Current Research: Ashwagandha

Here's some current research and helpful links on Cognitive-Emotional research involving Ashwagandha (Withania somnifera)

Ashwagandha (Withania somniferea) -Neha.Vindhya

Integrated approach to management of Parkinson's"  http://online.liebertpub.com/doi/pdfplus/10.1089/act.2011.17308

CITATIONS

Sehgal, N., A. Gupta, et al. (2012). "Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver." Proc Natl Acad Sci U S A 109(9): 3510-3515.

A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of beta-amyloid peptides (Abeta) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Abeta and a decrease in brain Abeta monomer after 7 d, indicating increased transport of Abeta from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Abeta-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Abeta levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Abeta. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Abeta, indicating that increase in liver LRP and sLRP occurring independent of Abeta concentration could result in clearance of Abeta. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Abeta clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.

Kumar, S., R. J. Harris, et al. (2012). "An aqueous extract of Withania somnifera root inhibits amyloid beta fibril formation in vitro." Phytother Res 26(1): 113-117.

The ability of an aqueous extract of W. somnifera L. Dunal (Family: Solanaceae) roots to inhibit fibril formation by the amyloid-beta peptide in vitro was investigated. W. somnifera is used extensively in traditional Ayurvedic medicine as a nerve tonic with reputed memory enhancing properties. Inhibition of fibrillogenesis measured by transmission electron microscopy and ThT fluorescence assay showed that an aqueous extract of W. somnifera strongly inhibited Abeta fibril formation in a concentration-dependent manner, when compared with control samples. These results suggest that the aqueous extract of W. somnifera root has an ability to inhibit the formation of mature amyloid-beta fibrils in vitro, which are known to lead to amyloid plaque formation in vivo.

Grover, A., A. Shandilya, et al. (2012). "Computational evidence to inhibition of human acetyl cholinesterase by withanolide a for Alzheimer treatment." J Biomol Struct Dyn 29(4): 651-662.

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia. So far only five drugs have been approved by US FDA that temporarily slow worsening of symptoms for about six to twelve months. The limited number of therapeutic options for AD drives the exploration of new drugs. Enhancement of the central cholinergic function by the inhibition of acetylcholinesterase is a prominent clinically effective approach for the treatment of AD. Recently withanolide A, a secondary metabolite from the ayurvedic plant Withania somnifera has shown substantial neuro-protective ability. The present study is an attempt to elucidate the cholinesterase inhibition potential of withanolide A along with the associated binding mechanism. Our docking simulation results predict high binding affinity of the ligand to the receptor. Further, long de novo simulations for 10_ns suggest that ligand interaction with the residues Thr78, Trp81, Ser120 and His442 of human acetylcholinesterase, all of which fall under one or other of the active sites/subsites, could be critical for its inhibitory activity. The study provides evidence for consideration of withanolide A as a valuable small ligand molecule in treatment and prevention of AD associated pathology. The present information could be of high value for computational screening of AD drugs with low toxicity to normal cells. Accurate knowledge of the 3D structure of human acetylcholinesterase would further enhance the potential of such analysis in understanding the molecular interaction basis between ligand and receptor.

Shah, J. and R. Goyal (2011). "Investigation of neuropsychopharmacological effects of a polyherbal formulation on the learning and memory process in rats." J Young Pharm 3(2): 119-124.

OBJECTIVE: To investigate the neuropsychopharmacological effect of a polyherbal formulation (PHF) on the learning and memory processes in rats. MATERIALS AND METHODS: PHF contains Withania somnifera (Ashwagandha), Nardostachys jatamansi (Jatamansi), Rauwolfia serpentina (Sarpagandha), Evolvulus alsinoides (Shankhpushpi), Asparagus racemosus (Shatavari), Emblica officinalis (Amalki), Mucuna pruriens (Kauch bij extract), Hyoscyamus niger (Khurasani Ajmo), Mineral resin (Shilajit), Pearl (Mukta Shukhti Pishti), and coral calcium (Praval pishti). Its effect (500 mg / kg, p.o.) on the learning and memory processes was tested. The activity of PHF on memory acquisition and retention was studied using passive avoidance learning and elevated plus maze model (EPM) in rats. RESULTS: The animals treated with PHF showed a significant decrease in transfer latency as compared to the control group in EPM. PHF also produced significant improvement in passive avoidance acquisition and memory retrieval, as compared to the controls and reduced the latency to reach the shock free zone (SFZ) after 24 hours. CONCLUSION: The PHF produces significant improvement in passive avoidance acquisition and memory retrieval in rats, which needs further investigation.

