Pharmacodynamic interaction of cumin seeds (Cuminum cyminum L.) with glyburide in diabetes.

Background and objective The plethora of anti-diabetic agents available today has many side effects, especially on chronic usage. Hence, alternative approaches utilizing natural and synthetic agents are sought after. Cumin has been shown to be beneficial in treating diabetes. This study evaluates the anti-diabetic effect of cumin and glyburide in the streptozotocin induced diabetes model in rats, and investigates their pharmacodynamic interactions and its implication in diabetes. Methodology The phytoconstituents present in the ethanolic cumin seed extract were determined using appropriate analytical methods. After acute toxicity studies (OECD 2001), the anti-diabetic effect of the extract was evaluated in wistar rats. The rats were divided into five groups - Groups I and II served as the normal and diabetic control. Group III was the standard control (glyburide 5 mg/kg), while groups IV and V received the extract (600 mg/kg) and a combination of the extract (600 mg/kg) and glyburide (2.5 mg/kg; half dose). Biochemical parameters viz. plasma glucose and glycosylated haemoglobin, were measured periodically during the 28 day treatment. On the 28th day, oral glucose tolerance test, lipid profile, renal profile and histopathological evaluation were performed after completion of the study. To investigate the nature of herb-drug interaction, HPLC analysis for estimation of glyburide concentration in the blood was conducted. Results Acute toxicity studies showed the extract to be safe till a dose of 2 g/kg. The extract alone, and in combination with glyburide (half-dose), significantly lowered elevated glucose (by more than 45% from baseline; without producing hypoglycemia), and other lipid and renal parameters. The effects produced by 2.5 mg/kg glyburide, and 5 mg/kg glyburide (without extract) were similar. Histopathological analysis also showed that the extract was able to reverse the degeneration brought about by streptozotocin which was especially notable on the pancreatic and renal tissue. HPLC analysis revealed differing pharmacokinetics of glyburide in the groups treated with 5 mg/kg dose, and 2.5 mg/kg + 600 mg/kg extract. Conclusion The results obtained in this study suggest that Cuminum cyminum L. is a promising anti-diabetic agent, and exhibits pharmacodynamic interaction with glyburide to mitigate symptoms of diabetes mellitus.

A nutraceutical combination of Cinnamomum cassia &Nigella sativa for Type 1 diabetes mellitus.

BACKGROUND: Nigella sativa (black cumin) and Cinnamomum cassia (Cinnamon) are an integral part of the Indian diet, and have also been sourced in the ayurveda, the traditional Indian system of medicine, for their medicinal properties. Both the herbs individually have been successfully evaluated for their preliminary antidiabetic potential. OBJECTIVE: Herein, we dived deeper into antidiabetic properties of these herbs, by investigating the combinatorial effect of both herbs, on parameters of diabetes and further, as an adjunct to metformin therapy, for assessing the pharmacodynamics of herb-drug interaction in diabetes mellitus. The objectives were to screen the combinatorial extract of Nigella sativa & Cinnamomum cassia's (NSCCe) alone and in combination with metformin for its potential in mitigating symptoms of diabetes mellitus-alone, and as an adjunct therapy with metformin. MATERIALS AND METHODS: Diabetes was induced in the animals by a single intraperitoneal injection of streptozotocin. Animals were divided into seven groups with 6 animals each: Vehicle control, Negative control, Positive control (Metformin 50 mg/kg), treatment groups 4 and 5 received NSCCe at the doses of 100 mg/kg and 200 mg/kg, respectively. Groups 6 and 7 received the same doses, in combination with Metformin (50 and 25 mg/kg). Following a 28-day dosing period, plasma glucose levels, lipid profile and renal function profile were evaluated. Histopathological examinations were performed to measure any morphological change in kidney, liver and pancreatic tissue. RESULTS: Combination of Nigella sativa & Cinnamomum cassia extracts significantly normalized plasma glucose levels, lipid profile and kidney function parameters, compared to the diabetic control group. Animals treated with the combinatorial extract and metformin showed more prominent effects on these parameters. Significant reversal in the pancreatic cell damage was observed on treatment with NSCCe. CONCLUSION: This study generates evidence to support Nigella sativa & Cinnamomum cassia as an adjunctive in diabetes treatment protocols.

Influence of piperine and quercetin on antidiabetic potential of curcumin.

BACKGROUND: Curcumin is a nutraceutical obtained from the rhizomes of Curcuma longa with a significant medicinal value against numerous disorders. However, the potential cannot be completely exploited due to low in vivo bioavailability. Hence, in order to enhance the bioavailability of curcumin, we combined it with the bioavailability enhancers like piperine and quercetin. METHODS: The present study was targeted to explore the antidiabetic potential of combinatorial extract of curcumin with piperine and quercetin (CPQ) in streptozotocin- and nicotinamide-induced diabetic rats. Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin (55 mg/kg) and nicotinamide (120 mg/kg-1). CPQ was orally administered at 100 mg kg-1 dose/day for a period of 28 days. At the end of 28 days, blood was analyzed for glucose, high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol level. Oral glucose tolerance test (OGTT) was also conducted at the end of 28 days. RESULTS: Oral administration of CPQ at the dose of 100 mg kg-1 significantly (p<0.01) reduced plasma glucose at the end of 28 days, as compared to the diabetic control group. The reduction in the plasma glucose produced by the CPQ extract was equivalent to that of glibenclamide and significantly more compared to curcumin alone (p<0.01). Furthermore, a significant (p<0.01) reduction in the raised LDL, cholesterol and triglycerides and improvement was observed in the group fed with CPQ compared to diabetic control as well as the alone (p<0.05) curcumin group. There was a significant improvement in the body weight with CPQ compared to diabetes control group. OGTT revealed a significantly high glucose tolerance in CPQ fed rats compared to the diabetic control as well as the rats fed with curcumin alone. CONCLUSIONS: Treatment with combinatorial extract of curcumin presented a significantly better therapeutic potential when compared with curcumin alone, which reveals that CPQ, with reduced dose of curcumin may serve as a therapeutic agent in the treatment of type 2 diabetes mellitus.

Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine.

BACKGROUND: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. OBJECTIVE: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. MATERIALS AND METHODS: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). RESULTS: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs. CONCLUSION: The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential.