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    • Ashwagandha (Withania somnifera; also called Indian ginseng or Winter Cherry) is a medicinal botanical grown in India that is revered for the multiple, health-providing benefits of powders and extracts made from its roots and leaves. It has been used for thousands of years in Ayurvedic medicine as a daily tonic to help treat such psychological and physical ailments as stress, strain, fatigue, cognitive function, exercise recovery, inflammation, immune health, blood sugar balance, and cardiovascular health.
    • In the past decade its use as a dietary supplement has become increasingly popular, particularly in the areas of stress reduction, energy, and mental cognition.
Withania somnifera (Ashwagandha leaf and root extract)

1: Cognition

Pharmacognosy Research, January – March 2014, Volume 6, Issue 1

Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants

Usharani Pingali, Raveendranadh Pilli, Nishat Fatima

Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, India

Abstract

Background: Withania somnifera is an herbal medicine that has been known to possess memory-enhancing properties. The current study involved an assessment of cognitive and psychomotor effects of Withania somnifera extract in healthy human participants.

Materials and Methods: In this prospective, double-blind, multi-dose, placebo-controlled, crossover study, 20 healthy male participants were randomized to receive 250 mg two capsules twice daily of an encapsulated dried aqueous extract of roots and leaves of Withania somnifera or a matching placebo for a period of 14 days. Cognitive and psychomotor performance was assessed pre-dose (day 1) and at 3 hrs post-dose on day 15 using a battery of computerized psychometric tests. After a washout period of 14 days, the subjects crossed-over to receive the other treatment for a further period of 14 days as per prior randomization schedule. Same battery of test procedures were performed to assess cognitive and psychomotor

Results: Significant improvements were observed in reaction times with simple reaction, choice discrimination, digit symbol substitution, digit vigilance, and card sorting tests with Withania somnifera extract compared to placebo. However, no effect can be seen with the finger tapping test.

Conclusion: These results suggest that Withania somnifera extract can improve cognitive and psychomotor performance and may, therefore, be a valuable adjunct in the treatment of diseases associated with cognitive impairment.

2:Cognition

J Clin Psychiatry 74:11, November 2013

Randomized Placebo-Controlled Adjunctive Study of an Extract of Withania somnifera for Cognitive Dysfunction in Bipolar Disorder

K. N. Roy Chengappa, MD, FRCP(C); Christopher R. Bowie, PhD; Patricia J. Schlicht, BSN, MA; David Fleet, BSc, MSc, MSc; Jaspreet S. Brar, MBBS, PhD; and Ripu Jindal, MD

Abstract

Objective: Cognitive impairments contribute significantly to inadequate functional recovery following illness episodes in bipolar disorder, yet data on treatment interventions are sparse. We assessed the cognitive effects of a standardized extract of the medicinal herb Withania somnifera (WSE) in bipolar disorder.

Method: Sixty euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week, double-blind, placebo-controlled, randomized study of WSE (500mg/d) as a procognitive agent added adjunctively to the medications being used as maintenance treatment for bipolar disorder. Study enrollment and data analyses were completed between December 2008 and September 2012. Cognitive testing at baseline and 8 weeks assessed primary efficacy outcomes. Psychopathology and adverse events were monitored at scheduled visits.

Results: Fifty-three patients completed the study (WSE, n = 24; placebo, n = 29), and the 2 groups were matched in terms of demographic, illness, and treatment characteristics. Compared to placebo, WSE provided significant benefits for 3 cognitive tasks: digit span backward (P = .035), Flanker neutral response time (P = .033), and the social cognition response rating of the Penn Emotional Acuity Test (P= .045). The size of the WSE treatment effect for digit span backward was in the medium range (Cohen d = 0.51; 95% CI, 0.25–0.77). None of the other cognitive tasks showed significant between-group differences. Mood and anxiety scale scores remained stable, and adverse events were minor.

