Neuroprotective role of Tinospora cordifolia extract in streptozotocin induced neuropathic pain

Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.

Cerebroprotective Actions of Triticum aestivum Linn Powder and Bauhinia purpurea Flower Powder in Surgically Induced Cerebral Infraction in Rats.

OBJECTIVE: The prime objective of this study is to evaluate the cerebroprotective actions of Triticum aestivum (wheatgrass) powder and Bauhinia purpurea flower (dev kanchan) powder against the experimentally induced global ischemia reperfusion injury in rats. MATERIALS AND METHODS: In the first phase of the studies, 1 h before the surgical procedure, the Wistar rats were orally served with varied doses of wheatgrass powder (5, 10, 30, and 100 µg/kg) and Bauhinia flower powder (30, 100, 200, and 300 µg/kg), respectively. The ischemia was induced by 30-min bilateral carotid artery occlusion in succession to reperfusion for 4 h. It was proved that the wheatgrass powder and Bauhinia flower powder yielded a significant, dose-dependent cerebroprotection in terms of reduction in cerebral infarct size when compared with the control group. Coming to the second phase of the studies, a certain potential dose of 10 µg/kg of wheatgrass and 200 µg/kg of Bauhinia flower powders was selected keeping the protective action in view, and the animals were treated for 15 days. RESULTS: The major findings of the study are that wheatgrass and Bauhinia flower powders significantly augmented the magnitude of the antioxidant enzymes, viz., super oxide dismutase and catalase, and further reduced the levels of lipid peroxidation. CONCLUSIONS: The present study clearly showed that the wheatgrass powder and Bauhinia flower powder possess significant antioxidant properties that may act as a key ingredient in various ayurvedic preparations for the treatment of various diseases like cerebral ischemic reperfusion injury. SUMMARY: The wheat grass contains high amount of bioflavonoids, alkaloids, SOD etc which are responsible for anti oxidant activity.The Bauhinia purpurea contains glycosides, flavonoids and also plays a major role in DPPH activity which is responsible for anti oxidant activity.The wheat grass (10 mg/kg) and bauhinia (200 mg/kg) significantly(P < 0.0001) reduced the percentage of infract size when compared to Ischemia reperfusion control group.The wheat grass (10 mg/kg) and bauhinia (200 mg/kg) significantly (P <0.0001) reduced the lipid peroxidation (MDA) and increased SOD and Catalase. Abbreviations used: BCAO: Bilateral Carotid Artery Occlusion, MCA: middle cerebral artery, ROS: reactive oxygen species, SCMC: Sodium carboxy methyl cellulose, p.o: Per oral route, T.T.C: Triphenyl tetrazolium chloride, MDA: Malondialdehyde, SOD: Super oxide dismutase.

Effect of wheat grass powder on aluminum induced Alzheimer's disease in Wistar rats

OBJECTIVE@#To find out the effect of wheat grass on aluminum induced Alzheimer's disease in Wistar rats.@*METHODS@#Memory impairment was induced by aluminum chloride (4.2 mg/kg, i.p.) for 28 d. Memory function was assessed by Morris water maze test. To study the activity of wheat grass (100 mg/kg, p.o.), Wistar rats were administered it for 28 d along with aluminum chloride. Biochemical parameters of oxidative stress were estimated in brain after the treatment.@*RESULTS@#The major finding of this study is that aluminum enhanced oxidative stress. Wheat grass showed a significant improvement in reduction of this oxidative stress by reduction of malondialdehyde levels and enhancement of superoxide dismutase and catalase levels.@*CONCLUSIONS@#The present study clearly demonstrated the beneficial effects of wheat grass that shows good antioxidant properties, and this remarkable effect of wheat grass may act as a key to treat Alzheimer's disease.

Effect of wheat grass powder on aluminum induced Alzheimer's disease in Wistar rats

Objective: To find out the effect of wheat grass on aluminum induced Alzheimer's disease in Wistar rats. Methods: Memory impairment was induced by aluminum chloride (4.2 mg/kg, i.p.) for 28 d. Memory function was assessed by Morris water maze test. To study the activity of wheat grass (100 mg/kg, p.o.), Wistar rats were administered it for 28 d along with aluminum chloride. Biochemical parameters of oxidative stress were estimated in brain after the treatment. Results: The major finding of this study is that aluminum enhanced oxidative stress. Wheat grass showed a significant improvement in reduction of this oxidative stress by reduction of malondialdehyde levels and enhancement of superoxide dismutase and catalase levels. Conclusions: The present study clearly demonstrated the beneficial effects of wheat grass that shows good antioxidant properties, and this remarkable effect of wheat grass may act as a key to treat Alzheimer's disease.

