. The mechanism for superoxide production in this condition differs from that described for other pathologic states (i.e., oxygen toxicity and neutrophil-mediated inflammation). This mechanism involves the reaction of xanthine oxidase, hypoxanthine, and molecular oxygen to produce a burst of oxygen radicals with reperfusion of the ischemic bowel. Evidence implicating oxygen radicals in inflammatory disorders of the digestive tract (i.e., pancreatitis), radiation injury, and hepatic cirrhosis is also presented. The available data suggest that oxygen radicals appear to be a fundamental mechanism of tissue injury in the pathogenesis of various disorders of the digestive system.
Article
A method for the estimation of nitrate and nitrite is described in which nitrate is converted to nitrite by Klebsiella pneumoniae (UNF 9232) and nitrite is estimated by the Griess reaction before and after incubation. The method is suitable for the estimation of 1-25 nmol of each ion in body fluids, many samples can be handled simultaneously, and special apparatus is not required.
Article
Excessive nitric oxide (NO) production by an isoform of NO synthase that can be induced by inflammatory stimuli leads to changes in vascular permeability and to tissue injury. We measured NO synthase activities in mucosa and muscle from the colons of control patients (n = 11) and patients with ulcerative colitis (6) or Crohn's disease (4). NO synthase activity in colonic mucosa of ulcerative colitis patients was 0.55 (median interquartile range 0.32-0.57) nmol/min per g tissue, which was about eightfold higher than the value in control mucosa, with no individual overlap (p < 0.001). With colonic muscle there was no difference in NO synthase activity between ulcerative colitis patients and controls. In the patients with Crohn's disease, mucosal NO synthase activity did not differ from control values and activity in the colonic muscle was low. Thus, induction of colonic NO synthase may be involved in the mucosal vasodilation and increased vascular permeability of active ulcerative colitis, and could also contribute to the impaired motility that accompanies toxic dilation.
Article
A prospective randomized clinical study to compare honey-impregnated gauze with amniotic membrane dressing in partial thickness burns was carried out. Sixty-four patients were studied. Forty of them were treated with honey-impregnated gauze and 24 were treated with amniotic membrane. The burns treated with honey healed earlier as compared to the amniotic membrane (mean 9.4 vs 17.5 days) (P < 0.001). Residual scars were noted in 8 per cent of patients treated with honey-impregnated gauze and in 16.6 per cent of cases treated with amniotic membrane (P < 0.001).
Article
Nitric oxide (NO) is produced in tissues by NO synthase with the liberation of equimolar amounts of citrulline. Citrulline concentrations were significantly higher in rectal biopsy specimens from patients with active ulcerative colitis than in those from patients with quiescent disease or with normal histology. Incubation of biopsy samples from patients with ulcerative colitis with NG-monomethyl-L-arginine (L-NMMA) inhibited citrulline production. These findings suggest that mucosal NO biosynthesis is increased in active colitis and that NO may have a pathogenic role in ulcerative colitis.
Article
Much of the lung damage that limits the life of young adults with cystic fibrosis is due to proteases and oxygen metabolites generated by neutrophils, which are recruited into the airway by the interaction between Pseudomonas aeruginosa and pulmonary macrophages. Leukotriene B4 (LTB4) has been proposed as a local mediator of this process; its production is susceptible to specific modulation with dietary eicosapentaenoic acid (EPA). We carried out a placebo-controlled trial of EPA (2.7 g daily for 6 weeks) to assess its effects on markers of clinical state, peripheral neutrophil function, and lung inflammation in sixteen patients with cystic fibrosis colonised with P aeruginosa. EPA was well tolerated and resulted in a significant reduction in sputum volume (median change with EPA -10 mL/day, placebo 0; p = 0.015), and improvements in Schwachman score (EPA 5%, placebo 0; p = 0.034), forced expiratory volume in 1 s (EPA 0.25 L, placebo -0.1 L; p = 0.006), and vital capacity (EPA 0.6 L, placebo 0; p = 0.011). Relative chemotaxis of circulating neutrophils to LTB4 increased from a subnormal baseline of 4 (median; range 0-10) microns/30 min before treatment, to a near normal value of 11 (5-18) microns/30 min after EPA. Relative chemotaxis to LTB4 of patients taking placebo did not change: the difference in response was highly significant (p = 0.001). Specific reduction of neutrophil chemotaxis to LTB4 is a sensitive assay of chronic in-vivo exposure to LTB4. Our results suggest that LTB4 has a pathogenetic role in the lung damage of cystic fibrosis. Longer-term clinical trials of EPA are warranted in a larger number of cystic fibrosis patients.
Article
Since a long time, honey has been used in wounds and skin ulcer treatment. Nowadays, it's healing properties are again being discovered. Its good application on wounds and infected burns gives satisfactory results. This work is a study done on 40 patients with wounds of various origin. Honey has healed 88 per cent of the cases. Some germs have been found on the wound at the end of the cicatrization but have not blocked the healing process. This simple, efficient, cheap and with no side effects treatment deserves being better known and integrated in the set of common antiseptics.
Article
Nitric oxide (NO) synthesis is increased in ulcerative colitis, but the role of NO in colitis is poorly understood. The present study employed NW-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in rats to evaluate the effect of NO on 2,4,6-trinitrobenzenesulphonic acid (TNB)-induced colitis. L-NAME solutions were placed in subcutaneous, osmotic mini-pumps which continuously released L-NAME at 0.042, 0.208, 0.417, or 1.667mgkg−1 h−1. L-NAME dose-dependently enhanced lesions in TNB-induced colitis. The two higher doses of L-NAME significantly increased colonic mucosal damage, although there was slight, nonsignificant reduced lesion formation with the lowest dose of L-NAME, 0.042 mgkg−1 h−1. A single dose of L-NAME at 100 mgkg−1 subcutaneously injected daily in TNB-treated rats also increased lesions, and these ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine (both at 500mgkg−1, s.c). Only the highest dose of L-NAME (mini-pump) significantly depressed myeloperoxidase (MPO) activity. Faecal occult bleeding showed a close relationship with severity of colitis. These findings suggest that there may exist a balance between NO protective and aggressive effects. In TNB-induced colitis, antagonism of endogenous NO generation was intensified, whereas slight inhibition of NO synthesis reduced lesions. Variations in responses, related to timing or dose changes in L-NAME, may reflect the differences in inducible vs constitutive NO synthase isoforms.
Article
Keratinocyte growth factor (KGF) is known to enhance tissue repair in the skin; however, its role in the gastrointestinal tract is largely unknown. The aim of this study was to evaluate the effects of exogenous KGF in an experimental model of colitis in rats. KGF was administered before or after induction of colitis with 2,4,6-trinitrobenzenesulfonic acid/ethanol. In the first two study groups, KGF (5 mg/kg) was administered intraperitoneally 24 hours and 1 hour before induction of colitis; animals were killed 8 hours (n=10) and 1 week (n=10) after injury. In subsequent study groups, KGF or vehicle treatment was begun 24 hours after the induction of colitis at doses of 5 (n=20), 1 (n=10), and 0.1 (n=10) mg/kg intraperitoneally and continued once daily for 1 week. Colonic tissue samples were evaluated macroscopically and microscopically for mucosal injury and assayed for myeloperoxidase activity. Administration of KGF after but not before induction of colitis significantly ameliorated tissue damage. Macroscopic necrosis and microscopic ulcerations were reduced by 40%-50% at KGF doses of 1 and 5 mg/kg. Exogenous KGF has a key role in mucosal healing in an experimental model of colitis in rats.
Article
Honey from New Zealand and Saudi Arabia at concentrations approximating 20% (v/v) inhibit the growth of H. pylori in vitro. The anti-H. pylori effect involves both hydrogen peroxide- and non-peroxide-mediated killing mechanisms. This study was designed to determine whether the anti-H. pylori activity of honey differed regionally (honey from Texas, Iowa, and New Zealand) and to determine whether this activity was due to the presence of hydrogen peroxide. Broth dilution susceptibility tests were performed using solutions of honey prepared in BHI broth ranging in concentration from 5 to 35% (v/v) in 5% increments. Control solutions containing glucose, fructose, and combined glucose/fructose solutions in ratios of 1:1.23 were also prepared. Paired catalase controls were included in all tests. Twenty-eight clinical isolates of H. pylori were tested. Growth was determined on the basis of a plus/minus grading score. All of the solutions containing either fructose, glucose, glucose and fructose combinations, or honey were equally effective in inhibiting the growth of H. pylori. All of the isolates were inhibited by solutions containing 15% (w/v) carbohydrate. Honey solutions, with or without catalase, inhibited 24/28 isolates at a concentration of 10%, and 28/28 isolates at a concentration of 15%. In conclusion, regional differences in honey activity against H. pylori were not detected, nor was the effect of killing related to the presence of hydrogen peroxide in the honey samples. Osmotic effects were shown to be the most important parameter for killing H. pylori as all carbohydrate solutions > or = 15% (v/v) inhibited 100% of the H. pylori.
Article
Increased concentrations of nitrate and nitrite (the breakdown products of nitric oxide) in the serum and faeces of patients with inflammatory bowel disease (IBD) suggests that increased synthesis of nitric oxide occurs in IBD. The aim of this study was to assess aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase, with regard to its effectiveness as a nitric oxide inhibitor and as a modulator of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Colitis was induced in Wistar rats. Selective (AMG) and non-selective (1-nitroso-arginine methyl ester (1-NAME)) inhibitors of nitric oxide synthase were given in the drinking water. Colonic citrulline and arginine concentrations were assessed using high-performance liquid chromatography. The severity of colitis was assessed by a macroscopic scoring system. Both 1-NAME and AMG successfully reduced nitric oxide synthesis. There was no evidence of substrate depletion in the colonic wall. Neither of the agents reduced the severity of colonic inflammation. Oral administration of nitric oxide synthase inhibitors reduced nitric oxide synthesis in the colonic wall. This study does not provide evidence to support a role for nitric oxide in the pathogenesis of colonic inflammation in TNBS colitis.
Article
It has been proposed that oxidative stress is involved in the pathophysiology of ulcerative colitis. We have reported the depletion of the nonenzymatic antioxidant, glutathione, in colon from active and inactive ulcerative colitis. The colon contains several biochemically linked antioxidant systems. We hypothesized that diminished total antioxidant capacity in active ulcerative colitis would be associated with increased colonic lipid peroxidation. This study was designed to determine total antioxidant capacity and lipid hydroperoxide levels using colon obtained at surgery from controls (N = 16; 4 females, 12 males; mean age 70 years), and active and inactive ulcerative colitis (N = 15; 3 females, 12 males; mean age 39). Total antioxidant capacity of control colon was higher in muscularis externa compared to the mucosal-submucosal layer (P < 0.05). There were no differences in colonic total antioxidant capacity or lipid hydroperoxide levels comparing control colon to inactive and active ulcerative colitis. The results did not support depletion of tissue total antioxidant capacity by free radicals. Depletion of glutathione in ulcerative colitis may be a specific disorder rather than a secondary defect attributable to global oxidative stress. Nonspecific antioxidant supplements appear unlikely to be beneficial in the treatment of ulcerative colitis.