Conclusions: Although results are preliminary, WSE appears to improve auditory-verbal working memory (digit span backward), a measure of reaction time, and a measure of social cognition in bipolar disorder. Given the paucity of data for improving cognitive capacity in bipolar disorder, WSE offers promise, appears to have a benign side-effects profile, and merits further study. Trial Registration: ClinicalTrials.gov identifier: NCT00761761 J Clin Psychiatry 2013;74(11):1076–1083

© Copyright 2013 Physicians Postgraduate Press, Inc. Submitted: February 7, 2013; accepted May 3, 2013 (doi:10.4088/JCP.13m08413). Corresponding author: K. N. Roy Chengappa, MD, Comprehensive Recovery Services, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O’H

3: Stress

JANA Vol. 11, No. 1, 2008

A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo-Controlled Study.

Biswajit Auddy, PhD1; Jayaram Hazra, PhD2; Achintya Mitra, MD2; Bruce Abedon, PhD3; Shibnath Ghosal, PhD1

1. Research and Development Center, Natreon Inc., Salt Lake City, Kolkata, India
2. Central Research Institute (Ayurveda), Ministry of Health and Family Welfare, Govt. of India, Bidhan Nagar, Kolkata, India
3. Director of Scientific Affairs, NutraGenesis LLC, Brattleboro, Vermont

Abstract

Withania somnifera (WS) has historically been used in Asia for treating stress-related health conditions. In this study, we investigated the effects of standardized WS root and leaf extract (WSE) in chronically stressed humans in a modern clinical trial. Participants were randomly assigned to WSE (125 mg QD, 125 mg BID, or 250 mg BID) or placebo groups. Stress levels were assessed at Days 0, 30, and 60 using a modified Hamilton anxiety (mHAM-A) scale. Biochemical and clinical variables were measured at Days 0 and 60. Of 130 subjects enrolled, 98 completed the study. Between Days 0 and 60, the WSE 125 mg QD group decreased significantly more than placebo for mean mHAM-A score, serum cortisol, serum C-reactive protein, pulse rate and blood pressure, and increased significantly for mean serum DHEAS and hemoglobin. Other WSE treatment groups had greater dose-dependent responses in these parameters and had significantly greater responses compared to placebo in mean fasting blood glucose, serum lipid profiles and cardiac risk ratios. Participants and dropouts reported no adverse effects. Therefore, this study provides evidence that the consumption of WSE significantly reduces experiential and biochemical indicators of stress without adverse effects.

Key Words: Withania somnifera, antistress, withanolides, sitoindosides, cortisol, C-reactive protein.

4: Stress

Current Topics in Nutraceutical Research Vol. 11, No. 4, pp. 151-158, 2013

Effect Of Withania Somnifera Extract On Mental Stress Induced Changes In Hemodynamic Properties And Arterial Wave Reflections In Healthy Subjects

Usharani Pingali, Raveendranadh Pilli and Nishat Fatima

Department of Clinical Pharmacology & Therapeutics, Nizam’s Institute of Medical Science, Panjagutta, Hyberabad-500082, India

Abstract

Mental stress is known to contribute to the risk for hypertension and coronary atherosclerosis. Withania somnifera is well known for its anti-stress and antioxidant activity. The present study was done to assess the effect of Withania somnifera extract on acute mental stress induced changes in hemodynamics and arterial wave reflection properties in human participants. In this double-blind, placebo-controlled, randomized, crossover study, 20 healthy participants received 500 mg twice daily of an encapsulated dried aqueous extract of roots and leaves of Withania somnifera or matching placebo for 14 days with a wash out period of 14 days. Blood pressure and central arterial wave reflections were measured noninvasively using Sphygmocor before and after a standardized mental stress test. The results demonstrated an acute effect of mental stress on blood pressure and arterial wave reflections. Withania somnifera extract produced a statistically significant decrease in aortic pressure, augmentation index, radial and aortic SBP, radial and aortic DBP and significant increase in the subendocardial viability ratio (SEVR) compared to baseline and placebo. A significant decrease in hs-CRP, MDA, serum cortisol levels is seen with Withania somnifera extract treatment compared to baseline and placebo. These results suggest that beneficial properties of Withania somnifera extract can mitigate the effects of stress and deserves further investigation in patients with associated diseases.

