Protective Effect of Carvacrol on Oxidative Stress and Cellular DNA Damage Induced by UVB Irradiation in Human Peripheral Lymphocytes.

Exposure to ultraviolet B (UVB; 280-320 nm) radiation induces the formation of reactive oxygen species (ROS) in the biological system. In this study, we examined the protective effect of carvacrol on UVB-induced lipid peroxidation and oxidative DNA damage with reference to alterations in cellular an-tioxidant status in human lymphocytes. A series of in vitro assays (hydroxyl radical, superoxide, nitric oxide, DPPH (2,2-Diphenyl-1-picryl hydrazyl), and ABTS (2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays) demonstrate antioxidant property of carvacrol in our study. UVB exposure significantly increased thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHPs), % tail DNA and tail moment; decreased % cell viability and antioxidant status in UVB-irradiated lymphocytes. Treatment with carvacrol 30 min prior to UVB-exposure resulted in a significant decline of TBARS, LHP, % tail DNA, and tail moment and increased % cell viability as carvacrol concentration increased. UVB irradiated lymphocytes with carvacrol alone (at 10 µg/mL) gave no significant change in cell viability, TBARS, LHP, % tail DNA, and tail moment when compared with normal lymphocytes. On the basis of our results, we conclude that carvacrol, a dietary antioxidant, mediates its protective effect through modulation of UVB-induced ROS.

Antihyperglycemic effect of carvacrol in combination with rosiglitazone in high-fat diet-induced type 2 diabetic C57BL/6J mice.

Thiazolidinediones constitute a family of antidiabetic drugs, and rosiglitasone (RSG) has an extensive usage in treating the complications of type 2 diabetes mellitus. Carvacrol (CVL), a monoterpenic phenol that occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species, possess a wide variety of pharmacological properties including antioxidant potential. We hypothesized that carvacrol in combination with RSG would prove beneficial to ameliorate the dysregulated carbohydrate metabolism in high-fat diet (HFD)-induced type 2 diabetic C57BL/6J mice. Mice were divided into six groups and fed HFD, for 10 weeks. CVL (20 mg/kg BW) and RSG (4 mg/kg BW) were administered post-orally, daily for 35 days. HFD mice showed an elevation in plasma glucose, insulin, glycosylated hemoglobin and a decrease in hemoglobin. The activities of carbohydrate metabolic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase increased whereas glucokinase and glucose-6-phosphate dehydrogenase activities decreased in the liver of HFD mice. The activities of hepatic marker enzymes such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase increased in HFD mice. Combination of CVL and RSG prevented the above changes toward normalcy. Histopathological analysis of H&E stained pancreas was also in agreement with the biochemical findings. These major findings provide evidence that combination of CVL with RSG has better antidiabetic properties.

Modulatory effect of sesamol on DOCA-salt-induced oxidative stress in uninephrectomized hypertensive rats.

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180-200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects.

Ursolic acid and rosiglitazone combination alleviates metabolic syndrome in high fat diet fed C57BL/6J mice.

The aim of this study was to examine the combined effect of ursolic acid (UA) and rosiglitazone (RSG) on metabolic syndrome in C57BL/6J mice. Upon feeding high fat diet (HFD) C57BL/6J mice developed obesity, insulin resistance, dyslipidemia and hypertension. The male mice were randomly divided into six groups, and fed normal diet, normal diet plus UA and RSG, HFD alone, HFD plus UA, HFD plus RSG, and HFD plus UA and RSG, respectively. HFD fed mice showed increase in body weight, elevated plasma glucose and insulin. Activities of gluconeogenic enzymes such as glucose 6-phosphatase, fructose 1,6-bisphosphatase increased while the activity of glycolytic enzyme, glucokinase, decreased in the liver along with glycogen content. Total cholesterol, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol and free fatty acid levels significantly increased in the plasma, whereas high-density lipoprotein cholesterol significantly decreased in high fat diet fed mice. In addition, both systolic and diastolic blood pressure was increased significantly. Combined treatment with UA and RSG improved the above parameters towards normality and pronounced more responses than UA or RSG lone treatment. The inclusion of UA in treatment with RSG may reduce the body weight gain, one of adverse side effect associated with the RSG-therapy.

Antioxidative and hypolipidemic efficacy of alcoholic seed extract of Swietenia macrophylla in streptozotocin diabetic rats.

The present study was designed to examine the antioxidative potential and antihyperlipidemic activity of Swietenia macrophylla in streptozotocin diabetic rats. The experimental groups were rendered diabetic by intraperitoneal injection of a single dose of streptozotocin (STZ; 40 mg/kg body weight, BW). Rats with glucose levels >200 mg/dL were considered diabetic and were divided into five groups. Three groups of diabetic animals were orally administered daily with seed extract (SME) at a dosage of 50, 100 and 200 mg/kg BW. One group of STZ rats was treated as diabetic control and another group orally administered 600 µg/kg BW glibenclamide daily. Repeated daily oral administration of S. macrophylla significantly reduced blood glucose levels after 45 days of treatment. The lipid peroxidation products such as thiobarbituric acid reactive substances and lipid hydroperoxides of SME treated rats decreased in the plasma, liver and kidney. Glutathione peroxidase, superoxide dismutase and catalase activity were significantly increased in SME treated rats. Antioxidants such as reduced glutathione level in the plasma, liver and kidney and vitamins C and E levels in the plasma increased in SME treated rats. Total cholesterol, triglycerides, phospholipids and free fatty acids and lipoproteins levels increased. Altered lipid profile of treated rats lead to normality with treatment of S. macrophylla. Thus, our results indicate that the administration of 100 mg/kg BW SME restores near normal blood glucose, redox status and lipid profile in STZ-diabetic rats.

Antihyperlipidemic activity of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, in streptozotocin-diabetic rats.

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on carbohydrate metabolism was investigated, and its antihyperglycemic effect was shown previously (Chandramohan et al., Eur J Pharmacol 2008;590:437-443). In this study we investigated the effect of 3-HMX on plasma and tissue lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. The normal and diabetic rats were treated with 3-HMX (40 mg/kg BW/day) for 45 days. The levels of total cholesterol, triglycerides, free fatty acids, and phospholipids were assayed in the plasma besides lipoprotein-cholesterol (high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very low density lipoprotein-cholesterol (VLDL-C)) and tissues (liver, kidney, heart, and brain). Total cholesterol, triglyceride, free fatty acid, and phospholipid (LDL-C and VLDL-C in plasma only) levels increased in plasma and tissues significantly, whereas plasma HDL-C significantly decreased in diabetic rats. Treatment with 3-HMX or glibenclamide reversed the above-mentioned changes and improved toward normalcy. Histological study of liver also confirmed the biochemical findings. Thus administration of 3-HMX is able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.

Antihyperglycemic effect of protocatechuic acid on streptozotocin-diabetic rats.

Protocatechuic acid (PCA) (3,4-dihydroxybenzoic acid), a natural phenolic compound found in many edible and medicinal plants, is a major benzoic acid derivative with a strong antioxidative effect, 10-fold higher than that of alpha-tocopherol. The present study is aimed at evaluating the antidiabetic effect of PCA on STZ-diabetic rats. Diabetes was induced in male albino Wistar rats by the administration of STZ (40 mg/kg BW, i.p.). PCA was administered orally at three different doses (50, 100, 200 mg/kg BW/day) to STZ-diabetic rats for 45 days. Diabetic rats showed increase in plasma glucose and glycosylated hemoglobin (HbA1c) and a decrease in plasma insulin and hemoglobin (Hb). The activities of gluconeogenic enzymes like glucose 6-phosphatase and fructose 1,6-bisphosphatase increased whereas the glycolytic enzyme glucokinase decreased in the liver along with glycogen content. The oral administration of PCA or glibenclamide in saline, for 45 days, prevented the changes and improved toward normalcy. No significant effect was observed in normal rats treated with PCA. Thus, our results show that PCA at 100 mg possesses a potential antihyperglycemic effect that is comparable with glibenclamide.

In vivo antioxidant and hypolipidemic effect OF Cardiospermum halicacabum leaf extract in streptozotocin-induced diabetic rats.

