Gulam Mohammed Husain’s research while affiliated with Indian Institute of Technology BHU and other places

Recently, there is a growing interest of research on the relationship of gut-microbiota and neurological disorders. Increasing number of findings suggests the broader role of gut-microbiota in the modulation of various physiological and pathological conditions and it is now well recognized that a bidirectional communication between brain and gut-microbiota is essential to maintain homeostasis. The gut-brain axis includes central nervous system (CNS), the neuroendocrine and neuroimmune systems, autonomic nervous system, enteric nervous system, and intestinal microbiota. Probiotics (i.e., live microorganisms similar to beneficial microorganisms found in the human gut) are reported to modulate a number of disorders including metabolic disorders, behavioral conditions and cognitive functions. This review covers the significance of gut-brain axis in relation to the overall mental well-being. Apart from the recent studies highlighting the importance of gut-brain axis, here we also reviewed the interaction of few herbal medicines with gut-brain axis. Animal studies have indicated that some herbs or their isolated constituents alter the normal gut flora and have prominent effect on behavioral condition such as anxiety depression and cognition. Thus alteration of gut-brain axis by traditional medicines will be a potential strategy for the management of comorbid CNS disorders and gastrointestinal problems.

Recent studies have revealed diverse therapeutically interesting pharmacological properties of a standardized Hypericum perforatum extract (HpE) potentially useful for treatments of patients with metabolic and psychiatric disorders. Consequently, the presented experiments were designed to test usefulness of the extract for the treatment of comorbid conditions of mood disturbances and anxiety in diabetic rats. Type 2 diabetes mellitus was induced in overnight fasted rats by a single i.p. injection of streptozotocin (STZ; 65 mg/kg), 15 min after an i.p. injection of nicotinamide (120 mg/kg). HpE was administered orally (100 and 200 mg/kg b.w..) to diabetic animals for 14 days. Anxiolytic activity was evaluated using open-field exploration test (OFT) and elevated plus maze (EPM) test. Antidepressant activity was assessed using Porsolt's forced swim test (FST). Fasting blood glucose levels in different groups were analyzed on the 14th day. Diabetic rats showed significant increase in anxiety in OFT and EPM compared to non diabetic normal control rats. Diabetic rats treated with HpE have shown significant anxiolytic activity in OFT and EPM test. In FST, immobility period of vehicle treated diabetic rats was significantly increased (p < 0.05) compared to normal control rats. Treatment with HpE significantly decreased (p < 0.001) immobility period compared to vehicle treated diabetic control rats. HpE treatment significantly reduced elevated blood glucose levels in diabetic rats. The presented observations strongly suggest that HpE could be suitable alternative therapeutic option for prevention, as well as treatment, of comorbidities caused by, or associated with, depression, anxiety and diabetes.

Diverse medicinal uses of the perennial herb Hypericum perforatum L. (Clusiaceae) have been known since ages. During the past few decades numerous clinical reports and studies have demon-strated beneficial effects of its hydro-alcoholic extracts for helping patients with mild to moderate-ly severe depressive symptoms. Critical analysis of available information on bioactivities and clinical efficacy of such extracts revealed that their antide-pressant like efficacy and modes of actions cannot be like those of conventionally known synthetic antidepressant, anxiolytic or any other psychoactive drug known to date (1). Although hyperforin was initially identified as quantitatively the major anti-depressant component of such extracts, currently available information on its therapeutically interest-ing bioactivity profile indicates that it could be a pharmacologically interesting molecule potentially useful for treatments of diverse types of disorders other than depression (2). In addition, it cannot be ignored that therapeutically used Hypericum perfo-ratum extracts contain numerous other bioactive components with diverse spectrums of pharmaco-logical activity profiles. Our earlier studies have shown the efficacy of HpE in variety of CNS disorders including anxiety and depression in non-diabetic rodents (3ñ5). HpE showed beneficial effect in nicotinamide-streptozo-tocin induced diabetic rats and also inhibited rise in blood glucose level without causing overt hypo-glycemia in oral glucose tolerance test in non-dia-betic rats (6). In view of the observed broad spec-trum of activity profile of Hypericum extracts in ani-mal models, it seems to be a particularly good can-didate for treatment of comorbid disorders involving disturbances of CNS functions and diabetes. Experiments described in this communication were therefore conducted to verify this possibility and to

