Ajit Kumar Thakur

Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata)

Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (穿心蓮 chuān xīn lián), a well-known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress-induced thermoregulatory and other physiological responses in mice. A stress-induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive days, and treatment effects on body weight changes, basal rectal temperature, and foot-shock-triggered hyperthermic responses were quantified on Day 1, Day 5, Day 7, and Day 10 of the experiments. Pentobarbital-induced hypnosis was quantified on the 11th day of treatment. Observations made during a pilot dose finding experiment revealed that, like A. paniculata extracts, pure andrographolide also possess adaptogenic properties. Observed dose-dependent efficacies of 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d andrographolide in the pilot experiment were reconfirmed by conducting two further analogous experiments using separate groups of either male or female mice. In these confirmatory experiments, efficacies of andrographolide were compared with that of 5 mg/kg/d oral doses of the standard anxiolytic diazepam. Significantly reduced body weights and elevated core temperatures of the three vehicle-treated control groups observed on the 5th day and subsequent observational days were completely absent even in the groups treated with the lowest andrographolide dose (3 mg/kg/d) or diazepam (5 mg/kg/d). Benzodiazepine-like potentiation of pentobarbital hypnosis was observed in andrographolide-treated animals. These observations reveal that andrographolide is functionally a diazepam-like desensitizer of biological mechanisms, and processes involved in stress trigger thermoregulatory and other physiological responses.

Beneficial effects of Brassica juncea on cognitive functions in rats.

Abstract Context. Brassica juncea (BJ; Linnaeus) Czern & Coss (Brassicaceae), commonly known as Indian mustard, are enriched in redox-active polyphenols with antidiabetic activities. Diverse other health benefits of this edible plant have been described in classical Ayurvedic texts. Objective: The reported experiments were designed to assess therapeutic potential of a methanol extract of BJ leaves for treatment of cognitive disorders associated with diabetes or caused by central cholinergic dysfunctions. Materials and methods: Elevated plus-maze and active- and passive-avoidance tests were used to assess anti-amnesic potentials of BJ (100, 200 and 400 mg/kg/day, p.o., for 10 days) in alloxan diabetic or scopolamine-challenged rats. Treatment effects on brain acetylcholinesterase (AChE), superoxide dismutase (SOD) and catalase (CAT) activities were quantified in behavioral tested animals. Results: Anti-amnesic efficacy of all three tested BJ doses against scopolamine-induced amnesia was almost equal in all behavioral tests. Such efficacy of the extract in diabetic rats was increased always with its increasing doses. All treatments of BJ dose dependently decreased the elevated level of AChE, and significantly increased the SOD and CAT levels in brain homogenates of scopolamine-challenged and diabetic rats. Minimal effective oral daily doses of BJ in all tests were 100 mg/kg/day for 10 consecutive days. Discussion and conclusion: Our observation indicates that BJ could be a therapeutic option for treatment of cognitive disorders associated with diabetes, or caused by cholinergic deficit and brain oxidative status. They also indicate that the bioactive constituents or mode of actions involved in observed effects of the extract in scopolamine-challenged or diabetic rats are most probably not the same.

Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats.

Abstract Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted.

Therapeutic Targets for Diabetes Mellitus: An Update

Diabetes mellitus is a common form of metabolic disorder where level of blood glucose in the bloodstream raises high, because of deficiency of insulin and development of insulin resistance in diabetic individuals. It is categorize under modern age life style disorder, commonly affected by middle-aged people and the children in adolescents in most developed countries. Diabetic patients develop serious complication with the development of disease, such as obesity, risk of stroke and heart failure. The worldwide prevalence of diabetes is likely to increase from 382 million people in 2013 to 592 million by 2035. Globally antidiabetic drugs formulate the second-largest market by sales in the pharmaceuticals industry after cancer. Various novel targets have identified and recently various therapeutic leads successfully completed their different phases of clinical trials such as GLP-1 agonist, DPP-IV inhibitors, SGLT2 inhibitors, and are going to be the next generation therapy for management of diabetes. Presently the information was collects from PubMed, Science Direct, SciFinder and Google Scholar. In this review, we spotlighted on some common therapeutic targets involved in type 2 diabetes, offering a new concept for developing new drug candidates to produce newer generation antidiabetic drugs against type 2 diabetes.

