Chemical composition and antioxidant content of Thymus vulgaris honey and Origanum vulgare essential oil; their effect on carbon tetrachloride-induced toxicity.

AIM: The study investigated the chemical composition, antioxidant content, and antioxidant activity of Thymus vulgaris honey (TVH) and Origanum vulgare essential oil (OVEO) and their mixture effect on carbon tetrachloride (CCl4)-induced toxicity. MATERIALS AND METHODS: The study conducted physicochemical characterization and chemical analysis of TVH and OVEO with the use of gas chromatography-mass spectrometry and high-performance liquid chromatograph (HPLC). The antioxidant activity of TVH and OVEO was done with the use of 1,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The study used nine groups of rats to investigate the effect of TVH, OVEO, and a mixture of TVH and OVEO (HEM) on CCl4-induced toxicity. Intraperitoneal injection of CCl4 (1 mL/100 g) was used to induce toxicity. The doses of TVH and OVEO were 1 mg/kg.b.wt, and 50 mg/kg.b.wt, respectively. HEM contains TVH (1 mg/kg.b.wt) and OVEO (50 mg/kg.b.wt). RESULTS: TVH has a high content of phenols, flavonoids, and flavanols. HPLC analysis showed that TVH contains, for the 1st time, epicatechin gallate, and at a high concentration. OVEO includes a high percentage of carvacrol and thymol. With the use of DPPH, OVEO was more potent than TVH. CCl4 caused significant liver and kidney damage and lipid disorders, which were alleviated by HVT, OVEO, and HEM. HVT was more potent than OVEO (p<0.05), and HEM was more potent than HVT and OVEO (p<0.05). CONCLUSION: The study identified high content of epicatechin gallate for the 1st time in TVH, and OVEO contains a high percentage of thymol and carvacrol. Epicatechin gallate might be useful as a marker for TVH. Mixing OVEO and TVH significantly potentiated their protection against CCl4-induced liver and kidney toxicity.

Antioxidant activity and protective effect of bee bread (honey and pollen) in aluminum-induced anemia, elevation of inflammatory makers and hepato-renal toxicity.

Aluminum toxicity might be related to oxidative stress, and the antioxidant activity and protective effect of bee bread, which contains pollen, honey and bees' enzymes, on aluminum induced blood and hepato-renal toxicity was investigated in rats. Chemical analysis and antioxidant capacity of bee bread were conducted. The animal experiment in rats included; group 1: received distilled water (10 ml/kg b.wt), group 2: received aluminum chloride (662.2 mg/kg b.wt), group 3: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (500 mg/kg b.wt), and group 4: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (750 mg/kg b.wt). Doses were given once daily via a gavage. C-reactive protein, transaminases, urea, creatinine, creatinine clearance, sodium and potassium and urine sodium and potassium were determined on day 28 of the experiment. Bee bread contained protein, fat, fiber, ash, carbohydrate, phenol and flavonoids and it exhibited antioxidant activity. Aluminum caused a significant elevation of blood urea, transaminase, C-reactive protein and monocyte count and significantly decreased hemoglobin. These changes were significantly ameliorated by the use of bee bread. Bee bread has an antioxidant property, and exhibited a protective effect on aluminum induced blood and hepato-renal toxicity and elevation of inflammatory markers C-reactive protein, leukocyte and monocyte counts.

Antioxidant and diuretic activity of co-administration of Capparis spinosa honey and propolis in comparison to furosemide.

OBJECTIVE: To study the antioxidant properties of Capparis spinosa (C. spinosa) honey and propolis and the effect of combined honey and propolis administration on urine volume and electrolytes in rats. METHODS: C. spinosa honey [1000 mg/kg body weight (b.wt)], propolis (100 mg/kg b.wt), honey/propolis mixture (C. spinosa honey 1000 mg/kg b.wt/ propolis extract 100 mg/kg b.wt ), distilled water (1 mL/kg b.wt) and furosemide (10 mg/kg b.wt) were orally administered to five groups of rats for 21 d. Urine volume, blood and urine sodium, potassium and chloride were measured. The antioxidant activity of propolis and honey was assessed and their total phenols and flavonoids were determined. RESULTS: Propolis and C. spinosa honey contain polyphenols including flavonoids and propolis demonstrated higher antioxidant activities than honey. Honey significantly increased urine volume and urine electrolyte excretion. Propolis had no significant effect on urine volume, but co-administration of propolis and honey caused significant diuresis. No major changes were observed in plasma electrolytes with the use of honey, propolis or their combination. CONCLUSIONS: Honey and propolis have antioxidant activity and contain polyphenols including flavonoids that are more pronounced in propolis. Honey has a significant diuretic activity alone or in combination with propolis. This is the first study comparing the diuretic effect of co-administration of propolis and C. spinosa honey with furosemide.