Ramanathan, M., B. Balaji, et al. (2011). "Behavioural and neurochemical evaluation of Perment an herbal formulation in chronic unpredictable mild stress induced depressive model." Indian J Exp Biol 49(4): 269-275.

Perment, a polyherbal Ayurvedic formulation that contains equal parts of Clitoria ternatea Linn., Withania somnifera Dun., Asparagus racemosus Linn., Bacopa monniera Linn., is used clinically as mood elevators. The aim of the present study was to explore the behavioural effects and to understand possible mode of action of Perment in stress induced depressive model. Chronic unpredictable mild stress (CUMS) was used to induce depression in rats. Open field exploratory behaviour, elevated plus maze, social interaction and behavioural despair tests were used to assess behaviour. Using standard protocols plasma noradrenaline, serotonin, corticosterone and brain/adrenal corticosterone levels were measured to support the behavioural effects of Perment. Exposure to CUMS for 21 days caused anxiety and depression in rats, as indicated by significant decrease in locomotor activity in the open field exploratory behaviour test and increased immobility period in the behavioural despair test. Perment predominantly exhibited antidepressant action than anxiolytic activity. Further Perment increased the plasma noradrenaline and serotonin levels in stressed rats. No significant alteration in the brain corticosterone level in stressed rats was observed with Perment treatment. However the adrenal corticosterone level is decreased with Perment. It can be concluded that the Perment formulation exhibited synergistic activity, has a significant antidepressant and anxiolytic activity, which may be mediated through adrenergic and serotonergic system activation. Currently the formulation is clinically used as anxiolytic but the present results suggest that the formulation can also be indicated in patients affected with depression.

Mohan, L., U. S. Rao, et al. (2011). "Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats." Evid Based Complement Alternat Med 2011.

The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety.

Yadav, C. S., V. Kumar, et al. (2010). "Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: attenuation by Withania somnifera." Indian J Biochem Biophys 47(2): 117-120.

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immunomodulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.

Wollen, K. A. (2010). "Alzheimer's disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners." Altern Med Rev 15(3): 223-244.

Alzheimer's disease (AD) is characterized by dysfunctional intracellular and extracellular biochemical processes that result in neuron death. This article summarizes hypotheses regarding cell dysfunction in AD and discusses the effectiveness of, and problems with, different therapies. Pharmaceutical therapies discussed include cholinesterase inhibitors, memantine, antihypertensive drugs, anti-inflammatory drugs, secretase inhibitors, insulin resistance drugs, etanercept, brain-derived neurotrophic factor, and immunization. Nutritional and botanical therapies included are huperzine A, polyphenols, Ginkgo, Panax ginseng, Withania somnifera, phosphatidylserine, alpha-lipoic acid, omega-3 fatty acids, acetyl L-carnitine, coenzyme Q10, various vitamins and minerals, and melatonin. Stimulatory therapies discussed are physical exercise, cognitive training, music, and socialization. Finally, treatment strategies are discussed in light of the benefits and drawbacks of different therapeutic approaches. It is concluded that potential risks of both approved and non-approved therapies should be weighed against the potential benefits and certain consequences of disease progression. Approaches that target several dysfunctions simultaneously and that emphasize nutritional, botanical, and stimulatory therapies may offer the most benefit at this time.

Ven Murthy, M. R., P. K. Ranjekar, et al. (2010). "Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha." Cent Nerv Syst Agents Med Chem 10(3): 238-246.