Antidepressant-like Activity of Andrographis paniculata in Type-2 Diabetic Rats

Pharmacological observations suggesting antidepressants-like efficacy of a medicinally used Andrographis paniculata extract (AP) in type-2 diabetic are presented in this communication. Efficacies of 10 daily oral doses of 50, 100 and 200 mg/kg/day AP and 15 mg/kg/day imipramine were compared in behavioral despair and learned helplessness tests using type-2 diabetic rats, and bio- and neuro-chemical alterations in the brain tissue of treated animals subjected to learned helplessness test were quantified. Significant imipramine like antidepressant activity of AP was observed even after its lowest daily tested (50 mg/kg/day) in both behavioral tests used, and such efficacy of the extract dose dependently increased with its increasing dose. Imipramine like effects of AP in elevating lower hippocampal levels of norepinephrine, dopamine, and serotonin observed in diabetic rats towards normal values were also observed after its 50 mg/kg/day doses and such efficacy of the extract increased also with its increasing daily doses. Levels of all the three monoamines quantified in 100 mg/kg/day AP treated diabetic rats were significantly higher than those of the non-diabetic animals. Imipramine had no significant effects on body weight losses, hyperglycemia, insulin deficiency, lower catalase and superoxide dismutase activities and higher lipid peroxides in the frontal cortex, and mitochondrial monoamine oxidase activities observed in diabetic animals. All such quantified biochemical and other pathologies observed in diabetic were significantly antagonized even by 50 mg/kg daily oral doses of AP, and its efficacies always increased with its increasing daily doses. These observations strongly suggest that AP could be an herbal alternative for treatments of diabesity-associated depression resistant to imipramine like antidepressants, and that antidepressants like efficacy of the extract is most probably due to its inhibitory effects on brain mitochondrial monoamine oxidase activities. The observed beneficial of AP on brain oxidative status could be indicative of its neuro-protective potentials as well. In any case its minimal effective doses for all such efficacies should be below or around 50 mg/kg/day.

Obesity, Cancer and Psychopathology: Can Vegetarian Diet Be of Help?

High body mass index, low fruit and vegetable intake, physical inactivity, tobacco use, alcohol use and unsafe sex are six behaviorally modifiable risk factors potentially involved in increased cancer rates observed during recent years. Numerous epidemiological and experimental data are now beginning to point out that the functions of the central nervous system may also be detrimentally effected by these risk factors, and that complex psychobiological processes are involved in obesity associated comorbidities. Several phytochemicals commonly consumed with fruits and vegetables are known since long to possess chemopreventive as well as beneficial effects on cognitive functions. However, as yet little concentrated efforts have been made to properly understand the health benefits of diverse combinations of phytochemicals commonly consumed with every day meals. Available information on health benefits of some vegetables in obesity associated carcinogenesis are summarized and discussed in short in this chapter. It is concluded that at old fashioned holistic pharmacological approaches could be helpful for identifying effective safe and affordable nutraceuticals and drug leads urgently needed for combating oncological problems associated with obesity.

Perspective of Andrographis paniculata in Neurological Disorders

Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) is a labdane diterpinoids rich medicinal plant. Andrographolide is quantitatively the major bioactive secondary metabolite present in this herb. In Ayurveda, Andrographis paniculata is classified as a Rasayana herb. Several pre-clinical and well-controlled clinical trials performed during recent years have confirmed the therapeutic efficacies and broad safety profile of Andrographis paniculata as well as its secondary metabolites. Therefore, Andrographis paniculata seems to be another example of medicinal Ayurvedic plants which could not only be better explored for discovering structurally and functionally novel therapeutic leads, but also for identifying novel pharmacological principles and targets potentially useful for neurological disorders.