WITHANIA SOMNIFERA
TAXONOMIC CLASSIFICATION
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COMMON NAMES: Winter-cherry, Winter Cherry, Withania, Rennet, Poisonous gooseberry, Ashwagandha, Indian ginseng and Poison gooseberry
BOTANICAL DESCRIPTION
Withania somnifera is a perennial, evergreen shrub up to 2 meters tall with silver-gray, tomentose branches, nearly hairless green elliptic leaves, and small green bell-shaped flowers, producing orange-red berries with rough, netted seeds, and has stout, fleshy roots with a strong odor and bitter taste.
ETHNOBOTANICAL USES
Ashwagandha is traditionally used to treat a variety of conditions including emaciation in children, old age effects, rheumatism, leucoderma, constipation, insomnia, nervous breakdown, and goiter, and is also applied as a paste for inflammation, ulcers, and snake venom; Nagori Ashwagandha is considered the most potent, with the highest benefits derived from fresh powder.
PHYTOCHEMICAL COMPOSITION
Notable compounds include Withaferin A, viscosalactone B, 27-deoxywithaferin A, pubesenolide, jaborosalactone D 4b,27- dihydroxy-L-oxo-22R-witha-2,5,24-trienolide, 2,3-dihydrowithaferin A-3b-O-sulfate, withanolide A, and 27- hydroxywithanolide B. Primary and secondary metabolites identified in the fruits included mevalonic acid (MVA), 1-deoxy-D-xylulose-5-phosphate (DOXP), shikimic acid, phenylpropanoid, squalene, and tocopherol. The dominant withanolides include withanolide D and withaferin A, which are known for their antitumor, anti-inflammatory, and immunosuppressant properties. They are also potent antioxidants, contributing to the neuroprotective effects of the plant extract.
CHEMICAL STRUCTURE
PHARMACOLOGICAL ACTIVITIES
IMMUNE SYSTEM EFFECTS
Withania somnifera's withanolides improve macrophage activation, phagocytosis, and lysosomal activity, exhibiting antistress properties and improving learning and memory in rats. They inhibit murine spleen cell proliferation, reduce inflammation-stimulated alpha-2 macroglobulin synthesis, and prevent myelosuppression in mice. Clinically, a 6 mL root extract increased CD4 expression and cytokine levels.
ANTI-DIABETIC ACTIVITY
Ancient formulations like Dianix and Trasina, along with Withania somnifera (WS) root powder, have shown strong antidiabetic effects. WS significantly improved insulin sensitivity and reduced blood glucose, with leaf extracts proving more effective than roots. In diabetic rats, WS extracts restored glucose levels and enhanced antioxidant defenses. Withaferin-A shows anti-glycating and anti-inflammatory effects.
CARDIO-PROTECTIVE ACTIVITY
Withania somnifera has shown cardioprotective effects in animal models, improving cardiovascular health at doses of 30, 60, and 90 mg/kg/day. It provides cardio protection against doxorubicin-induced toxicity by activating the Nrf2 transcription factor, which reduces cardiomyocyte apoptosis. Standardized WS extracts at 300 mg/kg prevent doxorubicin-induced cardiotoxicity and normalize several biochemical markers.
IMMUNOMODULATORY ACTIVITY
Ashwagandha extracts have shown significant immunomodulatory effects in Swiss albino mice by increasing white blood cell and platelet counts, reducing DTH reactions, and mitigating cyclophosphamide-induced immunosuppression. They also provide cyto-protection against lead toxicity, enhance antibody responses, and improve macrophage phagocytosis. Additionally, WS demonstrated dose-dependent immunomodulatory activity in Ehrlich ascites tumor-bearing mice.
ANTI-INFLAMMATORY ACTIVITY
Withania somnifera has shown significant anti-inflammatory effects across various models, including reducing neutrophil infiltration and edema in inflammatory bowel disease, mitigating symptoms of systemic lupus erythematosus, and protecting endothelial cells from inflammation. Withaferin-A, a key compound in WS, inhibits inflammatory pathways and reduces expression of inflammatory markers, and has shown efficacy in reducing arthritis inflammation when combined with other extracts.
ANTI-AMYOTROPHIC LATERAL SCLEROSIS (ALS)/ PRONTOTEMPORAL LOBAR DEGENERATION (FTLD) ACTIVITIES
The root extract of Withania somnifera reversed TDP-43 proteinopathy in a mouse model of ALS/FTLD, correcting cytoplasmic mislocalization. In the SOD1G93A mouse model, WS extracts provided protective effects by reducing glial activation, inducing autophagy, preventing NF-κB phosphorylation, and altering cytokine and chemokine expression.
TOXICOLOGICAL PROFILE
Withania somnifera is generally safe, with low toxicity reported. The LD50 values range from 432 mg/kg to over 2000 mg/kg across various extracts and administration routes. Specifically, total alkaloids had an LD50 of 465 mg/kg in rats, while alcoholic extracts showed higher LD50 values of 1750 ± 41 mg in mice. Withaferin A has an LD50 of about 80 mg/kg in mice. Other extracts, including withanolide-free and hydroalcoholic extracts, were non-toxic or had high LD50 values.
CLINICAL VALIDATED USES AND DRUG-DRUG INTERACTION
Not reported
REFERENCES
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