Withania Somnifera Extract Research Articles

Effects of Withania somnifera Nicotine Induced Conditioned Place Preference in Mice

Background: Herbal medicines can be novel treatment strategies for management of nicotine addiction. Withania somnifera (Ashwagandha) is an Indian medicinal plant of great medicinal value; used in many clinically proven conditions. Objective: In present study we aimed at investigating the effect of withania somnifera extract (WSE) on preventing nicotine mediated effects attributed for the development of addiction. Material and Methods: Mice were treated with nicotine and/or WSE and subjected to nicotine induced conditioned place preference (CPP) in male albino mice was checked. Results: Application of two-way ANOVA showed that with preconditioning and post-conditioning values as a within-subjects (column) factor and treatment as an independent between subject (row) factor. Two-way ANOVA revealed significant effect of treatment [F(3,40)=4.119, p<0.05], time [F(1,40)=23.76, p<0.001] and interactiontreatment x time [F(3,40)=5.244, p<0.01] on Intra-peritoneal (ip) administration of nicotine (1 mg/kg). WSE did not produce any changes in the preference to drug-paired compartment. Factors like treatment [F(3,40) = 0.656, p>0.05], time [F(1,40) = 7.383, p<0.01] and interactiontreatment x time [F(3,40) = 0.5748, p>0.05] showed insignificant effects. Withania somnifera (50,100,200 mg/kg ip) coadministered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Conclusion: Above data indicate that withania somnifera attenuate nicotine induced CPP. Hence it has potential as an anti-addictive therapy.

Amelioration of Titanium Dioxide nanoparticles induced injury on the cerebellum of the adult mice by a hydromethanolic root extract of Withania Somnifera

Introduction: Titanium Dioxide (TiO2) nanoparticles have potential risks to human health. They were able to enter brain to be detected in the cerebral cortex, cerebellum and hippocampus. Withania somnifera (WS) improve rotenone induced damage in cerebellum.Aim of the work: To study the effects of oral administration of TiO2 nanoparticles on the cerebellum and the protective role of hydromethanolic root extract of WS (Egyptian Ashwaghandha).Material and Methods: Seventy five adult male albino mice were divided into five groups (N=15): group 1 (control), group 2 (gum acacia group), and group 3 (WS root extract group) recieved orally hydromethanolic WS root extract (500 mg/kg) once daily, group 4 (TiO2 nanoparticles group) recieved orally TiO2 nanoparticles (150 mg/ Kg), dissolved in gum acacia solution once daily, group 5 (TiO2 nanoparticles + WS root extract group). After sixty days, Sections from the cerebellum were prepared and stained with HandE, Cresyl violet stain as well as Immunohistological stains for nNOS, iNOS, eNOS and GFAP. Morphometrical and statistical analyses were performed.Results: In TiO2 nanoparticles group, cerebellum showed disrupted purkinje cells with marked degenerative changes, decreased Nissl granules in Purkinje cells, vacuolations in all layers of the cerebellar cortex and dilated congested capillaries in white matter. The number of the Purkinje cell were decreased while GFAP positive astrocytes were increased. Decreased nNOS immunostaining in cortical layers, while the iNOS immunostaining increased and increased eNOS immunostaining in capillary endothelial cells were detected. Administration of the hydromethanolic WS root extract improved the altered cerebellar morphology with significant statistical improvement in purkinje cell and astrocyte count.Conclusion: TiO2 nanoparticles oral administration induced toxic effects and WS contains active ingredients that counteract these effects.