Comparison of hypotensive, diuretic and renal effects between cladodes of Opuntia ficus-indica and furosemide.

OBJECTIVE: To investigate the diuretic, hypotensive and renal effect of Opuntia ficus-indica in two different species in oral and intravenous administration. METHODS: Diuretic activity was evaluated in rats with the plant cladode gel and aqueous extract administrated orally, and was evaluated in rabbits with plant extract administered intravenously. Single and repeated doses of cladode gel or aqueous extract of cladode were tested. Urine volume and blood and urine creatinine, sodium and potassium were measured, and creatinine clearance was calculated. The hypotensive effect of lyophilized extract of cladode was evaluated in rabbits. Two polyethylene PE50 catheters were used: one in the jugular vein for the infusion of the plant extract and the other in the carotid for the evaluation of the arterial pressure. RESULTS: The cladode gel or aqueous extract increased urine volume, creatinine clearance and urinary excretion of sodium and potassium without significant effect on serum creatinine or blood urea. Furosemide, gel and aqueous extract of cladode insignificantly lowered plasma potassium in rats. Intravenous administration of the lyophilized extract caused a significant decrease in mean arterial pressure in rabbits with a significant increase in urine volume and urine sodium and potassium; the effect was dose dependent. Intravenous administration of lyophilized extract did not affect plasma sodium or potassium. CONCLUSIONS: Gel and aqueous extract of Opuntia ficus-indica cladode have a significant diuretic effect on rats, and the lyophilized extract has a diuretic and hypotensive effect on normotensive rabbits without deterioration in renal function test. Additional studies on active ingredients are essential to pave the way for clinical studies on diuretic and hypotensive effect of the plant.

Natural antioxidants in the treatment and prevention of diabetic nephropathy; a potential approach that warrants clinical trials.

Diabetic nephropathy is the major cause of end-stage renal disease and effective and new therapeutic approaches are needed in diabetic nephropathy and chronic kidney diseases. Oxidative stress and inflammatory process are important factors contributing to kidney damage by increasing production of oxidants. KEAP1/Nrf2/ARE pathway regulates the transcription of many antioxidant genes and modulation of the pathway up regulates antioxidants. NFB controls the expression of genes involved in the inflammatory response. Natural substances have antioxidant and anti-inflammatory activities and have an impact on NFB and KEAP1/Nrf2/ARE pathways. The preclinical studies explored the effectiveness of whole herbs, plants or seeds and their active ingredients in established diabetic nephropathy. They ameliorate oxidative stress induced kidney damage, enhance antioxidant system, and decrease inflammatory process and fibrosis; most likely by activating KEAP1/Nrf2/ARE pathway and by deactivating NFB pathway. Whole natural products contain balanced antioxidants that might work synergistically to induce beneficial therapeutic outcome. In this context, more clinical studies involving whole plants or herbal products or mixtures of different herbs and plants and their active ingredients might change our strategies for the management of diabetic nephropathy. The natural products might be useful as preventive interventions and studies are required in this field.

Honey and cardiovascular risk factors, in normal individuals and in patients with diabetes mellitus or dyslipidemia.