Hypericum perforatum is known to have diverse medicinal uses for centuries. The antidepressant activity of Hypericum perforatum is widely accepted and proved in both animal and clinical studies. Present study was undertaken to investigate the effect of Hypericum perforatum in a battery of animal models for metabolic disorder. Hypericum is tested for hypolipidemic activity in normal rats, antiobesity activity in high-fat-diet induced obese rats, and fructose-fed rats. Hypericum was orally administered as suspension in 0.3% carboxymethyl cellulose at the doses of 100 and 200 mg/kg body weight for 15 consecutive days. Hypericum significantly lowered total cholesterol and low-density cholesterol in normal rats. Hypericum significantly inhibited weight gain in high-fat-fed rats. In fructose-fed rats, Hypericum normalised the dyslipidemia induced by fructose feeding and improved the insulin sensitivity. Taken together, Hypericum could be the antidepressant therapy of choice for patients suffering from comorbid diabetes and obesity.

The aim of the present study was to evaluate the efficacy of a standardized methanol extract of Quassia amara L. (Family: Simaroubaceae) in nicotinamide–streptozotocin‐induced diabetic rats. Non insulin dependent diabetes mellitus was induced by streptozotocin in rats pre‐treated with nicotinamide. Diabetic rats were treated with oral doses of Quassia amara extract (QaE; 100 and 200 mg/kg) or glibenclamide (10 mg/kg; as standard). QaE and glibenclamide were administered as a suspension in 0.3% carboxy methyl cellulose for 14 days. Control animals received an equal volume of vehicle. Blood samples were collected by retro‐orbital puncture on day 14, 1 h after last treatment. Plasma glucose, insulin and lipid parameters (total cholesterol, LDL‐C, HDL‐C and triglycerides) were measured using commercially available biochemical kits. The oral glucose tolerance test was performed to evaluate the effect of the extract on peripheral glucose utilization in normal rats. Both doses of QaE significantly (p < 0.01) reduced elevated fasting blood glucose levels in diabetic rats. In the oral glucose tolerance test, QaE treatment significantly increased (p < 0.05) the glucose tolerance compared with the vehicle. QaE and glibenclamide, effectively normalized dyslipidemia associated with streptozotocin‐induced diabetes. The findings of the present study indicate that Quassia amara extract may be potentially valuable in the treatment of diabetes and associated dyslipidemia.

The main aim of this study was to test the therapeutic potential of a standardized Hypericum perforatum extract in treating metabolic disturbances commonly associated with type-2 diabetes mellitus. Daily oral administration of the Hypericum perforatum extract (100, 200, and 300 mg/kg/day) for 14 consecutive days counteracted in a dose-dependent manner the alterations in blood glucose levels and lipid profile as well as liver glycogen content and body weight changes observed in a rat mode of nicotinamide-streptozotocin-induced diabetes. In general, effects of the highest dose of the extract in this model were quite similar, but not identical, to those of a 10 mg/kg/day dose of glibenclamide. The effects of single oral doses of the extract in a rat oral glucose tolerance test conducted in fasted animals were also analogous to those of an antidiabetic drug therapeutic use. These observations not only further expand the therapeutic potentials of Hypericum extracts but also indicate that stimulation of insulin release could be involved in their modes of actions. The importance of an extract with diverse, therapeutically interesting pharmacological properties is also briefly discussed.

The main aim of this study was to test the therapeutic potential of a standardized Hypericum perforatum extract in treating metabolic disturbances commonly associated with type-2 diabetes mellitus. Daily oral administration of the Hypericum perforatum extract (100, 200, and 300 mg/kg/day) for 14 consecutive days counteracted in a dose-dependent manner the alterations in blood glucose levels and lipid profile as well as liver glycogen content and body weight changes observed in a rat mode of nicotinamide-streptozotocin-induced diabetes. In general, effects of the highest dose of the extract in this model were quite similar, but not identical, to those of a 10 mg/kg/day dose of glibenclamide. The effects of single oral doses of the extract in a rat oral glucose tolerance test conducted in fasted animals were also analogous to those of an antidiabetic drug therapeutic use. These observations not only further expand the therapeutic potentials of Hypericum extracts but also indicate that stimulation of insulin release could be involved in their modes of actions. The importance of an extract with diverse, therapeutically interesting pharmacological properties is also briefly discussed.