Effect of Extracts of Capparis spinosa, Withania somnifera and Peganum harmala on Aspergillus flavus Growth and Expression of Major Genes in Aflatoxin Biosynthetic Pathway

Background: Aflatoxins, a polyketide group derived from furanocoumarins, are highly toxic carcinogens produced by Aspergillus flavus and other closely related species. Objectives: In this research, the effects of Capparis spinosa, Withania somnifera, and Peganum harmala extracts on A. flavus growth and the expression of some major genes in aflatoxin biosynthetic pathway were investigated. Methods: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were measured and the expression of aflQ, aflO, aflS, and aflR genes was evaluated by using quantitative real-time polymerase chain reaction (qRT-PCR) technique. Results: Capparis spinosa extract had the lowest MIC value (200 mg/mL) and the extracts of W. somnifera and P. harmala had the highest MIC value (400 mg/mL). The extracts of W. somnifera and P. harmala had no fungicidal activity, and the C. spinosa extract had the lowest MFC value (400 mg/mL) and had the highest fungicidal effect on A. flavus. The expression of aflQ, aflO, aflS, and aflR genes was significantly decreased by the C. spinosa extract. Conclusions: In general, the C. spinosa extract could have fungicidal and inhibitory effects on A. flavus and reduce expression of major genes in the aflatoxin biosynthetic pathway.

Abstract 5828: Withaferin A and tumor treating fields synergistically inhibit glioma proliferation

Abstract Glioblastoma multiforme (GBM) is the most lethal primary brain cancer (median survival: 15-17 months, 5-year survival: 5-10%). Current interventions consist of equally aggressive surgical resection, radiotherapy, and chemotherapy. However, this cancer is heterogeneous and not easily accessible so standardized, non-specific therapies are often ineffective. Novel, unorthodox approaches against GBM need consideration. Withaferin A is a steroidal lactone that originates from the roots and leaves of the winter cherry plant (Withania somnifera). Within Ayurvedic medicine, Withania somnifera extracts are applied to many disorders including several cancers. Extracts such as AshwaMAX can contain up to 4.3% (w/w) Withaferin A, a biologically active compound from Withania somnifera. Tumor Treating Fields (TTFields) are thought to disrupt mitotic spindle formation and stymie proliferation of actively dividing cancer cells. We report on the anti-cancer properties of both Withaferin A and TTFields. We also examined the hypothesis that combining TTFields with Withaferin A would synergistically inhibit GBM growth. We used GBM cells (U87-MG, GBM2, and GBM39) and breast adenocarcinoma cells (MDA-MB-231) isolated from human primary tumors. Each GBM cell line was modified to express firefly luciferase. Proliferative potential was assessed by bioluminescent imaging (BLI), cell counting via hemocytometer, or through the CellTiter-Blue® viability assay. Intracranial orthotopic U87-MG GBM xenografts were grown in the right frontal lobe of female nude mice (n=5/experiment). TTFields were imposed on cell cultures with the inovitroTM system from Novocure Ltd. Neurosphere cultures (U87-MG, GBM2, and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 µM (Withaferin A equivalent), respectively, and by Withaferin A with IC50 of 0.31, 0.28, and 0.25 µM, respectively. Oral gavage, every other day, of AshwaMAX (40mg/kg per dose) significantly reduced BLI signal (n=5 mice/group, p&amp;lt;0.02, four-parameter non-linear regression analysis) in preclinical models. Comsol modeling showed that the inovitroTM device imposed optimal TTFields in the center of the cell culture dishes. TTFields at 4 V/cm significantly inhibited (n=4 measurements per time point, p&amp;lt;0.001, 2-way ANOVA) growth of MDA-MB-231 cancer lines and all three human GBM lines. The effects were due to the TTFields alone and not to the slight temperature rises caused by the TTFields. Combination of Withaferin A (10-100 nM) with TTFields (4 V/cm) significantly inhibited GBM growth, to a degree beyond that of Withaferin A or TTFields alone. Poisson-based analysis of significance for regression indicated that the interaction of the combined treatments on GBM cells was synergistic (p&amp;lt;0.01, n=3 experiments). The findings suggest a novel approach to treat GBM in a manner that is likely better than either treatment (Withaferin A or TTFields) alone and that is synergistic. Citation Format: Edwin Chang, Chirag Patel, Christoph Pohling, Nooshin Beygui, Dong Ho Ha, Sanjiiv S. Gambhir. Withaferin A and tumor treating fields synergistically inhibit glioma proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5828.