Diabetes mellitus, hypercholesteremia, hypertension (HTN), and obesity are well-known risk factors for cardiovascular diseases (CVD). Various medications are currently in use for management of these comorbidities. Undesirable side effects are unavoidable and the ultimate and ideal goal is hardly achieved. Honey and other bee products are widely used in traditional medicine for management of many diseases. Others and the authors have found potent biological activities of these products. Honey is now reintroduced in modern medicine as part of wound and burn management. Honey has antioxidant, anti-inflammatory, and antimicrobial activities. More studies are exploring other aspects of honey activity such as its effect on blood sugar, body weight, lipid profile, C-reactive protein, nitric oxide, proinflammatory prostaglandins, and homocysteine. Growing evidence and scientific data support the use of honey in patients with diabetes, HTN, dyslipidemia, obesity, and CVD. This review discusses clinical and preclinical studies on potential influence of honey on diabetes mellitus and cardiovascular risk factors, and emphasizes the importance of conducting more clinical and controlled studies.

Ultra-low microcurrent in the management of diabetes mellitus, hypertension and chronic wounds: report of twelve cases and discussion of mechanism of action.

Oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus and cardiovascular diseases including hypertension. The low levels of antioxidants accompanied by raised levels of markers of free radical damage play a major role in delaying wound healing. Ultra-low microcurrent presumably has an antioxidant effect, and it was shown to accelerate wound healing. The purpose of the study is to investigate the efficacy of ultra-low microcurrent delivered by the Electro Pressure Regeneration Therapy (EPRT) device (EPRT Technologies-USA, Simi Valley, CA) in the management of diabetes, hypertension and chronic wounds. The EPRT device is an electrical device that sends a pulsating stream of electrons in a relatively low concentration throughout the body. The device is noninvasive and delivers electrical currents that mimic the endogenous electric energy of the human body. It is a rechargeable battery-operated device that delivers a direct current (maximum of 3 milliAmperes) of one polarity for 11.5 minutes, which then switched to the opposite polarity for another 11.5 minutes. The resulting cycle time is approximately 23min or 0.000732 Hz and delivers a square wave bipolar current with a voltage ranging from 5V up to a maximum of 40 V. The device produces a current range of 3 mA down to 100 nA. Twelve patients with long standing diabetes, hypertension and unhealed wounds were treated with EPRT. The patients were treated approximately for 3.5 h/day/5 days a week. Assessment of ulcer was based on scale used by National Pressure Ulcer Advisory Panel Consensus Development Conference. Patients were followed-up with daily measurement of blood pressure and blood glucose level, and their requirement for medications was recorded. Treatment continued from 2-4 months according to their response. Results showed that diabetes mellitus and hypertension were well controlled after using this device, and their wounds were markedly healed (30-100%). The patients either reduced their medication or completely stopped after the course of treatment. No side effects were reported. The mechanism of action was discussed.

Modulation of prostaglandin activity, part 1: prostaglandin inhibition in the management of nonrheumatologic diseases: immunologic and hematologic aspects.

Prostaglandins (PGs) are active biologic substances that are involved in a wide range of physiologic processes; when their production is out of balance, they are factors in the pathogenesis of illness. Modulation of PGs by inhibition or stimulation is promising for the management of various conditions. PG inhibitors are widely used to relieve pain and inflammation in patients with rheumatologic disease. Interest in the use of PG inhibitors to prevent cancer and cardiovascular events is growing. More than 27 y ago, investigators found that PG depresses antibody production in vivo; reduces serum iron, hemoglobin, and leukoid series in bone marrow during acute and chronic blood loss; reduces albumin during antigenic stimulation; suppresses hypercalcemia after bleeding; and reduces fasting blood sugar and hyperglycemia after ether anesthesia and bleeding. Chronic conditions that produce large quantities of PGs are associated with immunosuppression and secondary anemia. Investigators in the present study hypothesized (1) that the overproduction of PGs is responsible for immunosuppression and secondary anemia in conditions associated with increased PG synthesis, such as pathologic inflammation, malignancy, trauma, and injury, and (2) that PG inhibitors reverse immunosuppression and secondary anemia, thereby enhancing the immune response. This is supported by many reports that show the immunosuppressive effects of PGs and their role in the immunosuppression associated with pathologic inflammation, burns, trauma, and tumors. Inhibition of PGs can be achieved through the use of synthetic medicines and natural products. This article reviews the effects of PGs and inhibition of increased synthesis of PGs on the lymphoid system, hematologic indices, and bone marrow elements in trauma, injury, burns, and tumors. The Medline database (1966-2006) was used in this study. Investigators in the present study and others have provided evidence that shows the involvement of PGs in immunosuppression and secondary anemia, as well as the efficacy of inhibited overproduction of PGs in many pathologic conditions other than rheumatologic disease.

