Roots of Withania somnifera Inhibit Forestomach and Skin Carcinogenesis in Mice

We evaluated the cancer chemopreventive efficacy of the Withaniasomnifera root, which has been used in the Indian traditionalmedicine system for many centuries for the treatment of variousailments. Since, studies showing its mechanism-based cancerchemopreventive efficacy are limited, this was investigatedin the present study. We studied the effect of dietary administrationof Withania root on hepatic phase I, phase II and antioxidantenzymes by estimation of its level/activity, as well as in attenuatingcarcinogen-induced forestomach and skin tumorigenesis in theSwiss albino mouse model. Our findings showed that roots ofW.somnifera inhibit phase I, and activates phase II and antioxidantenzymes in the liver. Further, in a long-term tumorigenesisstudy, Withania inhibited benzo(a)pyrene-induced forestomachpapillomagenesis, showing up to 60 and 92% inhibition in tumorincidence and multiplicity, respectively. Similarly, Withaniainhibited 7,12-dimethylbenzanthracene-induced skin papillomagenesis,showing up to 45 and 71% inhibition in tumor incidence and multiplicity.In both studies, Withania showed no apparent toxic effects inmice as monitored by the body weight gain profile. Together,these findings suggest that W.somnifera root has chemopreventiveefficacy against forestomach and skin carcinogenesis and warrantsthe identification and isolation of active compounds responsiblefor its anticancer effects, which may provide the lead for thedevelopment of antitumor agents.     

Adaptogenic activity of a novel withanolide-free aqueous fraction from the roots of Withania somnifera Dun. (Part II)

In the Indian traditional system of medicine Withania somnifera Dun. is widely regarded as the Indian Ginseng. A new withanolide-free hydrosoluble fraction was isolated from the roots of Withania somnifera Dun. and was evaluated for putative antistress activity against a battery of tests to delineate the activity of this fraction. The latter fraction exhibited significant antistress activity in a dose-related manner (Singh et al., 2001) and was further studied against chemical and physical induced stress in rats and mice. The extract of Withania somnifera root (a commercial preparation available locally) was also used to compare the results. A preliminary acute toxicity study in mice showed a good margin of safety with a high therapeutic index.     

Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera

Objective To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines. Methods First, compounds were retrieved from the PubChem database and predicted for their druggability using the MolSoft web server, and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity, hepatotoxicity, arrhythmia, myocardial infarction, and nephrotoxicity using ADVERpred. Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using AutoDock vina by PyRx 0.8 version. The stability of compound-protein interactions was checked by molecular dynamic (MD) simulation using Schrodinger Desmond software. Results Based on the druggable and nontoxic profile, nine compounds were selected. Among them, Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein (glycosylation site) and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns. Withanone, which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication. Conclusion The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.     

Withanolides from Whitania aristata and their diuretic activity

Aim of the study

Withania aristata is an endemic plant used traditionally in Canary Islands as a diuretic. In this paper, we report on this pharmacological activity in several extracts of the dry vegetal material collected and the identification and diuretic activity of two withanolides, one of them previously not reported, isolated from the most active fraction.

Material and methods

Four Whitania aristata extracts at 100 mg/kg were orally administered to laboratory animals to evaluate their diuretic activity. From the most active fraction, two withanolides were isolated. Both and a mixture of them at 5 and 10 mg/kg were analyzed too as diuretics. Water excretion rate and content of Na⁺ and K⁺ electrolytes were measured in the urine of saline-loaded animals.

Results

Whitania aristata water fraction, the two withanolides and the mixture of these compounds displayed high diuretic activity, with a significant excretion of sodium and potassium ions in laboratory animals.

Conclusions

This research supports the ethno-medicinal use of Whitania aristata as diuretic. This activity seems to be associated to the presence of a new type of natural diuretic agents, such as withaferin A and witharistatin.     

催眠睡茄植株再生体系的建立

目的:建立和优化催眠睡茄植株再生体系。方法:以催眠睡茄的叶片作为外植体,探讨不同植物生长物质对愈伤组织诱导,丛生芽分化以及试管苗生根的影响。结果和结论:愈伤组织诱导的最佳培养基是MS+1.0 mg.L-12,4-D+0.1mg.L-1KT;丛生芽诱导的最优培养基是MS+1.0 mg.L-16-BA+0.1 mg.L-1NAA,试管苗生根诱导最优培养基为1/2MS+0.5 mg.L-1NAA;在珍珠岩-腐殖土(1∶1)的基质中,再生植株室外移栽成活率达到92%。     

WITHANIA SOMNIFERA ROOT EXTRACT IN THE REGULATION OF LEAD-INDUCED OXIDATIVE DAMAGE IN MALE MOUSE

The importance of Withania somnifera root extract in the regulation of lead toxicity with special reference to lipid peroxidative process has been investigated in liver and kidney tissues. While lead treatment (0.5 mg kg(-1)body wt. day(-1)for 20 days) enhanced hepatic and renal lipid peroxidation (LPO), administration of plant extract in the doses of 0.7 g kg(-1)and 1.4 g kg(-1)body wt. day(-1)along with equivalent doses of lead acetate for 20 days significantly decreased LPO and increased the activities of antioxidant enzymes, viz., superoxide dismutase (SOD) and catalase (CAT), thus retaining normal peroxidative status of the tissues. We suggest that the ameliorating role of root extract of W. somnifera in the lead intoxicated mice could be the result of its antiperoxidative action.     

