The Sunlight Experiment

Compound Monograph

Withaferin A

Withaferin A — the principal steroidal lactone (withanolide) of ashwagandha and the focus of its anticancer research, a cytotoxic compound studied for tumour apoptosis, NF-κB suppression, and HSP90 inhibition.

Work in progress

Classification

Withaferin A is a steroidal lactone (withanolide), part of the terpenoids class. The largest class of plant compounds, built from five-carbon isoprene units — the essential-oil aromatics, resins, bitter principles, saponins, and plant sterols.

Terpenoids Sterols & Steroids

Where Does It Come From? (1)

Withaferin A is a naturally occurring steroidal lactone (withanolide), found in Ashwagandha. It is flagged as moderately toxic.

Ashwagandha Withania somnifera

Research & Evidence

Withaferin A is the best-known steroidal lactone (withanolide) in ashwagandha root and is regarded as the single most significant component behind the herb’s anticancer activity 1,2,5Reference 1Bone K · 2013Principles and Practice of PhytotherapyReference 2Bone · 2003A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual PatientReference 5Turrini E et al. · 2016Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia CellsView study →.

The ashwagandha monograph in this database attributes the following to withaferin A and the withanolides:

  • Anticancer — ashwagandha’s antitumoral activity is mediated through regulation of cell-cycle proliferation, increased tumour apoptosis, inhibition of angiogenesis, suppression of NF-κB, and increased immune activity, and much of the research underlying these mechanisms is on withaferin A 1,2,3Reference 1Bone K · 2013Principles and Practice of PhytotherapyReference 2Bone · 2003A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual PatientReference 3Vyas AR · 2014Molecular targets and mechanisms of cancer prevention and treatment by withaferin A, a naturally occurring steroidal lactone. The withanolides potentiate apoptosis, inhibit invasion, and suppress NF-κB-regulated gene expression 4Reference 4Ichikawa H et al. · 2006Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression, and withaferin A produces cytotoxic and cytostatic effects on human T-leukemia cells 5Reference 5Turrini E et al. · 2016Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia CellsView study →. Activity has also been characterised in B-cell lymphoma 6Reference 6McKenna MK et al. · 2015Anti-cancer activity of withaferin A in B-cell lymphoma and pancreatic cancer, where withaferin A targets the chaperone protein HSP90 7Reference 7Yu Y et al. · 2010Withaferin A targets heat shock protein 90 in pancreatic cancer cells.
  • Anti-inflammatory — withaferin A inhibits IL-1β production in dendritic cells by regulating NF-κB and NLRP3 inflammasome activation induced by H. pylori, which is of interest in preventing H. pylori-induced gastric cancer 8Reference 8Kim J et al. · 2015Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1β in Dendritic Cells by Regulating NF-κB and NLRP3 Inflammasome ActivationView study →.

Toxicity & Safety

This page concerns isolated withaferin A, not whole ashwagandha root. The parent herb is noted in the source as gentle and highly tolerable — used even in children during convalescence — with the main practical caution being possible heavy-metal (lead) contamination of material grown in some regions 1Reference 1Bone K · 2013Principles and Practice of Phytotherapy. Isolated withaferin A is a different matter: it is a cytotoxic withanolide investigated specifically as an anticancer agent, producing cytotoxic and cytostatic effects on tumour cells and driving apoptosis and cell-cycle arrest 5Reference 5Turrini E et al. · 2016Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia CellsView study →. For that reason it is flagged here as moderate rather than as a benign dietary constituent — its activity profile is that of a pharmacologically active cytotoxic compound. The cautions described in the source are for the whole-root preparations rather than for the purified molecule.

References

  1. Bone K, Mills S. (2013). Principles and Practice of Phytotherapy. Elsevier Health, China. (Pg. 949–959).
  2. Bone, K. (2003). A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual Patient. Edinburgh: Churchill Livingstone.
  3. Vyas AR, Singh SV. (2014). Molecular targets and mechanisms of cancer prevention and treatment by withaferin A, a naturally occurring steroidal lactone. AAPS J, 16, 1–10.
  4. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. (2006). Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther, 5, 1434–1445.
  5. Turrini E, Calcabrini C, Sestili P, Catanzaro E, De Gianni E, Diaz A, … Fimognari C. (2016). Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells. Toxins, 8(5), 147. doi:10.3390/toxins8050147
  6. McKenna MK, Gachuki BW, Alhakeem SS, Oben KN, Rangnekar VM, Gupta RC, Bondada S. (2015). Anti-cancer activity of withaferin A in B-cell lymphoma. Cancer Biol Ther, 16, 1088–1098.
  7. Yu Y, Hamza A, Zhang T, Gu M, Zou P, Newman B, Li Y, Gunatilaka AA, Zhan CG, Sun D. (2010). Withaferin A targets heat shock protein 90 in pancreatic cancer cells. Biochem Pharmacol, 79, 542–551.
  8. Kim J, Lee J, Kang M, Jeong Y, Choi J, Oh S, … Park J. (2015). Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1β in Dendritic Cells by Regulating NF-κB and NLRP3 Inflammasome Activation. Immune Network, 15(6), 269. doi:10.4110/in.2015.15.6.269