In this study we investigated the antioxidant and antihyperlipidemic of an ethanolic leaf extract of Cardiospermum halicacabum (CHE) in plasma and tissues of streptozotocin (STZ)-induced diabetic rats. The plasma and tissue concentrations of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide were significantly elevated in STZ diabetic rats. CHE administration decreased TBARS and lipid hydroperoxide levels. The plasma vitamin E level increased and the vitamin C level decreased. The reduced glutathione level significantly decreased in plasma and tissues, as did the activities of enzymatic antioxidants. The enzymatic and non enzymatic alterations reversed toward normalcy after treatment with CHE. STZ-induced diabetic rats showed significant increases in plasma total cholesterol, phospholipids, triglycerides, and free fatty acids, which returned to near normalcy in CHE-treated animals. Plasma LDL-C and VLDL-C increased and HDL-C decreased and both reverted to near normalcy following CHE treatment. We conclude that CHE possesses antioxidant and hypolipidemic effects in diabetic rats, which may be due to the presence of flavonoids, such as apigenin and luteolin in the extract.

Antihypertensive efficacy of Melothria maderaspatana leaf extract on sham-operated and uninephrectomized DOCA-salt hypertensive rats.

The plant Melothria maderaspatana (MME) has been used traditionally as antihypertensive and has been proven scientifically to possess high antioxidant and hepatoprotective activity. The present study has been designed to investigate the antihypertensive effect of ethanolic extract of MME leaves on sham-operated and uninephrectomized DOCA-salt-induced hypertensive male albino Wistar rats. A midscapular incision was made on each rat and the left kidney was excised after ligation of the renal artery. The surgical wound was closed using a suture. After one week recovery period, hypertension was induced by subcutaneous injection of DOCA-salt solution, twice a week, and the rats received a 1% sodium chloride solution as drinking water throughout the experimental period. After 6 weeks injection of DOCA-salt, systolic, diastolic and mean arterial blood pressure was significantly elevated as compared with sham-operated control. Treatment with MME significantly decreased theblood pressure. Thus, the results show that MME possesses antihypertensive activity in DOCA-salt hypertensive rats.

Anthropometric parameters, lipid peroxidation and antioxidants in auto-rickshaw drivers.

Anthropometric and several biochemical parameters were estimated in smoking and alcoholic-smoking auto-drivers and compared with normal auto-rickshaw drivers and normal subjects. Auto-drivers had a lower height, weight, and body mass index (BMI) compared with age-matched normal subjects. Plasma thiobarbituric acid reactive substances (TBARS), total cholesterol, TC/HDL-C ratio, and lactic acid increased significantly and ascorbic acid, alpha-tocopherol, reduced glutathione (GSH), hemoglobin, and HDL-cholesterol decreased significantly in auto-drivers when compared with normal subjects. Total cholesterol and TC/HDL-C ratio increased significantly in smoking auto-drivers; TBARS increased and ascorbic acid, alpha-tocopherol, GSH, and hemoglobin decreased significantly in alcoholic-smoking auto-drivers. Exposure of automobile pollutants associated with habits (cigarette smoking, alcohol) causes profound alterations in the levels of lipid peroxidation, antioxidants, hemoglobin, total cholesterol, HDL-cholesterol, TC/HDL-C ratio and lactic acid.

Antihyperlipidemic effect of carvacrol on D-galactosamine-induced hepatotoxic rats.

Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic phenol occuring in many essential oils of the family Labiatae including, Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. The present study was designed to investigate the effect of carvacrol on D-galactosamine (D-GalN)-induced hepatotoxicity in rats. D-GalN-hepatotoxic rats exhibited elevation in the serum bilirubin level and the activities of the hepatic marker enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase. In the plasma, increased levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol and decreased high density lipoprotein cholesterol were observed. Further, an increase in the levels of total cholesterol, phospholipids, triglycerides, and free fatty acids in the plasma and tissues of liver and kidney were observed in hepatotoxic rats. The administration of carvacrol for 21 days prevented and improved these parameters toward normalcy. The results suggest that carvacrol affords a significant hepatoprotective and hypolipidemic effect against D-GalN-induced-rats.

Oxidative stress, antioxidant status and lipid profile in pulmonary tuberculosis patients before and after anti-tubercular therapy.

BACKGROUND: Pulmonary tuberculosis (PTB) is a highly infectious dreadful disease caused by mycobacterium tuberculosis (MTB). Numerous studies reported free radicals activity, antioxidant status and lipid profile in PTB patients, but previous studies have lacunae in comparing the biochemical variables between before and after anti-tubercular therapy (ATT) supplementation to PTB patients. Hence, the present study was carried out to investigate oxidative stress markers, antioxidant status, lipid profile, liver function markers, and glycoprotein components in pulmonary tuberculosis patients (PTB) patients before and after 60 days of ATT. METHODS: This is a case-control study carried out with 100 healthy subjects and 110 PTB patients. All the patients diagnosed with sputum test and were positive for acid fast bacilli (AFB) were included for the study. An informed consent was obtained from all the patients. RESULTS: Our study found increased levels of oxidative stress markers, decreased enzymatic and non-enzymatic antioxidants, altered lipid profile in PTB patients as compared to healthy subjects before treatment and these levels were restored after clinical improvement with ATT. We also found increased concentrations of liver function parameters and components of glycoprotein in PTB patients. ATT refurbished lipid levels, antioxidant status and oxidative stress markers with decrease in liver function enzymes and glycoproteins in PTB patients. CONCLUSION: Co-supplementation of antioxidants, along with ATT and inclusion of nutritious diet could be useful to reduce the pathogenesis of PTB and is warranted as a future study for the management of PTB.

A novel compound from Casearia esculenta (Roxb.) root and its effect on carbohydrate metabolism in streptozotocin-diabetic rats.

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound 3-hydroxymethyl xylitol (3-HMX) has been isolated and its optimum dose has been determined in a short duration study and patented. In the present study, the long-term effect of 3-HMX in type 2 diabetic rats has been investigated. An optimum dose of 3-HMX (40 mg/kg body weight) was orally administered for 45 days to streptozotocin-diabetic rats for the assessment of glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA(1c)), hepatic glycogen, and activities of carbohydrate metabolizing enzymes, such as glucokinase, glucose 6-phosphatase, fructose 1,6-bisphosphatase and glucose-6-phosphate dehydrogenase and hepatic marker enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT) in normal and streptozotocin-diabetic rats. 3-HMX at 40 mg dose produced similar effects on all biochemical parameters studied as that of glibenclamide, a standard drug. Histological study of pancreas also confirmed the biochemical findings. These results indicate that 3-hydroxymethyl xylitol, the compound from C. esculenta, possesses antihyperglycemic effect on long-term treatment also.

Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in D-galactosamine-induced hepatotoxic rats.

D-galactosamine is a well-established hepatotoxicant that induces a diffuse type of liver injury closely resembling human viral hepatitis. D-galactosamine by its property of generating free radicals causes severe damage to the membrane and affects almost all organs of the human body. The leaves of Piper betle L., a commonly used masticatory in Asian countries, possess several biological properties. Our aim is to investigate the in vivo antioxidant potential of P. betle leaf-extract against oxidative stress induced by D-galactosamine intoxication in male albino Wistar rats. Toxicity was induced by an intraperitoneal injection of D-galactosamine, 400 mg/kg body weight (BW) for 21 days. Rats were treated with P. betle extract (200 mg/kg BW) via intragastric intubations. We assessed the activities of liver marker enzymes (aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase) and levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione. The extract significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, and liver marker enzymes when compared with the D-galactosamine treated group, demonstrating its hepatoprotective and antioxidant properties.

Protective effect of Umbelliferone on membranous fatty acid composition in streptozotocin-induced diabetic rats.