The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro

Using a validated explant model of in vitro cartilage damage, the effects of aqueous extracts of Withania somnifera (Ashwagandha) root and glucosamine sulphate (GlcS) were tested on the levels of nitric oxide (NO) and glycosaminoglycans (GAGs) secreted by knee cartilage from chronic osteoarthritis (OA) patients. W. somnifera extracts significantly decreased NO release by explants from one subset of patients (antiinflammatory response) and significantly increased levels of NO and GAGs released by explants from the second subset ('non-responders'). This is the first study showing direct, statistically significant, antiinflammatory effects of W. somnifera on human OA cartilage. It also confirmed that glucosamine sulphate exhibited statistically significant, antiinflammatory and chondroprotective activities in human OA cartilage. However, these beneficial effects of GlcS were observed in cartilage explants from 50% of patients tested ('responders'). In contrast, glucosamine significantly increased secretion of NO but not GAGs in explants from the second subset of OA patients ('non-responders'). Cartilage explants from the 11 OA patients gave differential responses to both drugs. Patient samples which responded to the antiinflammatory effects of W. somnifera did not always give a similar response to glucosamine, and vice versa. Thus, this in vitro model of human cartilage damage provides qualitative and statistically significant, quantitative pre-clinical data on antiinflammatory and chondroprotective activities of antiarthritic drugs.     

A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction

Many developed countries are experiencing a rapidly “greying” population, and cognitive decline is common in the elderly. There is no cure for dementia, and pharmacotherapy options to treat cognitive dysfunction provide limited symptomatic improvements. Withania somnifera (Ashwagandha), a popular herb highly valued in Ayurvedic medicine, has often been used to aid memory and cognition. This systematic review thus aimed to evaluate the clinical evidence base and investigate the potential role of W. somnifera in managing cognitive dysfunction. Using the following keywords [withania somnifera OR indian ginseng OR Ashwagandha OR winter cherry] AND [brain OR cognit* OR mental OR dementia OR memory], a comprehensive search of PubMed, EMBASE, Medline, PsycINFO and Clinicaltrials.gov databases found five clinical studies that met the study's eligibility criteria. Overall, there is some early clinical evidence, in the form of randomized, placebo‐controlled, double‐blind trials, to support the cognitive benefits of W. somnifera supplementation. However, a rather heterogeneous study population was sampled, including older adults with mild cognitive impairment and adults with schizophrenia, schizoaffective disorder, or bipolar disorder. In most instances, W. somnifera extract improved performance on cognitive tasks, executive function, attention, and reaction time. It also appears to be well tolerated, with good adherence and minimal side effects.     

In vivo,effect of herb (Withania somnifera) on immunomodulatory and antioxidative potential of milk in mice

Eighteen healthy male Swiss albino mice of specific weight (25–30g) were randomly divided into three groups of six animals each and given specific diets for a period 28 days. Group A was given normal synthetic diet (NSD) and milk; Group B: NSD and Withania somnifera (WS) extract (0.3%) and Group C: NSD supplemented with milk and WS extract (0.3%). The phagocytic activity of peritoneal macrophages and Immunoglobulin G (lgG) level in mice serum increased significantly in comparison to control group in WS-supplemented groups. The lymphocyte proliferation index did not alter significantly (P < 0.05) in supplemented groups after a period of 28 days. Group B and C showed significantly higher reduced glutathione level and significantly lowered (P < 0.05), carbonyl protein and thiobarbituric acid reactive substances in liver and red blood cells lysates as compared to control. This finding indicated that aqueous extract of WS is able to enhance immunomodulatory and antioxidative properties of milk.     

Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun.

The practitioners of the traditional Indian system of medicine regard Withania somnifera Dun. as the 'Indian ginseng'. A new withanolide-free aqueous fraction was isolated from the roots of this plant and was evaluated for putative antistress activity against a battery of tests such as hypoxia time, antifatigue effect, swimming performance time, swimming induced gastric ulceration and hypothermia, immobilization induced gastric ulceration, autoanalgesia and biochemical changes in the adrenal glands. This bioactive fraction exhibited significant antistress activity in a dose-related manner in all the parameters studied. The extract of Withania somnifera root (a commercial preparation available locally) was used to compare the results. A preliminary acute toxicity study in mice showed a good margin of safety.