Pleiotropic effects of Salacia reticulata and Simvastatin on oxidative stress and insulin resistance in a rat model.

BACKGROUND: The present study investigated the effects of Salacia reticulata and simvastatin on oxidative stress and insulin resistance in Sprague-Dawley (SD) rats. We compared the protective effect of a methanolic extract of Salacia reticulata (SR) with simvastatin (SVS) in rats fed a high-fat diet (HFD). METHODS AND RESULTS: Male Sprague-Dawley rats were divided into the following five different groups: control (C), C+SR, HFD, HFD+SR, and HFD+SVS. High-fat diet fed rats showed hyperglycemia, hyperinsulinemia, hyperleptinemia, dyslipidemia, and hypoadiponectinemia after 90 days. Treatment of high-fat diet fed rats with SR/SVS significantly (p < 0.05) reduced high-fat diet induced increases in plasma triglycerides, total cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and decreased high- density lipoprotein (HDL) accompanied by an increase in lipid peroxidation (LPO) and protein oxidation. In addition, a significant decrease in the activities of antioxidant enzymes and enzymes of the polyol pathway was observed in rats fed high-fat diet. SR was found to be more effective than SVS. Moreover, infiltration of inflammatory cells and fibrosis in the liver of high-fat diet fed rats by SR/SVS were also prevented. CONCLUSIONS: The present study confirms that SR/SVS may be a new and promising remedial approach because of its beneficial effects on the pathophysiological processes of obesity and related metabolic disorders.

Preventive effect of Caralluma fimbriata against high-fat diet induced injury to heart by modulation of tissue lipids, oxidative stress and histological changes in Wistar rats.

OBJECTIVE: To investigate whether hydro-alcoholic extract of aerial parts of Caralluma fimbriata (CFE) could attenuate high-fat diet (HFD) induced cardiac damage. METHODS: Forty rats were divided into five groups: control (C), treated with CFE, treated with HFD, HFD treated with CFE, and HFD treated with metformin (Met). RESULTS: CFE treatment significantly (p < .001) attenuated HFD-induced increase in cardiac lipids such as total lipids, triglycerides, total cholesterol, and free fatty acids and decreased phospholipids accompanied by increasing in lipid peroxidation and protein oxidation. Furthermore, significant reduction in the activities of antioxidant enzymes, creatine kinase and aldose reductase and sorbitol dehydrogenase was also observed in HFD fed rats. These changes were alleviated by CFE. Moreover, the histopathological observations of heart are also in agreement with the biochemical findings. CONCLUSION: The present study confirmed that CFE could be used as adjuvant therapy for preventing or managing high fat diet induced cardiac damage.

Cardioprotective effect of Phyllanthus amarus against high fructose diet induced myocardial and aortic stress in rat model.

Increased number of population with heart stroke/attack is attributed to sedentary lifestyle and consumption of high-sugar diets, especially fructose. The objective of this study is to investigate the cardio-protective activity of aqueous extract of Phyllanthus amarus (PAAE) against high-fructose (HF) diet induced cardiac damage in Wistar rats. Male Wistar rats were randomly assigned into five groups of six animals each: Control (C), Control treated with PAAE (C+PAAE), High fructose diet fed (F), High fructose diet fed treated with PAAE (F+PAAE) and High fructose diet fed treated with Pioglitazone (F+Pio). PAAE was orally administered at a dosage of 200mg/kg body weight/day to C+PAAE and F+PAAE group rats for 60days. Pioglitazone (10mg/kg body weight/day) was used to compare the efficacy of PAAE. After 60days, heart and aorta samples were collected for biochemical and histological analysis. Co-administration of PAAE along with HF-diet for 60days prevented the increase in levels of cardiac and aortic lipids i.e., total lipids, triglycerides, total cholesterol and free fatty acids and decreased phospholipids. Further, enhanced activities of cardiac aldose reductase (15.3%) and sorbital dehydrogenase (6.9%) and decreased activity of creatine kinase (35.6%) in group-F were also prevented by PAAE treatment with the recovery of 126% for AR, 122% for SDH and 118% for CK. PAAE treatment showed protection from HF-diet induced increase in stress markers (LPO and PO), decreased non-enzymatic (GSH and Vit-C) and enzymatic (GR, GPx, GST, SOD, and CAT) antioxidants in the heart and aorta. Histopathological examination of the heart and aorta indicated that PAAE/Pio treatment reduced fat deposition and necrosis. The present study clearly indicates the cardio protection efficacy of PAAE against HF-diet induced oxidative stress in rats.

Modulatory effects of Caralluma fimbriata extract against high-fat diet induced abnormalities in carbohydrate metabolism in Wistar rats.