Ayurveda is a Sanskrit word, which means "the scripture for longevity". It represents an ancient system of traditional medicine prevalent in India and in several other south Asian countries. It is based on a holistic view of treatment which is believed to cure human diseases through establishment of equilibrium in the different elements of human life, the body, the mind, the intellect and the soul [1]. Ayurveda dates back to the period of the Indus Valley civilization (about 3000 B.C) and has been passed on through generations of oral tradition, like the other four sacred texts (Rigveda, Yajurveda, Samaveda and Atharvanaveda) which were composed between 12(th) and 7(th) century B.C [2, 3]. References to the herbal medicines of Ayurveda are found in all of the other four Vedas, suggesting that Ayurveda predates the other Vedas by at least several centuries. It was already in full practice at the time of Buddha (6(th) century B.C) and had produced two of the greatest physicians of ancient India, Charaka and Shushrutha who composed the basic texts of their trade, the Samhitas. By this time, ayurveda had already developed eight different subspecialties of medical treatment, named Ashtanga, which included surgery, internal medicine, ENT, pediatrics, toxicology, health and longevity, and spiritual healing [4]. Ayurvedic medicine was mainly composed of herbal preparations which were occasionally combined with different levels of other compounds, as supplements [5]. In the Ayurvedic system, the herbs used for medicinal purposes are classed as brain tonics or rejuvenators. Among the plants most often used in Ayurveda are, in the descending order of importance: (a) Ashwagandha, (b) Brahmi, (c) Jatamansi, (d) Jyotishmati, (e) Mandukparni, (f) Shankhapushpi, and (g) Vacha. The general appearance of these seven plants is shown in Fig.1. Their corresponding Latin names, as employed in current scientific literature, the botanical families that each of them belongs to, their normal habitats in different areas of the world, as well as the common synonyms by which they are known, are shown in the Table 1. The scientific investigations concerning the best known and most scientifically investigated of these herbs, Ashwagandha will be discussed in detail in this review. Ashwagandha (Withania somnifera, WS), also commonly known, in different parts of the world, as Indian ginseng, Winter cherry, Ajagandha, Kanaje Hindi and Samm Al Ferakh, is a plant belonging to the Solanaceae family. It is also known in different linguistic areas in India by its local vernacular names [6]. It grows prolifically in dry regions of South Asia, Central Asia and Africa, particularly in India, Pakistan, Bangladesh, Sri Lanka, Afghanistan, South Africa, Egypt, Morocco, Congo and Jordon [7]. In India, it is cultivated, on a commercial scale, in the states of Madhya Pradesh, Uttar Pradesh, Punjab, Gujarat and Rajasthan [6]. In Sanskrit, ashwagandha, the Indian name for WS, means "odor of the horse", probably originating from the odor of its root which resembles that of a sweaty horse. The name"somnifera" in Latin means "sleep-inducer" which probably refers to its extensive use as a remedy against stress from a variety of daily chores. Some herbalists refer to ashwagandha as Indian ginseng, since it is used in India, in a way similar to how ginseng is used in traditional Chinese medicine to treat a large variety of human diseases [8]. Ashwagandha is a shrub whose various parts (berries, leaves and roots) have been used by Ayurvedic practitioners as folk remedies, or as aphrodisiacs and diuretics. The fresh roots are sometimes boiled in milk, in order to leach out undesirable constituents. The berries are sometimes used as a substitute to coagulate milk in cheese making. In Ayurveda, the herbal preparation is referred to as a "rasayana", an elixir that works, in a nonspecific, global fashion, to increase human health and longevity. It is also considered an adaptogen, a nontoxic medication that normalizes physiological functions, disturbed by chronic stress, through correction of imbalances in the neuroendocrine and immune systems [9, 10]. The scientific research that has been carried out on Ashwagandha and other ayurvedic herbal medicines may be classified into three major categories, taking into consideration the endogenous or exogenous phenomena that are known to cause physiological disequilibrium leading to the pathological state; (A) pharmacological and therapeutic effects of extracts, purified compounds or multi-herbal mixtures on specific non-neurological diseases; (B) pharmacological and therapeutic effects of extracts, purified compounds or multi-herbal mixtures on neurodegenerative disorders; and (C) biochemical, physiological and genetic studies on the herbal plants themselves, in order to distinguish between those originating from different habitats, or to improve the known medicinal quality of the indigenous plant. Some of the major points on its use in the treatment of neurodegenerative disorders are described below.