Study the Effect of Water Extracts of Some Plants Against Fungus Macrophomina Phaseolina That Causes Charcoal Rot on Common Beans

The objective of this study was to study the effect of water extracts of plants from the local environment on the growth of fungus Macrophomina Phaseolina. Laboratory results showed a positive effect of water extracts in inhibiting the growth of pathogenic fungus where the percentage of inhibition of extracts (Alknah) Kanahia laniflora, Oleander Nerium, Eucalyptus camaldulensis, (Alsniffh) Argemone mexicana, (Alabb) Withania somnifera, (Alothurb) Rumex nervosus, respectively, 64.07%, 42.96%, 42.58%, 41.86%, 33.48%, and 22.96%. As for the greenhouse experiments results showed an increase in germination percentage and a reduction in the incidence of charcoal rot after 15 days from sowing to treatments of Eucalyptus, Withania somnifera, Argemone mexicana, Kanahia laniflora, and Oleander Nerium, Where the percentage of germination of these treatments were 100%, 96.66%, 96.66%, 96.66%, 93.33%, respectively, and the percentage reduction in the incidence of the same treatments were 0.00%, 3.33%, 3.33%, 3.33%, 6.66%, respectively, compared to the extract of Rumex nervosus and control (untreated seeds) where the infection rates were 43.333% and 25%,respectively. After 45 days from sowing, each plant extract showed positive effects in reducing the incidence of cause charcoal root on the beans. The rate of the reduction in the incidence were 7.67%, 11.67%, 33.33%, 40.00%, 43.33% and 46.67% for the extracts of Kanahia laniflora, Eucalyptus, Oleander Nerium, Argemone mexicana, Rumex nervosus and Withania somnifera, respectively, Compared to the control (non-treated seeds) 76.67%. The results also, showed that the plant extracts had no effect on fresh weight and dry weight of shoot. On the other hand, the results showed that the extract of Rumex nervosus and eucalyptus had positive results in fresh weight gain of the root system by 1.58, 1.36 g., respectively, comparing with 0.71 g. for the control. Rumex nervosus extract showed positive results as an increase in the dry weight of the roots, followed eucalyptus camaldulensis and Nerium oleander 0.21, 0.15, 0.14 g., respectively, comparing with the control 0.11 g. Accordingly, the plant extracts of some plants from the Yemeni environment have the ability to inhibit the growth of pathogens and can be used to control plant diseases to reduce the use of chemical fungicides and reduce the extensive damage to humans and the environment.

Withania somnifera attenuates nicotine induced locomotor sensitization and withdrawal symptoms in mice

Objective: To investigate the effect of withania somnifera extract (WSE) on nicotine mediated reinforcement effect and withdrawal symptoms which attributed for the addiction liabilities of nicotine. Methods: In Swiss albino mice nicotine mediated locomotor sensitization and anxiogenic effects of chronic and acute nicotine treatment respectively was tested per se or in combination with WSE. In addition, nicotine withdrawal induced anxiety-like behavior was also studied. Locomotor sensitization was tested by employing open field test (OFT), while symptoms of anxiety were evaluated by subjecting mice to elevated plus maze (EPM). Results: Daily treatment with nicotine (subcutaneous) for 7 days showed gradual increase in the locomotor activity in OFT as compared to saline group indicating the development of locomotor sensitization. Following 3 days of drug free period, nicotine challenge on day 11 also showed rise in locomotor activity depicting expression of sensitization. WSE pretreatment inhibited the nicotine induced development and expression of locomotor sensitization. WSE+nicotine treated group showed decreased ambulations as compared to per se nicotine group on day 1-7 and day 8 (P&lt;0.05). In EPM, acute nicotine treated mice spend more time in open arms as compared to saline indicating the anxiolytic behavior. WSE pretreatment reversed this anxiolytic effect. Nicotine withdrawal mice showed significant increase in the number of entries in arm and total time spend in closed arm indicating anxiety-like behavior. WSE treatment in nicotine withdrawal mice inhibited the nicotine withdrawal induced increased number of entries and time spend in closed arms. Conclusion: These results indicated that WSE may serve an effective herbal medicine in arresting nicotine mediated reinforcement and withdrawal signs.