The present study was aimed to evaluate the modulatory effects of hydroalcoholic extract of Caralluma fimbriata (CFE) by assaying the activities of key enzymes of carbohydrate metabolism and changes in glycogen content (liver and muscle) in high-fat (HF) diet-induced diabetic rats. In vitro glucose uptake studies were carried out in both psoas muscle and adipose tissue. The inhibitory effect of the extract on α-amylase was determined in in vitro studies. Male Wistar rats of body weight around 180g were divided into five groups (n=8), two of these groups were fed with standard pellet diet and the other three groups were fed with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of standard pellet diet rats and HF-fed rats and Metformin (Met) (20mg/kg body weight/day) was administered through oral route to HFD+Met group for 90 days. At the end of the experimental period, biochemical parameters related to glycogen content in liver and muscle, and intestinal disaccharidases like maltase, sucrase and lactase were assayed. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphorfructoki nase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase), intestinal disaccharidases and glycogen content as observed in the high fat diet-fed rats were prevented with CFE/Met administration. From this study, we observed that CFE/Met could significantly restore the levels of glycogen in liver and muscle and key enzymes of carbohydrate metabolism to near normal in groups-HFD+CFE and HFD+Met. The skeletal muscle of HF-diet fed rats showed degenerative changes of muscle myofibers with fat deposition. These changes were attenuated in the HFD group treated with CFE/Met and retained their normal structure appearance. It can be concluded from these results that CFE might be of value in reducing the alterations related to carbohydrate metabolism under high calorie diet consumption.

Beneficial Effects of Phyllanthus amarus Against High Fructose Diet Induced Insulin Resistance and Hepatic Oxidative Stress in Male Wistar Rats.

Insulin resistance (IR) is a characteristic feature of obesity, type 2 diabetes mellitus, and cardiovascular diseases. Emerging evidence suggests that the high-fructose consumption is a potential and important factor responsible for the rising incidence of IR. The present study investigates the beneficial effects of aqueous extract of Phyllanthus amarus (PAAE) on IR and oxidative stress in high-fructose (HF) fed male Wistar rats. HF diet (66% of fructose) and PAAE (200 mg/kg body weight/day) were given concurrently to the rats for a period of 60 days. Fructose-fed rats showed weight gain, hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired insulin sensitivity, dyslipidemia, hyperleptinemia, and hypoadiponectinemia (P < 0.05) after 60 days. Co-administration of PAAE along with HF diet significantly ameliorated all these alterations. Regarding hepatic antioxidant status, higher lipid peroxidation and protein oxidation, lower reduced glutathione levels and lower activities of enzymatic antioxidants, and the histopathological changes like mild to severe distortion of the normal architecture as well as the prominence and widening of the liver sinusoids observed in the HF diet-fed rats were significantly prevented by PAAE treatment. These findings indicate that PAAE is beneficial in improving insulin sensitivity and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

Preventive effect of Caralluma fimbriata vs. Metformin against high-fat diet-induced alterations in lipid metabolism in Wistar rats.

The objective of the present study was to investigate the preventive effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) and Metformin (Met) against high-fat diet (HF-diet) induced alterations in lipid metabolism in Wistar rats. The experimental animals were divided into five groups, two of which were fed with chow diet and the other three with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of chow-fed rats, HF-fed rats and Met (20mg/kg body weight/day) to one of the HF-diet fed groups. At the end of 90days of experimental period, hypercholestermia, hypertriglycerdemia, with decreased HDL-cholesterol and increased LDL, VLDL-cholesterol and atherogenic index and elevated levels of serum and hepatic transaminases and hepatic lipids (p<0.05) and alterations in the activities of enzymes of lipid metabolism, and the liver showed mild to severe distortion of the normal architecture as well as prominence and widening of the liver sinusoids as observed in HF-fed rats, were prevented by CFE/Met treatment. The results showed that CFE/Met supplementation ameliorated significantly the disturbance in serum and hepatic transaminases, plasma and hepatic lipid profile and lipid metabolism under HF-fed conditions. It can be concluded from these results that CFE might be valuable in reducing the alterations related to lipid metabolism under high calorie diet consumption.

Protective effect of Caralluma fimbriata against high-fat diet induced testicular oxidative stress in rats.

High-fat diet (HFD) promotes the oxidative stress formation, which in turn has hazardous effects on reproductive system and fertility. The objective of this study was to evaluate the protective effect of Caralluma fimbriata on high-fat diet-induced oxidative stress in the testis of rat. Male Wistar rats were randomly divided into five groups: Control (C), Control treated with CFE (C+ CFE), High fat diet fed (HFD), High fat diet fed treated with CFE (HFD+CFE) and High fat diet fed treated with Metformin (HFD+Met). CFE was orally administered (200mg/kg body weight) for 90days to groups-C+CFE and HFD+CFE rats. The effects of HF-diet on the reproductive organs were determined by measuring relative and absolute testes and epididymal fat pads weights. Regarding testes antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation, polyol pathway enzymes and lower GSH levels and lower activities of antioxidants, while CFE treatment prevented all these observed abnormalities. The present study clearly indicates that CFE offers a significant protection against HF-diet induced testicular oxidative stress in rats.

Renoprotective effect of Caralluma fimbriata against high-fat diet-induced oxidative stress in Wistar rats.