Umbelliferone (UMB), a natural antioxidant, is benzopyrone in nature, and it is present in the fruits of golden apple and bitter orange. Earlier we evaluated and reported the effect of Umbelliferone on antidiabetic, antioxidant and antihyperlipidemic properties, and this study was designed to evaluate the effect of Umbelliferone on membrane fatty acid composition and histopathology of liver and kidney of control and streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by an intraperitonial administration of STZ (40 mg/kg). The control and diabetic rats were treated with Umbelliferone and glibenclamide dissolved in 10% dimethyl sulfoxide for 45 days. Diabetic rats had decreased insulin and increased glucose, and increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes. The levels of palmitic, stearic and oleic acids increased and the levels of linolenic and arachidonic acids decreased in diabetic rats as compared with control rats. Thus, the saturated fatty acids and monounsaturated fatty acids increased and the polyunsaturated fatty acids decreased in diabetic rats. Diabetic rats had decreased liver weight and increased activities of alanine transaminase and aspartate transaminase; increased kidney weight and urine albumin, and decreased levels of urea, uric acid and creatinine in the urine. Histopathological studies of liver and kidney in diabetic rats showed fatty changes surrounding portal triad; enlargement of lining cells of tubules, fatty infiltration, large area of hemorrhage and lymphocyte infiltration. Treatment with Umbelliferone and glibenclamide reversed these changes to near normalcy. Our results showed that Umbelliferone has a protective effect on membrane fatty acid composition of liver and kidney as supported by antioxidant and antihyperlipidemic effects of Umbelliferone reported earlier as evidenced by improved histopathological changes, hepatic and nephritic markers, indicating recovery from the risk of diabetic complications.

Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocin-diabetic rats.

Diabetes mellitus is known to affect collagen in various tissues. Umbelliferone (7-hydroxycoumarin), a natural antioxidant and benzopyrone, is found in golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Plant-derived phenolic coumarins have been shown to act as dietary antioxidants. In this study, we have investigated the influence of umbelliferone on collagen content and its effects on the tail tendon in streptozotocin-diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by intraperitoneal administration of streptozotocin (40 mg/kg). Normal and diabetic rats were treated with umbelliferone for 45 days. Diabetic rats had increased glucose and decreased insulin levels. Tail tendons of diabetic rats had increased total collagen, glycation and fluorescence, and decreased levels of neutral, acid and pepsin-soluble collagens. We have studied the effect of umbelliferone on haemostatic function because umbelliferone is also a coumarin derivative like the anticoagulant, warfarin. Diabetic rats had a significant decrease in prothrombin, clotting and bleeding time, and treatment with umbelliferone made these parameters almost normal. Our results show that umbelliferone controls glycaemia and has a beneficial effect on collagen content and its properties, i.e. collagen related parameters, in the tail tendon, which indicates recovery from the risk (recovery of animals from the risk of complications) of collagen-mediated diabetic polyneuropathy and diabetic nephropathy.

Effect of Melothria maderaspatana leaf-tea consumption on blood pressure, lipid profile, anthropometry, fibrinogen, bilirubin, and albumin levels in patients with hypertension.

OBJECTIVE: To determine the effect of Melothria maderaspatana (Linn.) leaf-tea on blood pressure, plasma lipid profile, fibrinogen, albumin together with serum bilirubin and anthropometric measurements in volunteer participants with hypertension, because all these variables have been shown to influence vascular events. SUBJECTS AND DESIGN: A total of 50 subjects-25 (mean age of 58 +/- 9.0 years; 12 were women) with mild-to-moderate hypertension (systolic blood pressure [SBP] >or= 140 mm Hg; diastolic blood pressure [DBP] >or= 90 mm Hg) and 25 normotensives (mean age of 48 +/- 8.0 years; 11 women)-were selected for this study. Plasma lipid profile, fibrinogen, albumin, serum bilirubin, and anthropometric measurements were measured at baseline and after leaf-tea consumption by the patient with hypertension for 45 days. RESULTS: SBP and DBP gradually decreased and pulse rate decreased. The total cholesterol, low-density lipoprotein cholesterol and triglycerides, and phospholipids levels decreased significantly and high-density lipoprotein cholesterol and serum bilirubin levels increased after tea consumption in patients with hypertension. We also observed significant body weight loss and reduction in fibrinogen levels. There was no significant difference in plasma level of albumin. CONCLUSIONS: Thus, M. maderaspatana leaf-tea consumption gradually decreased BP and showed beneficial effects on blood lipid profile, fibrinogen, bilirubin, and body mass index in patients with hypertension.

Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats.