5: Endothelial Function

International Journal of Ayurveda and Pharma Research, 2014; 2(3): 22-32

EVALUATION OF A HIGHLY STANDARDIZED WITHANIA SOMNIFERA EXTRACT ON ENDOTHELIAL DYSFUNCTION AND BIOMARKERS OF OXIDATIVE STRESS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY

ABSTRACT

Background: Type 2 Diabetes mellitus is a multisystem disorder with oxidative stress and endothelial dysfunction. Withania somnifera Dunal (Ashwagandha) is shown to have potent antioxidant, hypoglycemic and hypolipidemic effects in several studies. The present study was planned to compare the effect of Withania somnifera on endothelial dysfunction and biomarkers in patients with diabetes mellitus. Materials and Methods: After taking IEC approval and written informed consent, 66 eligible patients, who are on metformin therapy, were randomized to receive either one capsule of highly standardized aqueous extract of Withania somnifera 250mg twice daily, one capsule of Withania somnifera 500mg twice daily or Placebo for a duration of 12 weeks. Primary efficacy parameter was a change in endothelial function (measured as change in reflection index of more than 6 %) performed by salbutamol challenge test at baseline and after 12 weeks of treatment. Secondary end points were change in biomarkers of oxidative stress (malondialdehyde, nitric oxide and glutathione), high sensitivity C-reactive protein and change in lipid profile. Safety lab parameters were measured, at baseline and after 12 weeks of treatment. Results: A total of 60 patients completed the study. Twelve weeks of treatment with Withania somnifera 250mg and 500mg produced significant reduction in reflection index (-2.52±1.32% to - 7.49±3.49%) and (-2.24±1.00% to -9.03± 2.42%) respectively, suggesting improvement in endothelial function versus placebo (-2.11±1.62% to -0.81± 2.86%). Similarly a significant improvement in biomarkers of oxidative stress, systemic inflammation, lipid parameters and HbA1c levels, compared to baseline and placebo, was observed with Withania somnifera. All treatments are well tolerated. Conclusion: Withania somnifera showed significant improvement in endothelial function, reduction in biomarkers of oxidative stress and systemic inflammation and can be used as a therapeutic adjunctive in patients with type 2 Diabetes mellitus.

Key Words: Withania somnifera, Ashwagandha, Oxidative stress, Endothelial dysfunction.

6: Ashwagandha a Rejuvenator

Singh et al., Afr J Tradit Complement Altern Med. (2011) 8(S):208-213

AN OVERVIEW ON ASHWAGANDHA: A RASAYANA (REJUVENATOR) OF AYURVEDA

Abstract

Withania somnifera (Ashawagandha) is very revered herb of the Indian Ayurvedic system of medicine as a Rasayana (tonic). It is used for various kinds of disease processes and specially as a nervine tonic. Considering these facts many scientific studies were carried out and its adaptogenic / anti-stress activities were studied in detail. In experimental models it increases the stamina of rats during swimming endurance test and prevented adrenal gland changes of ascorbic acid and cortisol content produce by swimming stress. Pretreatment with Withania somnifera (WS) showed significance protection against stress induced gastric ulcers. WS have anti-tumor effect on Chinese Hamster Ovary (CHO) cell carcinoma. It was also found effective against urethane induced lung-adenoma in mice. In some cases of uterine fibroids, dermatosarcoma, long term treatment with WS controlled the condition. It has a Cognition Promoting Effect and was useful in children with memory deficit and in old age people loss of memory. It was also found useful in neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzeimer’s diseases. It has GABA mimetic effect and was shown to promote formation of dendrites. It has anxiolytic effect and improves energy levels and mitochondrial health. It is an anti-inflammatory and anti- arthritic agent and was found useful in clinical cases of Rheumatoid and Osteoarthritis. Large scale studies are needed to prove its clinical efficacy in stress related disorders, neuronal disorders and cancers.

Key Words: Withania somnifera, rejuvenator, adaptogen / anti-stress, anti-tumor, neuroregenerative, anti-arthritic.

7: Ashwagandha Reduces Lead Toxicity

BioMed Research International, Volume 2014, Article ID 182029, 15 pages http://dx.doi.org/10.1155/2014/182029

Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

Abstract

Withania somnifera (Ashwagandha), also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 ?M to 400 ?M concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 ?M) resulted in normalization of glial fibrillary acidic protein (GFAP) expression as well as heat shock protein (HSP70), mortalin, and neural cell adhesion molecule (NCAM) expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx) levels, catalase, and superoxide dismutase (SOD) but not reduced glutathione (GSH) contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

8: Ashwagandha: Antioxidant Properties

Alam et al. BMC Complementary and Alternative Medicine 2012, 12:175 http://www.biomedcentral.com/1472-6882/12/175

Abstract

Background: Withania somnifera, also known as ashwagandha, is an important herb in ayurvedic and indigenous medical systems. The present study was designed to evaluate the antioxidant and antibacterial activities of an 80% aqueous methanolic extract of W. somnifera roots (WSREt), fruits (WSFEt) and leaves (WSLEt).

Methods: Several assays were performed to determine the antioxidant properties of this herb including

1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity, ferric reducing antioxidant power (FRAP), ferrous chelation and inhibition of β-carotene bleaching.

Results: The values for DPPH, FRAP, ferrous chelation and inhibition of β carotene bleaching for the three types of extracts ranged from 101.73-801.93 μg/ml, 2.26-3.29 mM Fe/kg, 0.22-0.65 mg/ml and 69.87-79.67%, respectively, indicating that W. somnifera, particularly the leaves, possesses significant antioxidant properties. The mean ascorbic acid content was 20.60-62.60 mg/100 g, and the mean anthocyanin content was 2.86-12.50 mg/100 g. Antibacterial activities were measured using the agar well diffusion method and five pathogenic Gram-negative bacteria: Escherichia coli, Salmonella typhi, Citrobacter freundii, Pseudomonas aeruginosa and Klebsiella pneumoniae. The leaf extracts displayed the highest activity against S. typhi (32.00 ± 0.75 mm zone of inhibition), whereas the lowest activity was against K. pneumoniae (19.00 ± 1.48 mm zone of inhibition). The lowest minimum inhibitory concentration value was 6.25 mg/ml, which was against S. typhi, followed by 12.5 mg/ml against E. coli.

Conclusion: In addition to its antioxidant properties, W. somnifera exhibited significant antibacterial activities against Gram-negative bacteria, particularly S. typhi.

Key Words: Withania somnifera, Antioxidant, Antibacterial, Free radicals, FRAP

9: Pain

Usharani et al / Research Journal of Life Sciences (May- 2013), Vol. 01, Issue 02, pp.1-6

Evaluation of the analgesic activity of standardized aqueous extract of Withania somnifera in healthy human volunteers using Hot Air Pain Model.

Abstract

Pain is the most prevalent health care problem. Most analgesics available today have good analgesic activity but are associated with lot of side effects. So analgesics with minimal side effects are required which can be evaluated by hot air pain model in healthy volunteers. Withania somnifera with various properties due to its active constituents-withanolides is widely used in Ayurvedic medicine. This study was done to evaluate the analgesic effect and tolerability of single oral dose (1000mg) of standardized aqueous extract of Withania somnifera using Hot Air Pain model in healthy human volunteers as per ICH GCP Guidelines after taking written informed consent to protocol approved by IEC. Subjects were randomised to receive either single oral dose of 1000mg standardized aqueous extract of Withania somnifera or identical placebo in a double blind manner. Mean Pain Threshold Time at baseline and 3hrs after drug administration were noted. Washout period of 10-14 days was given for cross-over between the two treatments. Safety assessments were conducted before and at end of study Total twelve subjects were enrolled. Mean Pain Threshold Time with Withania somnifera increased from 43.99±6.79 to 49.89±7.07 sec (p<0.05). No significant change was observed with placebo. Both drugs were well tolerated.