The current study was designed to evaluate the renoprotective effect of hydro-alcoholic extract of Caralluma fimbriata (CFE) against high-fat diet-induced oxidative stress in Wistar rats. Male Wistar rats were randomly divided into five groups: control (C), control treated with CFE (C + CFE), high-fat diet fed (HFD), high-fat diet fed treated with CFE (HFD + CFE), and high-fat diet fed treated with metformin (HFD + metformin). CFE was orally administered (200 mg/kg body weight) to Groups C + CFE and HFD + CFE rats for 90 days. Renal functional markers such as, urea, uric acid, and creatinine levels in plasma were quantified during the experimental period. At the end of the experimental period, activities of transaminases and oxidative stress markers, i.e., reduced glutathione (GSH), lipid peroxidation, protein oxidation, and activities of antioxidant enzymes were assayed in renal tissue. Coadministration of CFE along with HF-diet in Group HFD + CFE prevented the rise in the levels of plasma urea, uric acid, and creatinine, and elevated activities of renal transaminases with decreased protein content of Group HFD (p < 0.05). Establishment of oxidative stress in Group HFD, as evident from elevated lipid peroxidation, protein oxidation levels with depleted levels of GSH, and decreased activities of GSH dependent and independent antioxidant enzymes, was prevented in Groups HFD + CFE and HFD + metformin rats. Further, there were no deviations in the studied parameters but there was improved antioxidant status of Group C + CFE from Group C which revealed the nontoxic nature of CFE even under chronic treatment. Thus, CFE treatment effectively alleviated the HF-diet induced renal damage. Hence, this plant could be used as an adjuvant therapy for the prevention and/or management of HF-diet induced renal damage.

Abnormalities in carbohydrate and lipid metabolisms in high-fructose dietfed insulin-resistant rats: amelioration by Catharanthus roseus treatments.

High intake of dietary fructose has been shown to exert a number of adverse metabolic effects in humans and experimental animals. The present study was proposed to elucidate the effect of Catharanthus roseus (C. roseus) leaf powder treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats of body weight around 180 g were divided into four groups, two of these groups (groups C and C+CR) were fed with standard pellet diet and the other two groups (groups F and F+CR) were fed with high-fructose (66 %) diet. C. roseus leaf powder suspension in water (100 mg/kg body weight/day) was administered orally to group C+CR and group F+CR. At the end of a 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. roseus treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F was significantly decreased with C. roseus treatment in group F+CR. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. roseus treatment in group F+CR. In conclusion, our study demonstrates that C. roseus treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose-induced alterations in carbohydrate and lipid metabolisms. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats.

BACKGROUND AND OBJECTIVES: The present study investigated the effect of Commiphora mukul ethanol extract gum resin (CMEEt) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, plasma insulin, plasma lipid profile, atherogenic index, hepatic lipid peroxidation (LPO), protein oxidation (PO) and activities of enzymatic antioxidants. METHODS: Wistar albino rats were divided into 4 groups, normal control group, CM-treated control group, diabetic control group and CM-treated diabetic group. For induction of diabetes, STZ was administered at a dose of 55mg/kg body weight, meanwhile CM-treated groups were administered CMEEt at a dose of 200mg/kg body weight for 60 days. Body weight, plasma glucose and insulin levels were determined in different experimental days, after end of the experimental period the plasma lipid profile and antioxidant enzymes were determined in hepatic tissue. RESULTS: Increase in plasma glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), hepatic LPO and PO levels with decrease in plasma high density lipoprotein cholesterol (HDL-C), insulin, hepatic reduced glutathione (GSH) content and activities of antioxidant enzymes namely, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of CMEEt at a dose of 200mg/kg for 60 days resulted in the prevention of above mentioned abnormalities. CONCLUSION: The results suggest that CMEEt could be beneficial in the treatment of diabetes, characterized by atherogenous lipoprotein profile, aggravated antioxidant status and impaired glucose metabolism and in their prevention.

Antihyperglycemic activity of Catharanthus roseus leaf powder in streptozotocin-induced diabetic rats.

Catharanthus roseus Linn (Apocynaceae), is a traditional medicinal plant used to control diabetes, in various regions of the world. In this study we evaluated the possible antidiabetic and hypolipidemic effect of C. roseus (Catharanthus roseus) leaf powder in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 55 mg/kg body wt) to male Wistar rats. The animals were divided into four groups: Control, control-treated, diabetic, and diabetic-treated group. Diabetic-treated and control-treated rats were treated with C. roseus leaf powder suspension in 2 ml distilled water, orally (100 mg/kg body weight/day/60 days). In diabetic rats (D-group) the plasma glucose was increased and the plasma insulin was decreased gradually. In the diabetic-treated group lowering of plasma glucose and an increase in plasma insulin were observed after 15 days and by the end of the experimental period the plasma glucose had almost reached the normal level, but insulin had not. The significant enhancement in plasma total cholesterol, triglycerides, LDL and VLDL-cholesterol, and the atherogenic index of diabetic rats were normalized in diabetic-treated rats. Decreased hepatic and muscle glycogen content and alterations in the activities of enzymes of glucose metabolism (glycogen phosphorylase, hexokinase, phosphofructokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase), as observed in the diabetic control rats, were prevented with C. roseus administration. Our results demonstrated that C. roseus with its antidiabetic and hypolipidemic properties could be a potential herbal medicine in treating diabetes.