Effects of heating, storage, and ultraviolet exposure on antimicrobial activity of garlic juice.

This study was designed to investigate the effect of heating, storage, and ultraviolet exposure on antimicrobial activity of garlic juice and its bacteriocidal activity against common human pathogens. Antimicrobial activity of fresh garlic juice was tested against Escherichia coli, Staphylococcus aureus, Streptococcus hemolyticus B, S. hemolyticus A, Klebsiella sp., Shigella dysenteriae, and Candida albicans using the disc method. The dilution method was performed by addition of garlic juice to broth media to obtain 1-100% concentrations as vol/vol or wt/vol. Garlic juice was used after 24 hours of storage at 4 degrees C, heating to 100 degrees C for 5 minutes, 10 minutes, 30 minutes, and 60 minutes, heating to 80 degrees C for 60 minutes, and 4 hours of exposure to ultraviolet light. Re-culture of specimens taken from garlic-induced negative media was performed in fresh broth free of garlic juice. Results showed that all the isolates were sensitive to fresh garlic juice; the most sensitive was C. albicans, and the least sensitive was S. hemolyticus A. Heating to 100 degrees C for 30 and 60 minutes completely abolished the antimicrobial activity, while heating for 5 and 10 minutes, storage for 24 hours, and 4 hours of ultraviolet exposure decreased it. Garlic juice was bactericidal at concentrations of 5% and more. Thus garlic juice has marked antimicrobial activity that makes it a potential agent to be tested in clinical trials. The antimicrobial activity was compromised by storage and heating; therefore it is advisable to use fresh garlic and avoid boiling it for more than 5 minutes during cooking.

Honey ameliorates influence of hemorrhage and food restriction on renal and hepatic functions, and hematological and biochemical variables.

The objectives were to assess the effects of various diets, including total food restriction with 50% honey feeding, total food restriction with 50% dextrose feeding or adlibitum (control group) commercial regular diet, on the hematology and biochemical variables, and to assess the effects of the various diets on the influence of acute blood loss on the same parameters. Thirty Sprague-Dawley albino rats were divided into three groups, 10 rats each: group A, fed a commercial regular diet; group B, total food restriction with 50% dextrose feeding; and group C, total food restriction with 50% honey feeding. After 8 days of feeding, rats were subjected to acute blood loss (6 ml/kg) and blood investigations were performed. After acute blood loss, the same feedings were continued for a further 8 days and the blood tests were repeated at day 8 post-bleeding. Total food restriction with 50% dextrose feeding compared with commercial regular diet reduces hematological and biochemical variables. Total food restriction with 50% honey feeding compared with total food restriction with 50% dextrose feeding causes a greater reduction in fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and triacylglycerol. Acute blood loss causes elevation of white blood cells, lymphocyte percentage, fasting blood sugar, blood urea nitrogen, alkaline phosphatase and triacylglycerol, and a reduction in serum albumen, protein, cholesterol, AST, serum creatinine and hemoglobin; the results are significant (P<0.05) concerning fasting blood glucose, AST, alkaline phosphatase, serum albumin and protein. A significant reduction in fasting blood glucose, white blood cells, BUN, AST, ALT, alkaline phosphatase and triacylglycerol, and a significant elevation of hemoglobin and serum albumin are obtained after acute blood loss in rats on total food restriction with 50% honey feeding as compared with the other two groups. Total food restriction with 50% honey feeding increases serum albumin, serum protein, fasting blood glucose, and causes lower reduction in hemoglobin as compared with the other groups. Conclusively, honey feeding during total food restriction significantly modifies and ameliorates biochemical and hematological changes observed after acute blood loss. This will pave the way to use honey as part of bleeding management and during a food restriction regimen.

Influence of various diet regimens on deterioration of hepatic function and hematological parameters following carbon tetrachloride: a potential protective role of natural honey.

The objective was to assess the effects of commercial regular diet as control, total food restriction with honey, commercial regular diet with dextrose, or total food restriction with dextrose, on blood variables after carbon tetrachloride (CCl4) administration. Sprague Dawley albino rats were divided into four groups, 10 rats each; Group 1 rats were on commercial regular diet, Group 2 rats were on commercial regular diet with 50% dextrose, Group 3 rats were on total food restriction with 50% dextrose, and Group 4 rats were on total food restriction with 50% honey. Rats in all the groups were i.m. administered CCL4 (2.4 mL kg b. wt.-1). Blood tests including ALT, AST, serum albumin, serum protein, BUN, blood glucose (BG), hemoglobin (Hb), and white blood cell (WBC) were performed before CCl4 administration and repeated after 48 and 96 h of post-injection. In Group 1, CCl4 caused significant elevation in AST and ALT, and decrease in BS, WBC, and BUN; lower elevation in AST and ALT at 48 h and decreased AST and ALT at 96 h were obtained when dextrose was added to commercial regular diet (Group 2). Using dextrose alone (Group 3), though there was significant elevation of AST and ALT and decrease in BUN and WBC as compared to baseline values, significant decrease in ALT, AST, and BUN as compared to control was obtained. During absolute honey feeding (Group 4), elevation in AST and ALT obtained, following CCl4 administration was significantly less than the values obtained in all other groups; with lower elevation in AST and ALT as compared to baseline values. Honey increased serum albumin, serum protein, BG, and caused lower reduction in Hb. Conclusively, exclusive honey feeding (50% concentration) significantly modifies and ameliorates biochemical and hematological changes obtained after CCl4 injection.

Effect of carbamazepine on urinary volume and osmolality, water clearance, and serum osmolality in patients with primary enuresis.

OBJECTIVE: In this study we investigate the effects of carbamazepine (CBZ) on urinary volume, frequency of micturition, serum and urine osmolality, osmotic and creatinine clearance, and free water clearance in patients with primary nocturnal enuresis. This information might help in our understanding of the mechanism of action of CBZ in management of patients with enuresis. PATIENTS AND METHODS: The study comprised eight patients with primary enuresis (age range, 8-14 yr) who wet at night on a daily basis. Enuretics were given, CBZ 200 mg each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes, osmotic clearance, fractional excretion of sodium, and free water clearance were assayed before CBZ treatment and after 15 d of treatment. Frequencies of bed-wetting and dry nights were observed during treatment. RESULTS: Mean number (+/-SD) of dry nights was increased from zero dry nights (daily bed-wetting) to 9.7 (2.8) per 15 d of treatment (65%). CBZ decreased the 24-h urinary volume by 41%, the night volume by 45%, the day volume by 38%, and frequency of micturition by 28%. CBZ increased the 24-h urinary osmolality by 43%. Serum osmolality changed significantly from 283.7 mOsm/l to 277.2 mOsm/l. CBZ decreased osmotic clearance by 37% and free water clearance by 34%. Creatinine clearance was decreased by 19% after CBZ treatment (p < 0.05). CONCLUSION: CBZ reduced urine volume, increased urine osmolality, and decreased the free water clearance, the osmotic clearance, and the frequency of micturition in enuretics; this might help in understanding its mechanism of action.

Influence of natural honey on biochemical and hematological variables in AIDS: a case study.

Honey lowers prostaglandins and elevates nitric oxide (NO) in various biological fluids in normal persons. NO and prostaglandin play a role in pathogenesis of AIDS. The study was designed to assess the effect of natural honey on prostaglandins and NO levels, blood indices and biochemical tests in a 40 year-old woman with AIDS. This presentation is a case story of a 40 year-old women with a long history of AIDS treated with 80 g of natural honey. Plasma and urinary prostaglandin F2 alpha and thromboxane B2 levels, plasma, urine and saliva content of NO-end product (total nitrite) and hematological tests were estimated before and 3 hours after oral consumption of 80 g of natural honey. These variables, in addition to biochemical tests, were re-estimated after 21 days of daily consumption of 80 g of natural honey. Results showed that prostaglandins level compared with normal subjects were elevated in patient with AIDS. Natural honey decreased prostaglandins levels, and elevated NO-end product, percentage of lymphocytes, platelet count, and serum protein, albumin and copper levels. It might be concluded that natural honey decreased prostaglandins level, elevated NO production and improved hematological and biochemical tests in a patient with a long history of AIDS.

The safety and efficacy of a mixture of honey, olive oil, and beeswax for the management of hemorrhoids and anal fissure: a pilot study.

We have found that a mixture of honey, olive oil, and beeswax was effective for treatment of diaper dermatitis, psoriasis, eczema, and skin fungal infection. The mixture has antibacterial properties. A prospective pilot study was conducted to evaluate the therapeutic effect of topical application of the mixture on patients with anal fissure or hemorrhoids. Fifteen consecutive patients, 13 males and 2 females, median age 45 years (range: 28-70), who presented with anal fissure (5 patients) or first- to third-degree hemorrhoids (4 with first degree, 4 with second degree, and 2 with third degree), were treated with a 12-h application of a natural mixture containing honey, olive oil, and beeswax in ratio of 1:1:1(v/v/v). Bleeding, itching, edema, and erythema were measured using a scoring method: 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. The pain score was checked using a visual analog scale (minimum = 0, maximum = 10). Efficacy of treatment was assessed by comparing the symptoms' score before and after treatment; at weekly intervals for a maximum of 4 weeks. The patients were observed for evidence of any adverse effect such as appearance of new signs and symptoms, or worsening of the existing symptoms. The honey mixture significantly reduced bleeding and relieved itching in patients with hemorrhoids. Patients with anal fissure showed significant reduction in pain, bleeding, and itching after the treatment. No side effect was reported with use of the mixture. We conclude that a mixture of honey, olive oil, and beeswax is safe and clinically effective in the treatment of hemorrhoids and anal fissure, which paves the way for further randomized double blind studies.

Urinary nitrite excretion and urinary variables in patients with primary nocturnal frequency of micturition: effects of indomethacin suppositories.

Urinary nitrite excretion was measured in patients with primary nocturnal frequency of micturition (PNFM) and in normal individuals. Effects of indomethacin suppository on urine volume and other urinary variables were evaluated. The study comprised seven patients with PNFM and seven healthy control (age range 30-45 years). Nitrite was assayed in spot morning urine samples; urine volume, urine osmolality and electrolytes, serum osmolality and electrolytes and functional bladder capacity (FBC) were assayed. Both groups were then given 100 mg of indomethacin suppository daily for a maximum of 10 days and urinary variables were re-evaluated during day 10. Results showed that urinary nitrite excretion of patients with PNFM was greater than that of the normal subjects (230+/-62 umol/l vs. 42+/-30 umol/l, P<0.05). The mean (SD) 24 h urine volume and osmolality, the night urine volume and osmolality, serum osmolality, FBC, creatinine clearance, fractional excretion of sodium (FENa), fractional excretion of potassium (FEK), and urinary excretion of glucose and potassium were lower in patients with PNFM as compared with normal individuals, although not statistically significantly so, except for FBC that was significantly lower in the patients. Urinary excretion of sodium, calcium, chloride, phosphorus, magnesium, day-night urinary volume ratio, spot morning osmolality, nocturnal index, and nocturnal polyuria index were higher in patients with PNFM. Indomethacin decreased the 24 h urinary volume by 21%, creatinine clearance by 12%, osmolar clearance by 14% and urinary protein excretion by 38% in the patients. These variables decreased by 26, 45, 17 and 12% respectively in the healthy subjects, whereas 24 h urinary protein excretion increased mildly by 9%. Indomethacin increased day-night urinary volume ratio by 73% in the healthy subjects. It might be concluded that urinary nitrite excretion, urinary excretion of sodium, chloride, phosphorus, calcium, and magnesium increased and FBC decreased in patients with PNFM; Indomethacin decreased urinary volume, FENa, FEK, osmolar clearance, and free water clearance in the healthy subjects and the patients. These might explain the mechanism of action of indomethacin to reduce frequency of voiding. The possible interaction of prostaglandin and NO in the pathogenesis of PNFM is discussed.