Shah, J. S. and R. K. Goyal (2010). "Usage trends for memory and vitality-enhancing medicines: A pharmacoepidemiological study involving pharmacists of the Gujarat region." Int J Ayurveda Res 1(3): 138-143.

OBJECTIVE: The aim of the study was to explore the trends and rationale of use of memory and vitality-enhancing medicines (MVEM) in the Gujarat region. MATERIALS AND METHODS: A prospective pharmacoepidemiological study involving pharmacists of Gujarat region was carried out in the year 2005. Pharmacists (n = 351) working in general and Ayurvedic medical stores were selected from 12 districts of Gujarat region. The pharmacists were explained about the objective of the study and were given a pretested, validated questionnaire. OUTCOME MEASURES: The questionnaire included the questions regarding herbal MVEM used most commonly, percentage sale of herbal MVEM - sold with or without prescriptions - age group of patients and professional groups who used these drugs most commonly. RESULTS: The number of individuals using MVEM was highest in the age group of 11-20 years (17.54%), followed by the 21-40 years group (17.12%), supporting the results that the professional group of students (17.29%) and the persons of business or service class (15.29%) are the highest users of these medicines. Evaluation of various constituents in the marketed polyherbal MVEM revealed that Brahmi (Bacopa monniera), Shankhpushpi (Evolvulus alsinoides), Ashwangandha (Withania somnifera), Jatamansi (Nardostychos jatamansi), Vacha (Acorus calamus) and Amla (Phyllanthus emblica) were the common ingredients in the polyherbal preparations. CONCLUSIONS: This study highlights commonly used Ayurvedic medicines that can be explored for safely enhancing memory and vitality performance. Hence, detailed and scientifically designed research on these drugs would help to identify safe and effective drugs for enhancing the same.

Gupta, G. L. and A. C. Rana (2007). "Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats." Indian J Physiol Pharmacol 51(4): 345-353.

This study investigated the effect of Withania somnifera Dunal (WS) root extract and diazepam in social isolation induced behavior such as anxiety and depression in rats. Rats were isolated for 6 weeks and the assessment of changed behavior were done on elevated plus maze (EPM) and forced swim test (FST). Isolation reared rats spent less time into the open arms on EPM and significantly increased immobility time in FST compared to group housed rats. WS (100, 200 or 500 mg/kg, oral) and diazepam (1 or 2 mg/kg, ip) dose dependently increased the time spent and entries into the open arms on EPM test and showed the anxiolytic activity. Subeffective dose of WS (50 mg/kg, oral) potentiated the anxiolytic action of diazepam (0.5, 1 or 2 mg/kg, ip). WS (100, 200 or 500 mg/kg, oral) also reduced the immobility time in FST, thus showed antidepressant effect in both group housed and social isolates. The investigations support the use of WS as a mood stabilizer in socially isolation behavior in Ayurveda.

Bhattacharya, S. K., A. Bhattacharya, et al. (2000). "Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study." Phytomedicine 7(6): 463-469.

The roots of Withania somnifera (WS) are used extensively in Ayurveda, the classical Indian system of medicine, and WS is categorized as a rasayana, which are used to promote physical and mental health, to provide defence against disease and adverse environmental factors and to arrest the aging process. WS has been used to stabilize mood in patients with behavioural disturbances. The present study investigated the anxiolytic and antidepressant actions of the bioactive glycowithanolides (WSG), isolated from WS roots, in rats. WSG (20 and 50 mg/kg) was administered orally once daily for 5 days and the results were compared by those elicited by the benzodiazepine lorazepam (0.5 mg/kg, i.p.) for anxiolytic studies, and by the tricyclic anti-depressant, imipramine (10 mg/kg, i.p.), for the antidepressant investigations. Both these standard drugs were administered once, 30 min prior to the tests. WSG induced an anxiolytic effect, comparable to that produced by lorazepam, in the elevated plus-maze, social interaction and feeding latency in an unfamiliar environment, tests. Further, both WSG and lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety, when the levels were increased following administration of the anxiogenic agent, pentylenetetrazole. WSG also exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swim-induced 'behavioural despair' and 'learned helplessness' tests. The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression in Ayurveda.