A natural product composition targeting oxidative stress induced mitochondrial dysfunction in Alzheimer's Disease

Mitochondria regulates cellular metabolism and apoptosis. Oxidative stress induced mitochondrial dysfunction, appears to play a role in the pathogenesis of Alzheimer's disease. Natural antioxidants have been known to play an important role in alleviating the deleterious effects induced by free radicals by blocking the initiation and propagation of oxidizing chain reactions. Hence, the study hypothesizes the effect of natural product composition (combinatorial extract of Eclipta alba, Morinda pubescens and Withania somnifera) on restoring the mitochondrial functional capacity and mitochondrial enzyme levels. The individual and combinatorial methanolic extracts of dried whole plants of Eclipta alba (MEEA), dried fruits of Morinda pubescens (MEMP) and dried roots of Withania somnifera (MEWS) and MECE were prepared. The extracts were screened for in vitro antioxidant activity by DPPH assay. A rodent behavioural model to assess the effect of the extracts on short term memory was performed subsequent to scopolamine hydrobromide induced amnesia and oxidative stress. The brain homogenates from these rodents were subjected to screening in vivo antioxidaint activity using a battery of assays. The effect of extracts on restoring mitochondrial functional capacity (using MTT assay) and the levels of key mitochondrial enzymes succinate dehydrogenase and isocitrate dehydrogenase; was performed using synaptosomal fractions prepared from rodent brain samples.MEEA, MEMP, MEWS and MECE compared with ascorbic acid exhibited 50% scavenging effect at 69.34 μg/ml, 72.19 μg/ml, 65.84 μg/ml, 45.09μg/ml and 57.64 μg/ml, respectively by DPPH assay. Pretreatment with MEEA, MEMP and MEWS at the doses 50,100 and 200 mg/kg and MECE at 50 and 100mg/kg for 8 days followed by scopolamine hydrobromide treatment significantly (p&lt;0.001) improved the antioxidant defense system, the mitochondrial functional capacity and mitochondrial enzyme levels.The natural product composition strengthened the endogenous antioxidant defense system, restored the mitochondrial functional capacity and enzyme levels. Hence, it has a potential neuroprotective role in Alzheimer's disease which needs to be investigated further in a clinical setting.Support or Funding InformationNMIMS UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Efficacy of Supplementing Ashwgandha Extract (Withania somnifera) on Immunity and Serum Biochemitry in Broilers During Summer

The objective of present study was to determine the effects of different levels of Ashwagandha (Withania somnifera) extract (WSE) on immunity and serum biochemical parameters of broiler chicken reared during hot summer. The average minimum and maximum room temperatures recorded from 0-42 day were 36.8oC±0.25 – 39.7oC±0.25, respectively, with relative humidity ranging from 47 – 74%. Day old broiler chicks (n=160) were randomly allotted to 4 dietary groups with eight replicates of five birds each. The four groups were Positive control (PC) with vit-E (70mg/kg) +Se (0.15mg/kg), Negative control (NC), WSE50 and WSE100 groups supplemented with WSE 50mg/kg and 100mg/kg, respectively. Serum cholesterol levels were significantly (P0.05) by supplementation of WSE. Humoral immune response in terms of NDV (Newcastle disease virus) titer and cell mediated immunity in terms of cutaneous basophilic hypersensitivity (CBH) were not significantly influenced by supplementation of WSE in broiler diets.

Triethylene glycol-like effects of Ashwagandha (Withania somnifera (L.) Dunal) root extract devoid of withanolides in stressed mice.