The aim of present study was to investigate the in vivo antiaggressive activity of hyperforin using defensive and offensive behavioral models in rodents. Adult male rats and mice were used for the present study. Animals were divided into three groups, with 6 animals in each. Lorazepam was used as standard antiaggressive agent. Animals were treated once daily, for seven consecutive days. Hyperforin (10 mg/kg, i.p.) was injected in a volume of 10 mL/kg for seven consecutive days. Standard group was treated with lorazepam (2.5 mg/kg, i.p.). The control group was treated with equal volume of vehicle (0.3% carboxy methyl cellulose suspension, i.p.). Animals were screened for aggressive behavior before dividing them into groups. At the end of 7 days, experiments were performed. Antiaggressive activity was evaluated using following validated models of aggression viz. foot shock-induced aggression, isolation-induced aggression, resident-intruder aggression and water competition test. Hyperforin treatment significantly (p < 0.001) reduced various aggressive parameters viz. latency to first attack and number of fights in isolation induced aggression, resident intruder aggression and foot shock induced aggression tests. In water competition test, hyperforin treatment significantly (p < 0.001) reduced the duration of water consumption and frequency of water spout possession. We conclude that hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is thus responsible for the antiaggressive activity, suggesting the therapeutic potential of hyperforin as an antiaggressive agent.

The present study was undertaken to investigate the effect of standardized aqueous extract of Picrorhiza kurroa Royle ex Benth. on diabetes. Diabetes mellitus was induced with streptozotocinnicotinamide and rats found diabetic were orally administered standardized aqueous extract of Picrorhiza kurroa (100 and 200 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) or vehicle (0.3% carboxy methyl cellulose suspension) for 14 days. Fasting blood glucose levels and lipid profiles were measured in control as well as diabetic rats after two week treatment. In addition, liver glycogen level of Picrorhiza kurroa extract (PkE) treated diabetic rats were compared to that of control and diabetic control rats. Oral glucose tolerance test was also performed on nondiabetic normal rats. Statistical analyses were performed by one way analysis of variance followed by Tukey-Kramer multiple comparisons test. PkE treatment induced significant reduction (p < 0.001) in elevated fasting blood glucose level in streptozotocinnicotinamide induced type-2 diabetic rats. In oral glucose tolerance test, oral administration of PkE increased the glucose tolerance. PkE treatment also significantly (p < 0.001) reversed the weight loss associated with streptozotocin treatment. These findings provide in vivo evidence that standardized extract of Picrorhiza kurroa possess significant antidiabetic activity in streptozotocin-nicotinamide induced type-2 diabetes mellitus in rats.

The aim of present study was to investigate the in vivo antiaggressive activity of hyperforin using defensive and offensive behavioral models in rodents. Adult male rats and mice were used for the present study. Animals were divided into three groups, with 6 animals in each. Lorazepam was used as standard antiaggressive agent. Animals were treated once daily, for seven consecutive days. Hyperforin (10 mg/kg, i.p.) was injected in a volume of 10 mL/kg for seven consecutive days. Standard group was treated with lorazepam (2.5 mg/kg, i.p.). The control group was treated with equal volume of vehicle (0.3% carboxy methyl cellulose suspension, i.p.). Animals were screened for aggressive behavior before dividing them into groups. At the end of 7 days, experiments were performed. Antiaggressive activity was evaluated using following validated models of aggression viz. foot shock-induced aggression, isolation-induced aggression, resident-intruder aggression and water competition test. Hyperforin treatment significantly (p < 0.001) reduced various aggressive parameters viz. latency to first attack and number of fights in isolation induced aggression, resident intruder aggression and foot shock induced aggression tests. In water competition test, hyperforin treatment significantly (p < 0.001) reduced the duration of water consumption and frequency of water spout possession. We conclude that hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is thus responsible for the antiaggressive activity, suggesting the therapeutic potential of hyperforin as an antiaggressive agent.