Ursolic acid is a triterpenoid that exists in nature and is the major component of some traditional medicinal herbs. In this study, ursolic acid has been evaluated for its hepatoprotective effect against chronic ethanol-mediated toxicity in rats. Ethanol administration (7.9 g/kg/day) for 60 days resulted in increased oxidative stress, decreased antioxidant defense and liver injury. It also negatively affected the serum total protein, albumin and A/G ratio. Subsequent to the experimental induction of toxicity (i.e. after the initial period of 30 days) ursolic acid treatment performed by co-administering ursolic acid (10, 20 and 40 mg/kg body weight) for 30 days along with the daily dose of ethanol. While this treatment causing a significant improvement in body weight, food intake and serum protein levels, it decreases serum aminotransferase activities (aspartate aminotransferase and alanine aminotransferase) and total bilirubin levels. Ursolic acid improved the antioxidant status of alcoholic rats, which is evaluated by the decreased levels of lipid peroxidation markers in plasma (thiobarbituric acid reactive substances and lipid hydroperoxides) and increased levels of circulatory antioxidants such as reduced glutathione, ascorbic acid and alpha-tocopherol. Histopathological observations were also in correlation with the biochemical parameters. The activity of ursolic acid (20 mg/kg) compares well with silymarin, a known hepatoprotective drug, and seems to be better in certain parameters. The protective effect of ursolic acid is probably related to its antioxidant activities.

Ursolic acid and rosiglitazone combination improves insulin sensitivity by increasing the skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat diet-fed C57BL/6J mice.

The aim of this present study was to investigate the effect of ursolic acid (UA) and rosiglitazone (RSG) on insulin sensitivity and proximal insulin signaling pathways in high-fat diet (HFD)-fed C57/BL/6J mice. Male C57BL/6J mice were fed either normal diet or HFD for 10 weeks, after which animals in each dietary group were divided into the following six groups (normal diet, normal diet plus UA and RSG, HFD alone, HFD plus UA, HFD plus RSG, and HFD plus UA and RSG) for the next 5 weeks. UA (5 mg/kg BW) and RSG (4 mg/kg BW) were administered as suspensions directly into the stomach using a gastric tube. The HFD diet elevated fasting plasma glucose, insulin, and homeostasis model assessment index. The expression of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-kinase), Akt, and glucose transporter (GLUT) 4 were determined by Western blot analyses. The results demonstrated that combination treatment (UA/RSG) ameliorated HFD-induced glucose intolerance and insulin resistance by improving the homeostatic model assessment (HOMA) index. Further, combination treatment (UA/RSG) stimulated the IRS-1, PI3-kinase, Akt, and GLUT 4 translocation. These results strongly suggest that combination treatment (UA/RSG) activates IRS-PI3-kinase-Akt-dependent signaling pathways to induce GLUT 4 translocation and increases the expression of insulin receptor to improve glucose intolerance.

Effect of protocatechuic acid on lipid profile and DNA damage in D-galactosamine-induced hepatotoxic rats.

BACKGROUND: Our aim in this study is to investigate the effect of protocatechuic acid (PCA) on lipid profile and DNA damage in D-galactosamine (D-GalN)-induced hepatotoxic rats. METHODS: Hepatotoxicity was induced by a single intraperitoneal dose of D-GalN in male Wistar rats. The activities of hepatic markers and levels of kidney function markers were determined. The plasma and tissue lipid levels were estimated. DNA damage was determined by COMET assay. Histopathological examination was also performed using portions of the liver and kidney tissues. RESULTS: D-GalN-induced hepatotoxic rats showed increased in the activities of hepatic marker enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT) in serum. The levels of kidney function markers such as urea, uric acid, and creatinine increased in serum. Levels of lipid profile such as total cholesterol (TC), triglycerides (TG), free fatty acid (FFA), and phospholipids (PLs) in the plasma and tissues (liver and kidney) were significantly increased in D-GalN-induced rats. In plasma, levels of very low density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) significantly increased, whereas high-density lipoprotein cholesterol (HDL-C) level decreased in D-GalN-induced rats. Furthermore, D-GalN-induced rats showed increased percentage of tail DNA and tail length and decreased percentage of head DNA. Oral administration of PCA (100 mg/ kg BW) for 20 days improved these levels when compared to D-GalN-induced rats. These biochemical changes were reflected on the attenuation and the structural alteration of the liver and kidney integrity. CONCLUSIONS: The results of the study suggest that PCA has a potent hepatoprotective activity that may be linked to its antihyperlipidemic effect.