Withaferin A
(4β,5β,6β,22R)-4,27-dihydroxy-5,6:22,26-diepoxyergost-2-en-1-one
Chemical Class
Withanolide (Steroidal Lactone)
Molecular Formula
C28H38O6
Molecular Weight
470.59 g/mol
Half-Life
Plasma half-life approximately 1.5–2 hours in preclinical studies. Tissue accumulation observed in liver and brain.
Bioavailability
Moderate oral bioavailability. Shows dose-dependent plasma levels in animal models. Tissue distribution includes brain, indicating blood-brain barrier penetration. Metabolised primarily via hepatic glucuronidation.
Known Effects
Anti-inflammatory, anticancer, immunomodulatory, neuroprotective, and adaptogenic activity. Demonstrates potent antitumour activity in breast, ovarian, and pancreatic cancer models.
Mechanism of Action
Potent NF-κB pathway inhibitor. Binds to intermediate filament protein vimentin, causing cytoskeletal disruption in cancer cells. Inhibits COX-2 expression. Modulates JAK/STAT3 signalling. Induces apoptosis via caspase activation. Demonstrates GABA-A receptor modulation contributing to anxiolytic effects.
Safety Data
No human toxicology data at therapeutic doses. Animal studies indicate low toxicity at standard doses. Potential abortifacient activity reported in traditional use. Further safety studies needed.