Background:The objective of the study is to compare stress resistance-promoting effect of triethylene glycol (TEG) and root extract of Ashwagandha (Withania somnifera) i.e. withanolide-free root extract of Withania somnifera (WFWS).Materials and Methods:Mice groups treated orally with 10 mg/kg TEG or WFWS (3.3, 10, 33.3, or 100 mg/kg) for 12 consecutive days were subjected to foot shock stress-triggered hyperthermia test on the 1st, 5th, 7th and 10th day and to marble-burying test on the following 2 days. Effects of treatment on stress-triggered alteration in body weight, core temperature, blood glucose, insulin and cortisol level were quantified and statistically analyzed.Results:WFWS doses up to 10 mg/kg/day were as effective as TEG in affording protection against stress-triggered alteration in body weight, core temperature and marble-burying behavior. Protection against stress-triggered alteration in blood glucose and insulin level, as well as antidepressants or anxiolytic-like activities in the behavioral test, were observed in the higher two WFWS doses (33.3 and 100 mg/kg) treated groups only.Conclusion:Ashwagandha metabolites other than withanolides contribute to its stress resistance increasing effects. The observations suggest that modulation of physiological functions of gut microbiota may be involved in the mode of action of Withania somnifera root extracts.

INHIBITORY POTENCY OF WITHANIA SOMNIFERA EXTRACTS AGAINST DPP-4: AN IN VITRO EVALUATION

Background: Pharmacologic treatments for type 2 diabetes are based upon increasing insulin availability and improving sensitivity to insulin. Nowadays, glucagon like peptide-1 (GLP-1) based therapies aims at glucose control through DPP-4 inhibitors. DPP-4 is a transmembrane glycoprotein belongs to prolyl oligopeptidase family, with the specificity of removing X-Pro or X-Ala dipeptides from the N-terminus of polypeptides. GLP-1 effect by stimulating glucose-dependent insulin release from the pancreatic islets, inhibit inappropriate post-meal glucagon release and slow gastric emptying promoting leaky gut. The current study investigated DPP-4 inhibitory activity of catechin, isolated from Withania somnifera (WS), for ethnopharmacological treatment of type 2 diabetes and aimed to increase availability of GLP-1and sensitivity to insulin.&#x0D; Materials and Methods: Young and matured fresh roots, leaves, and fruits of WS plant extract were considered and were systematically evaluated for DPP-4 inhibitory activity using in vitro method, enzyme kinetics, phytochemical analysis, RP-HPLC, LCMS and 1H and 13C NMR method and structure-activity relationship (SAR) studies.&#x0D; Results: In this study, methanol (100% and 80%) extracts of WS matured root exhibited maximum DPP-4 inhibitory activity when compared to other extracts. The maximum DPP-4 inhibitory activity was found in 100% methanol extract of matured root. Phytobioactive was purified by RP-HPLC. The compound purified was found to be flavonoid and was characterized (LCMS, 1H and 13C NMR studies), identified as catechin. Auxiliary, molecular docking was performed using Ligand Fit method using PatchDock package. The study revealed the binding affinity of catechin with DPP-4 to be -6.601 kcal/mol with 13 hydrogen interactions with the receptor and was very similar to the standard potent blockers withaferin A and others (cuscohygrine, scopoletin, sitoindoside IV, tropine), further confirming its hyperglycemic potency.&#x0D; Conclusion: The study reveals that, 100% methanol extract of WS matured roots contains the compound- catechin, which exhibits DPP-4 inhibitory activity resulting in increased level of bioactive GLP-1 and GIP. In this background, we concluded that the WS will be a better source for further development as new antidiabetic drugs.

Herbal pre-conditioning induces proliferation and delays senescence in Wharton’s Jelly Mesenchymal Stem Cells

BackgroundMesenchymal Stem Cells (MSCs) are multipotent stem cells which are being explored for various clinical applications. Isolation and in-vitro expansion of MSCs remain important in achieving desired cell number for the therapy. However, in-vitro proliferation of MSCs is often associated with senescence and early onset of apoptosis which limits its therapeutic ability and long term clinical use. Tinospora cordifolia and Withania somnifera are used widely in Ayurveda: the traditional Indian system of medicine and are reported to have rejuvenating and anti-aging potential. In the present study, we investigated the effect of Tinospora cordifolia and Withania somnifera on proliferation and senescence of wharton’s jelly MSCs (WJMSCs) in-vitro. MethodsWJMSCs were treated in culture medium with Tinospora cordifolia leaf and Withania somnifera root extracts to examine their effect on proliferation and senescence properties of WJMSCs. Proliferation of WJMSCs was assayed by cell count, MTT, BrdU incorporation assay, cell cycle analysis and Ki67 mRNA expression. Senescence was demonstrated using β-galactosidase senescence assay and associated mRNA markers. ResultsCulture medium supplemented with Tinospora cordifolia leaf and Withania somnifera root extracts exhibited significant increase in proliferation of WJMSCs as evidenced by cell count and MTT assay. Cell cycle analysis using propidium iodide showed increase in G2/M phase and decrease in apoptotic cells. BrdU incorporation and upregulation of proliferation marker ki67 by RT PCR showed increased DNA synthesis/proliferation in Tinospora cordifolia and Withania somnifera extract treated MSCs. Delayed senescence was confirmed by β-galactosidase senescence assay and down regulation of senescence marker p21. ConclusionOur results demonstrate for the first time that Tinospora cordifolia and Withania somnifera extracts support proliferation and inhibit senescence in WJMSCs making them suitable candidates as supplements for in-vitro expansion without affecting the cell viability indicating its non-toxic nature.

Withania somnifera Root Extract Enhances Chemotherapy through 'Priming'.

Withania somnifera extracts are known for their anti-cancerous, anti-inflammatory and antioxidative properties. One of their mechanisms of actions is to modulate mitochondrial function through increasing oxidative stress. Recently ‘priming’ has been suggested as a potential mechanism for enhancing cancer cell death. In this study we demonstrate that ‘priming’, in HT-29 colon cells, with W. somnifera root extract increased the potency of the chemotherapeutic agent cisplatin. We have also showed the W. somnifera root extract enhanced mitochondrial dysfunction and that the underlying mechanism of ‘priming’ was selectively through increased ROS. Moreover, we showed that this effect was not seen in non-cancerous cells.

Acute and Sub-Chronic Toxicological Potential of Withania Somnifera Extract on Rats

Withania somnifera (WS) has a wide range of therapeutic applications for several disorders. Toxicity studies on WS are very limited. The purpose of the present work is to study the acute and sub-chronic toxicity of WS extracts in rats and to determine the LD50 value, which helps in determining the safe dose range for the plant extract to be used with no harmful or lethal effects on the animal. Rats in the acute study were IP injected with the alcoholic extract of WS (the arial parts) at doses of (0), 150, 300, 600 and 1200 mg/kg bwt. In sub-chronic toxicity study, WS extract was administered IP at a dose of 10%, 20% and 40% of the obtained LD50 (52 mg/kg bwt, 104 mg/kg bwt and 208 mg/kg bwt respectively) for 60 days. Acute toxicity revealed an IP LD50 of 522 mg/kg wt. Significant changes in body weight, hematological, biochemical and histopathological were recorded in 20% and 40% LD50 groups with 15 – 40 % mortalities respectively, by the end of the experiments. Based on this study, WS showed toxicity at doses higher than 10% LD50 when given IP and it was recommended to use ≤ 10% LD50 (IP) doses of WS extracts, than the tested here to start within setup protection or treatment studies.

Withanolides against TLR4-Activated Innate Inflammatory Signalling Pathways: A Comparative Computational and Experimental Study.

Innate inflammations are dominant causes of poor health and high mortality. The pathogen-associated molecular pattern and lipopolysaccharide (LPS) are sensed by immune cells through activation of toll-like receptor 4 leading to mitogen-activated protein kinases (MAPKs) and NF-κB activations. Controlled MAPK and Nf-κB inhibitors have been proposed as potential antiinflammatory drugs. Withania somnifera is an important medicinal herb with known antiinflammatory activity. In this study, the selected Withania somnifera extracts and withanolides were analysed on LPS-induced macrophages comparatively. Molecular docking analysis revealed withaferin A, withanone and withanolide A as effective withanolides against inflammatory target molecules. In experiments, withaferin A and withanone treatment had prominent suppressions on LPS-induced expression of pro-inflammatory cytokines in bone marrow-derived macrophages. Withaferin A regulated all the major four pathways (MAPKs and NF-κB) involved in innate inflammations. Similarly among the Withania extracts analysed, the in vitro propagated leaf and field grown root extracts containing high withaferin A content suppressed the inflammatory molecules through NF-κB and MAPK pathways. Withaferin A was found to be best in suppressing the activated inflammatory pathways among all the analysed withanolides. Therefore, withaferin A and extracts with high withaferin A content can be used as promising drug candidates against innate inflammations. Copyright © 2016 John Wiley & Sons, Ltd.

Analgesic activity of a Withania somnifera extract in stressed mice

Withania somnifera is an important Ayurvedic Rasayana herb, the roots of which are often used in traditionally known systems of medicine as tonic or for rejuvenation purposes. Effects of a single and ten daily oral doses (10, 20 and 40 mg/kg) of an analytically well standardized Withania somnifera root extract against foot shock stress triggered transient hyperthermia and hotplate test for analgesics in male mice were quantified. Body weights and basal rectal temperatures of animals were recorded on all observational days and on the 11th and 12th day of the experiment, all animals were subjected to tail suspension and pentobarbital hypnosis tests respectively. Daily dose dependent efficacy of the tested extract in stress induced hyperthermia test and in hot plate test increased with increasing number of treatment days, and its dose dependent inhibitory effect on immobility time in tail suspension were observed after its 11 daily oral doses. Daily handling and intermittent foot shock stress triggered body weight losses and elevations in basal core temperatures were almost completely prevented even by its lowest daily dose (10 mg/kg/day) tested. Repeated daily low oral doses of the Withania somnifera extract is effective in suppressing diverse stress responses, and its centrally acting analgesics and anxiolytics or antidepressants like efficacies increase with increasing numbers of treatment days. These observations reaffirm that Withania somnifera is an adaptogenic herb, and suggest that its effective therapeutic doses has to be adjusted according to the pre-existing allostatic load of patients.

Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats

BackgroundTo investigate the effect of the combination of hydroalcoholic extract of Withania somnifera (WS) and Tribulus terrestris (TT) on letrozole induced polycystic ovarian syndrome (PCOS) in rat. MethodsTwenty four female Wistar rats of regular estrus cycle were divided into four groups of six animals each. The negative control group received 1mL of 0.5% carboxy methyl cellulose. The animals of the other groups were treated with letrozole (1mg/kg) for 21 days for induction of PCOS. The animals of the positive control group were sacrificed on the 22nd day. In the test and standard groups, the treatment was started from the 22nd day and continued for a further 28 days. The test group was treated with hydroalcoholic extract of the combination of WS and TT (198mg/kg) and the standard group with clomiphene citrate (1mg/kg). Throughout the study, vaginal smears were collected daily from each animal for the determination of different phases of the estrus cycle. After completion of the treatment schedule all the animals of each group were sacrificed; analysis of hormones, total cholesterol, blood glucose, ovarian and uterine weight, and histopathological study of the ovary were carried out. ResultsThe combination of the test drugs showed significant effects in normalizing the estrus cycle after being altered by letrozole. In the positive control group follicle-stimulating hormone level was decreased although luteinizing hormone, estradiole, and testosterone levels were increased (p<0.05), however, after treatment the reverse effect was observed in the level of these hormones. Significant reduction in serum total cholesterol was also observed (p<0.05). The test drugs decreased ovarian weight, and uterine weight was also returned to normalcy. Histopathology of the ovary showed almost normal ovary. ConclusionThe above findings indicate the effectiveness of the combination of hydroalcoholic extract of WS and TT against letrozole induced polycystic ovarian syndrome in rat. This validates the usefulness of combination in PCOS and other related disorders as mentioned by Unani physicians.

The effects of hydroalcoholic extracts of Withania somnifera root, Withania coagulans fruit and 1,25-dihydroxycholecalciferol on immune response and small intestinal morphology of broiler chickens

ABSTRACTThis study was performed to evaluate the effects of hydroalcoholic extracts of Withania somnifera (WS) root, Withania coagulans (WC) fruit, and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on immune response and small intestinal morphology of broiler chickens. A total of 550 male one-day-old Ross 308 broiler chickens were randomly allotted to 55 pens, with 10 birds per pen (replicate), and reared for 42 days. Broiler chickens were fed 11 dietary treatments including a positive control diet with adequate Ca; a negative control diet (Ca concentration reduced by 30%); and the negative control diet supplemented with either WS or WC extracts at three levels (0, 75, and 150 mg/kg diet) or 1,25(OH)2D3 at two different levels (0 and 0.5 μg/kg diet). Antibody response against sheep red blood cells (SRBC) was measured on days 32 and 39. Administration of 150 mg/kg WS and WC significantly increased the production of IgG specific to SRBC on primary and secondary antibody response, respectively. Birds given a negative control diet supplemented with only 150 mg/kg WS displayed the highest villus width compared to those given 75 mg/kg WS or WC with 1,25(OH)2D3. The present study showed that supplementation of WS or WC at 150 mg/kg had beneficial effects on humoral immune response. Also, administration of WS significantly increased villus width.

Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study

BackgroundThe use of Withania somnifera is increasing due to a number of its chemical constituents found useful for health. ObjectiveThe present study was carried out to investigate the potential adverse effects (if any) of a standardized Withania somnifera extract (WSE) in rats following acute and sub chronic administration. Materials and methodsThe toxicity study was performed in Wistar rats by oral administration. An acute toxicity study was done at the dose of 2000 mg/kg. In the sub-acute study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 500, 1000, 2000 mg/kg body weight/day of WSE for 28 days. Among two additional satellite groups, one group did not receive any drug while the second group received 2000 mg/kg/day for 28 days. At the end of study, the animals sacrificed and their body weight, hematology, serum chemistry, and histopathology evaluation was done. ResultsIn acute toxicity studies, oral LD50 of WSE in Wistar rats was greater than 2000 mg/kg body weight. Compared to the control group in sub-acute toxicity study, administration of extract did not show any toxicologically significant treatment related changes in clinical observations, ophthalmic examination, body weight gain, feed consumption, clinical pathology evaluation, and organ weight. Hematological and serum chemistry parameters were within the normal limits. Terminal necropsy did not reveal any treatment related gross or histopathological findings. ConclusionBased on this study, the no-observed-adverse-effect-level of WSE is 2000 mg/kg body weight, the highest level tested.

One-Step Method for Formation of Silver Nanoparticles Using Withania somnifera Extract for Antimicrobial Activities

One-Step Method for Formation of Silver Nanoparticles Using <i>Withania somnifera</i> Extract for Antimicrobial Activities

Evaluation of effect of highly standardized aqueous extract of roots and leaves of Withania somnifera on cold pressor test induced cardiovascular changes in healthy human subjects

Background: Stress is an important cardiovascular risk factor. Cold pressor test (CPT) is a simple, validated, non-invasive test used to measure stress induced changes in cardiovascular parameters. The objective of this study was to evaluate effect of Withania somnifera extract on cold pressor stress test induced changes on cardiovascular parameters and aortic wave reflections in healthy human subjects. Methods: This was a double-blind, placebo controlled, crossover study. Participants were randomized to receive either two capsules of Withania somnifera extract 250 mg or two capsules of placebo twice daily for 14 days. Pharmacodynamic parameters heart rate, aortic pressure, augmentation index (AIx), subendocardial viability ratio (SEVR), radial and aortic blood pressure (BP) were recorded before and after CPT at baseline and at end of treatment. After washout period of 10 days, subjects crossed over to other treatment group and same procedure was repeated. Safety assessments were done at baseline and at end of treatment. Results: A total of 20 volunteers completed the study. Compared with baseline and placebo, Withania somnifera extract produced a significant decrease in mean percent change of arterial stiffness indices (AIx, radial and aortic BP). SEVR with CPT increased, however it was non-significant compared to baseline and placebo. Both treatments were well-tolerated and no serious adverse events were reported. Conclusions: Withania somnifera extract showed a significant decrease in cold pressor stress test induced changes on aortic wave reflections, suggesting its beneficial effects in reducing stress induced cardiovascular changes. However, further clinical studies are warranted to evaluate these effects in patients with cardiovascular and other associated diseases.