Key Words: Withania somnifera, Hot Air Analgesiometer, Pain Threshold Time.

10: Alzheimer’s Disease

www.pnas.org/cgi/doi/10.1073/pnas.1112209109

Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver

Abstract

A 30-day 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 β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer’s disease trans- genic 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 Aβ and a decrease in brain Aβ mono- mer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ- degrading protease neprilysin (NEP) occurred 14–21 d after a substantial decrease in brain Aβ 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 Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and de- creased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. 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 Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer’s disease models.

Key Words: herbal extract | dementia | neurodegenerative disease

11: Review of Studies

Pharmacognosy Reviews Vol 1, Issue 1, Jan- May, 2007

Withania somnifera (Ashwagandha): A Review

Abstract

Withania somnifera, a commonly used herb in Ayurvedic medicine. Although the review articles on this plant are already published, this review article is presented to compile all the updated information on its phytochemical and pharmacological activities, which were performed by widely different methods. Studies indicate ashwagandha possesses antioxidant, anxiolytic, adaptogen, memory enhancing, antiparkinsonian, antivenom, anti-inflammatory, antitumor properties. Various other effects like immunomodulation, hypolipidemic, antibacterial, cardiovascular protection, sexual behaviour, tolerance and dependence have also been studied. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.

Key Words: Withania somnifera, Withanolides, Phytochemistry, Pharmacological activities.

12: Improved Memory

Search for natural products related to regeneration of the neuronal network. Neurosignals. 2005;14(1-2):34-45;
Tohda C, Kuboyama T, Komatsu K.

Abstract:

The reconstruction of neuronal networks in the damaged brain is necessary for the therapeutic treatment of neurodegenerative diseases. We have screened the neurite outgrowth activity of herbal drugs, and identified several active constituents. In each compound, neurite outgrowth activity was investigated under amyloid-beta-induced neuritic atrophy. Most of the compounds with neurite regenerative activity also demonstrated memory improvement activity in Alzheimer's disease-model mice. Protopanaxadiol-type saponins in Ginseng drugs and their metabolite, M1 (20-O-beta-D-glucopyranosyl-(20S)-protopanaxadiol), showed potent regeneration activity for axons and synapses, and amelioration of memory impairment. Withanolide derivatives (withanolide A, withanoside IV, and withanoside VI) isolated from the Indian herbal drug Ashwagandha, also showed neurite extension in normal and damaged cortical neurons. Trigonelline, a constituent of coffee beans, demonstrated the regeneration of dendrites and axons, in addition to memory improvement....

13: Improved Memory

Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005 Apr;144(7):961-71.
Kuboyama T, Tohda C, Komatsu K.

Abstract:
"We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. ... Subsequent treatment with WL-A ... induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A ... recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks."

14: 4Improved Memory4

Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha. Neuroreport. 2002 Oct 7;13(14):1715-20.
Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K.

Abstract:
"We previously reported that the methanol extract of Ashwagandha (roots of Dunal) induced dendrite extension in a human neuroblastoma cell line. In this study, we found that six of the 18 compounds isolated from the methanol extract enhanced neurite outgrowth in human neuroblastoma SH-SY5Y cells. ... In withanolide A-treated cells, the length of NF-H-positive processes was significantly increased compared with vehicle-treated cells, whereas, the length of MAP2-positive processes was increased by withanosides IV and VI. These results suggest that axons are predominantly extended by withanolide A, and dendrites by withanosides IV and VI."

15: Improved Memory

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo). 2002 Jun;50(6):760-5.
Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K.

Abstract:
Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.

16: Brain Health

Propensity of Withania somnifera to Attenuate Behavioural, Biochemical, and Histological Alterations in Experimental Model of Stroke. Cell Mol Neurobiol. 2015 Dec 30

Sood A, Kumar A, Dhawan DK, Sandhir R.

Abstract:

The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

Keywords:

Antioxidant; Behaviour; Cerebral ischemia; Oxidative stress; Withania somnifera

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