Cardioprotective activity of chalcones in ischemia/reperfusion-induced myocardial infarction in albino rats.

BACKGROUND: There is a comprehensive body of experimental and clinical evidence suggesting that exogenous supplementation of natural antioxidants or augmentation of endogenous antioxidants attenuates the damage caused by myocardial infarction. OBJECTIVE: To evaluate the cardioprotective effects of Cl-chalcone and F-chalcone against ischemia/reperfusion (I/R)-induced myocardial infarction in rats. METHODS: Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. Malondialdehyde was measured in serum and heart tissue, and superoxide dismutase and catalase in heart tissue were measured spectrophotometrically. RESULTS: I/R resulted in significant cardiac necrosis, indicated by a rise in the end products of myocardial lipid peroxidation (malondialdehydes). A loss of antioxidative enzymes (superoxide dismutase and catalase) in heart tissue was also observed in animals subjected to in vivo myocardial I/R injury. DISCUSSION: The present study demonstrated that treatment with Cl-chalcone and F-chalcone significantly limited infarct size, partially but significantly attenuated the level of lipid peroxidation and moderated the loss of antioxidant reserves in rats subjected to 30 min coronary artery occlusion followed by a 4 h reperfusion in comparison with I/R groups. CONCLUSIONS: The results of the present study suggest that chalcones have cardioprotective activity against I/R-induced myocardial infarction in rats.

Protective Effect of Rutin and Naringin on Sperm Quality in Streptozotocin (STZ) Induced Type 1 Diabetic Rats.

Oxidative stress is one of the important causes of the type 1 diabetes induced changes in the sperm quality. Bioflavonoids, Rutin 10 mg/Kg and Naringin 10 mg/Kg were evaluated for their protective effects on sperm parameters, oxidative stress, and histopathology of type 1 diabetic rats. Results demonstrated the reduction in sperm count, sperm motility and vitality in diabetic rats. Mass drug administration (MDA) levels were increased and superoxide dismutase (SOD) catalase levels were decreased. Histopathological changes were evident and in accordance with the above results. In the treatment groups, both Rutin and Naringin in combination with insulin treatment in diabetic rats produced protection from diabetes and improved all the sperm parameters, decreased the MDA levels and increased the SOD and catalase levels. Protection was evident in histological examination. Our data suggests that the possible protection of testicular tissue and reproduction from oxidative stress have been induced by type 1 diabetes mellitus.

Cardioprotective actions of two bioflavonoids, quercetin and rutin, in experimental myocardial infarction in both normal and streptozotocin-induced type I diabetic rats.

OBJECTIVES: Revascularization therapy is the mainstay of treatment in the management of myocardial infarction in normal and diabetic patients. We attempted to evaluate the cardioprotective actions of quercetin and rutin in ischaemia-reperfusion-induced myocardial infarction in both normal and diabetic rats. METHODS: Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazoliumchloride. Serum and tissue malondialdehyde levels and superoxide dismutase and catalase in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. KEY FINDINGS: Results demonstrated the larger infarct size, enhanced lipid peroxidation, partial depletion of antioxidant enzymes and drastic drop in heart rate in diabetic hearts subjected to in-vivo ischaemia-reperfusion in comparison to normal rats subjected to ischaemia-reperfusion. Furthermore, quercetin and rutin significantly limit the infarct size in both normal and diabetic animals in a similar fashion. However, rutin offered complete cardioprotection at a dose of 10 mg/kg in terms of limiting infarct size. Both flavonoids could partially but significantly attenuate the lipid peroxidation. In addition, treatment has shown moderate improvement in heart rate in both normal and diabetic rats. CONCLUSIONS: Our data suggest the possible cardioprotective effects of quercetin and rutin in ischaemia-reperfusion injury in both normal and diabetic rats, and that protection might be in part due to the attenuation of oxidative stress and moderate increment in antioxidant reserves.

Anti-atherosclerotic effect of atorvastatin and clopidogrel alone and in combination in rats.

Atherosclerosis is a disease affecting arterial blood vessels due to the accumulation of macrophage white blood cells and low density lipoproteins. Effects of atorvastatin, a recently introduced lipid lowering statin was studied alone and in combination with clopidogrel in high fat diet fed atherosclerotic rats orally. Results showed significant reduction in total serum cholesterol and malondialdehyde levels and significant improvement in urine creatinine levels. Aortic cross sections of rats treated with clopidogrel alone showed reversal of atherosclerotic calcification. The same effect was observed with the combined treatment of clopidogrel and atorvastatin. Only atorvastatin treatment did not show any histological atheroprotective effect. Atorvastatin and clopidogrel alone and in combination have offered significant atheroprotective effect. No specific advantage was seen with combined treatment of atorvastatin and clopidogrel, moreover the advantages seen with independent drug administration also reduced with combined treatment.

Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats.

BACKGROUND: Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. OBJECTIVES: To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. METHODS: Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. RESULTS: Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. CONCLUSIONS: The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.

The influence of sulindac on diabetic cardiomyopathy: a non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats.

The aim of the present study was to investigate the cardioprotective activity of sulindac as an aldose reductase inhibitor in the development of cardiomyopathy by non-invasive techniques; M-mode and Doppler echocardiography. Diabetes was induced by streptozotocin (45 mg/kg, iv) in the Sprague-Dawley rats. Echocardiography, biochemical and histological studies were carried out in normal control, diabetic untreated, diabetic vehicle (sodium carboxy methyl cellulose, 1%, po) and sulindac (6 mg/kg and 20 mg/kg, po) treated animals at varying time intervals. In the diabetic untreated and vehicle treated rats at 12 weeks after induction of diabetes, there was a significant decrease in the E-wave, an increase in the A-wave and corresponding decrease in the E/A ratio was observed. Significant decrease in the Eat was found after 12 weeks (P < 0.05). Whereas systolic function variables; ejection fraction and fractional shortening were significantly decreased (P < 0.05) after 12 weeks compared to their baseline data. In the sulindac treated animals, there were no significant alterations in the systolic and diastolic parameters were found throughout the study period. Myocardial fructose levels were significantly increased in the diabetic untreated animals compared to normal control rats (P < 0.05), whereas these were significantly decreased in the sulindac (6 mg/kg and 20 mg/kg) treated animals (301.11+/-37.98, 214.11+/-25.31, vs. 914.88+/-56.01 nmol/g) compared to diabetic vehicle treated group (P < 0.05). Extensive focal ischemic myocyte degeneration was observed in the diabetic untreated and vehicle treated rats, whereas in the sulindac (6 mg/kg) treated rats, minimal necrosis was found, with no evidence of necrosis in sulindac (20 mg/kg) group. Our results show for the first time that sulindac has a cardioprotective activity as this agent prevented the development of left ventricular dysfunction in STZ-induced diabetic rats in the 12-week chronic study.

Partial reversal by rutin and quercetin of impaired cardiac function in streptozotocin-induced diabetic rats.

The present investigation was carried out to evaluate the effects of the cyclodextrin complexes quercetin and rutin on left ventricle dysfunction in streptozotocin-induced diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg body mass, i.v.) in Sprague-Dawley rats. Echocardiography and biochemical and histological studies were carried out under normal control, diabetic untreated, normal and diabetic vehicle (beta-cyclodextrin, p.o.), quercetin- (100 and 300 mg/kg, p.o.), and rutin- (100 and 300 mg/kg, p.o.) treated normal and diabetic animals at varying time intervals (1 and 12 weeks). The increase in the serum triglycerides and cholesterol levels was attenuated in the cyclo dextrin complexes of rutin-treated animals significantly more than in the quercetin-treated and diabetic vehicle-treated animals. Left ventricular diastolic dysfunction was observed in diabetic vehicle-treated animals after 12 weeks of the study as determined by a significant decrease in E-wave (45.91%), an increase in the A-wave (75.55%), and a decrease in the E/A ratio (70.14%). However, the percent decrease (after 12 weeks) in the E-wave, increase in the A-wave, and decrease in the E/A ratio were less in the cyclodextrin complexes of rutin-treated animals (100 and 300 mg/kg), which had the following values: E-wave, 12.22% and 13.80%; A-wave, 25.90% and 10.40%; and E/A ratio, 31.01% and 20.52%. In the quercetin-treated animals (100 and 300 mg/kg), which had the following values: E-wave, 40.44% and 36.44%; A-wave, 52.98% and 29.28%; and E/A ratio, 61.70% and 51.11%. Histopathological studies revealed that the degree of myocardial necrosis was less in rutin-treated animals compared with quercetin and diabetic vehicle-treated animals: rutin < quercetin < beta-cyclodextrin. Myocardial fructose levels were significantly increased in the diabetic vehicle-treated animals after 12 weeks of the study, suggesting an increment in the myocardial polyol pathway activity. However, myocardial fructose levels were significantly decreased in the rutin- and quercetin-treated animals compared with the vehicle-treated animals, possibly owing to their aldose reductase inhibitory activity. Quercetin and rutin treatment did not influence the echocardiographical and histo logical parameters in normal animals. Results from the present investigation demonstrated that rutin has a cardioprotective activity, and we conclude that the observed cardioprotection with rutin may be due to its aldose reductase inhibitory activity, as the enhanced aldose reductase pathway is implicated in the development of left ventricle dysfunction by several studies.