M. Nazam Ansari

Evaluation of antioxidant and neuroprotective effect of ethanolic extract of Embelia ribes Burm in focal cerebral ischemia/reperfusion-induced oxidative stress in rats.

Antioxidants have been the focus of studies for developing neuroprotective agents to be used in the therapy for stroke, which is an acute and progressive neurodegenerative disorder and is the second leading cause of death throughout the world. In fact, many herbal antioxidants have been developed in in vitro and in vivo experiments and some of these have been tested in clinical studies of stroke. Embelia ribes have been reported to have antioxidant and antidiabetic effects. In addition to these effects, this study was designed to investigate the neuroprotective effect of ethanolic extract of E. ribes Burm fruits on middle cerebral artery occlusion (MCAO)‐induced focal cerebral ischemia in rats. Male Wistar albino rats were fed ethanolic E. ribes extract (100 and 200 mg/kg body weight; p.o.) for 30 days. After 30 days of feeding, all animals were anaesthetized with chloral hydrate (400 mg/kg, i.p.). The right middle cerebral artery was occluded with a 4‐0 suture for 2 h. The suture was removed after 2 h to allow reperfusion injury. Ischemia followed by reperfusion in ischemic group rats significantly (P < 0.001) reduced the grip strength activity and non‐enzymatic (reduced glutathione, GSH) and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione‐S‐transferase (GST)] antioxidant levels in hippocampus and frontal cortex compared to sham‐operated rats. Further, serum lactate dehydrogenase (LDH) and thiobarbituric acid reactive substance (TBARS) levels in hippocampus and frontal cortex were significantly increased in ischemic group compared to sham‐operated rats. Furthermore, ethanolic E. ribes extracts pretreatment significantly (P < 0.001) increased the grip strength activity, and GSH, GPx, GR and GST levels in hippocampus and frontal cortex with significant decrease in LDH levels in serum and TBARS levels in hippocampus and frontal cortex compared to MCAO + vehicle group rats. The data from this study suggest that chronic treatment with ethanolic E. ribes extract enhances the antioxidant defense against MCAO‐ induced focal cerebral ischemia in rats and exhibits neuroprotective activity.

The effect of aqueous extract of Embelia ribes Burm on serum homocysteine, lipids and oxidative enzymes in methionine induced hyperhomocysteinemia

Objective: The present study was designed to evaluate the effect of the aqueous extract of Embelia ribes Burm fruits on methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative stress in albino rats. Materials and Methods: Adult male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days. Hyperhomocysteinemia was induced by methionine treatment (1 g/kg, p.o.) for 30 days and folic acid (100 mg/kg, p.o.) was used as a standard drug. The animals were evaluated for various biochemical parameters in serum and brain homogenates, followed by histopathological studies at the end of the study. Results: Administration of methionine (1 g/kg, p.o.) for 30 days to vehicle control rats produced significant increase (P < 0.01) in homocysteine, lactate dehydrogenase (LDH), total cholesterol, triglycerides, low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) levels in serum and lipid peroxides (LPO) levels in brain homogenates, with reduction in high density lipoprotein (HDL-C) levels in serum, and glutathione (GSH) content in brain homogenates, as compared to vehicle control rats. Administration of the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days, to hyperhomocysteinemic rats, significantly (P < 0.01) decreased the levels of homocysteine, LDH, total cholesterol, triglycerides, LDL-C and VLDL-C and increased the HDL-C levels in serum. In addition, a significant (P < 0.01) decrease in LPO levels with increase in GSH content was observed in hyperhomocysteinemic rats treated with the aqueous extract of Embelia ribes. The results were comparable to those obtained with folic acid, a standard antihyperhomocysteinemic drug. Conclusion: The present results provide clear evidence that the aqueous extract of Embelia ribes treatment enhances the antioxidant defense against methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative stress in brain.

Protective effect of aqueous extract of Embelia ribes Burm fruits in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Objective: The present study was carried out to evaluate the neuroprotective effect of the aqueous extract of Embelia ribes, in focal ischemic brain. Materials and Methods: Adult male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days. After 30 days of feeding, all the animals were anaesthetized with chloral hydrate (400 mg/kg, i.p.). The right middle cerebral artery was occluded with a 4-0 suture for 2 h. The suture was removed after 2 h, to allow reperfusion injury. The animals were used for grip strength measurement, biochemical estimation in serum and brain tissue (hippocampus and frontal cortex) and cerebral infarct size measurement. Results: In the ischemic group, a significant (P < 0.01) alteration in the markers of oxidative damage (thiobarbituric acid reactive substances (TBARS); reduced glutathione (GSH); glutathione peroxidase (GPx); glutathione reductase (GR); and, glutathione-S-transferase (GST)) was observed in the hippocampus and frontal cortex, as compared to sham operated rats. We observed that the animals treated with the aqueous extract of Embelia ribes had a significant (P < 0.01) increase in the poststroke grip strength activity. Further, supplementation with aqueous extract of Embelia ribes reversed the levels/activities of the above mentioned biochemical parameters significantly (P< 0.01) and also resulted in decreased cerebral infarct area, as compared to the ischemic group. Conclusion: The results of our study, for the first time, provide clear evidence that aqueous extract of Embelia ribes pretreatment ameliorates cerebral ischemia/reperfusion injury and enhances the antioxidant defense against middle cerebral artery occlusion-induced cerebral infarction in rats; it exhibits neuroprotective property.

Ameliorative effect of an ethanol extract of Embelia ribes fruits on isoproterenol-induced cardiotoxicity in diabetic rats

The present study explored the protective effect of Embelia ribes Burm. (Myrsinaceae) fruit ethanol extract on isoproterenol (ISO)-induced cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. STZ (40 mg/kg, intravenously, single-injection)-induced diabetic rats had significantly (p < 0.01) increased heart rate (HR), systolic blood pressure (SBP), blood glucose, HbA1C, serum LDH, serum CK, and myocardial TBARS levels, and decreased blood glutathione and myocardial endogenous antioxidants, viz. SOD, CAT, and GSH levels in comparison to group I rats. ISO (5.25 and 8. 5 mg/kg, s.c., for two consecutive days) administration produced myocardial necrosis as evidenced by a significant (p < 0.01) increase in HR, SBP, serum LDH, serum CK, and myocardial TBARS levels and a significant (p < 0.01) decrease in blood glutathione, and myocardial endogenous antioxidant levels in comparison to group I rats. Further, ISO administration to diabetic rats showed a significant (p < 0.01) increase in SBP, blood glucose, and HbA1C levels along with a significant (p < 0.01) decrease in HR, blood glutathione, serum LDH, serum CK, myocardial TBARS, SOD, CAT, and GSH levels as compared to ISO-only treated (i.e. group IV) rats. Forty days treatment of Embelia ribes ethanol extract (200 mg/kg) to pathogenic (STZ + ISO treated) rats resulted in a significant (p < 0.01) increase in HR, blood glutathione, serum LDH, and myocardial endogenous antioxidant levels with a significant (p < 0.01) decrease in SBP, blood glucose, HbA1C, serum CK, and myocardial TBARS levels as compared to pathogenic (STZ + ISO treated) rats. The study demonstrates the ability of Embelia ribes extract to attenuate ISO-induced oxidative stress in diabetic rats, enhancing cellular antioxidant defense.

Effect of Rosuvastatin on Methionine-Induced Hyperhomocysteinaemia and Haematological Changes in Rats

The present study was designed to investigate the protective effect of rosuvastatin on methionine-induced hyperhomocysteinaemia and haematological changes in albino rats. Methionine (1 g/kg, orally) administration to pathogenic control rats (i.e. group II) for 30 days significantly (P < 0.01) increased the levels of homocysteine, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TGs) and decreased the levels of high-density lipoprotein cholesterol (HDL-C) in serum. Haematological observations of the peripheral blood smears of pathogenic rats (i.e. group II) fed with methionine also showed crenation of red blood cells cell membrane and significant (P < 0.01) increase in total leucocyte count, differential leucocyte count and platelet counts with significant (P < 0.01) decrease in the mean haemoglobin levels as compared to vehicle control rats (group I). Administration of rosuvastatin (0.5 mg/kg/day, orally) to hyperhomocysteinaemic rats for 30 days significantly (P < 0.01) decreased the levels of homocysteine, TC, TGs, LDL-C, VLDL-C and increased the levels of HDL-C in serum. The present results provide clear evidence that oral treatment with rosuvastatin produces homocysteine and lipid lowering activity and also reversal of haematological changes induced by methionine in rats.

Effect of an Ethanol Extract of Embelia ribes Fruits on Isoproterenol-Induced Myocardial Infarction in Albino Rats

The ethanol extract of dried fruits of Embelia ribes Burm (Myrsinaceae) was evaluated for protection against isoproterenol (ISO)-induced myocardial infarction in albino rats. The cardiotoxicity induced by ISO (5.25 and 8.5 mg/kg, s.c., for two consecutive days) was indicated by a significant increase (P < 0.01) in heart rate and systolic blood pressure, elevated levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum, with increased thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels in heart homogenates, as compared to normal healthy control rats. Microscopical examination (histopathology) was also performed on the myocardial tissue. Pretreatment with ethanol Embelia ribes extract (200 mg/kg, p.o., 40 days) significantly (P < 0.01) decreased the elevated levels of LDH and CK in serum and myocardial TBARS and increased the reduced levels of GSH, SOD and CAT in heart homogenates in ISO-induced myocardial infarction in albino rats. Histopathological observation revealed a marked protection by the extract in myocardial necrotic damage. The results of our study, for the first time, provide clear evidence that ethanol Embelia ribes extract treatment enhances the antioxidant defense against ISO-induced myocardial infarction in rats and exhibit cardioprotective properties.

Antihyperhomocysteinemic Activity of an Ethanol Extract from Embelia ribes. in Albino Rats

Abstract An ethanol extract from Embelia ribes. Burm (Myrsinaceae) fruits was investigated for its antihyperhomocysteinemic and lipid-lowering potential in methionine-induced hyperhomocysteinemia rats. Hyperhomocysteinemia was induced by methionine (1 g/kg, p.o., 30 days) through drinking water in male albino rats. A significant (p < 0.01) increase in homocysteine, lactate dehydrogenase, total cholesterol, triglycerides, and low-density lipoprotein levels in serum and lipid peroxides levels in heart homogenates with a concomitant decrease in serum high-density lipoprotein and myocardial glutathione levels were observed in pathogenic control rats compared with normal healthy control rats. Furthermore, ethanol Embelia ribes. extract (100 and 200 mg/kg, p.o., 30 days) treatment in both the doses significantly reversed all the above-mentioned parameters compared with pathogenic control rats. The results of test drug were comparable with folic acid (100 mg/kg, p.o.), a standard antihyperhomocysteinemic agent. The results indicated that ethanol Embelia ribes. extract has significant antihyperhomocysteinemic and lipid-lowering potential in hyperhomocysteinemic rats.