Withanone (Synonyms: NSC 179884)

Withanone is a phytochemical that has been found in W. somnifera and has diverse biological activities.^1,2,3 It inhibits the protein-protein interaction between human angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein receptor-binding domain (IC₅₀ = 0.33 ng/ml).¹ Withanone (10 µg/ml) protects against DNA damage, oxidative stress, and premature senescence induced by the industrial contaminant methoxyacetic acid in TIG-1 human fibroblasts.² In vivo, withanone (5-20 mg/kg) decreases brain levels of amyloid-β 1-42 (Aβ42), malondialdehyde (MDA), TNF-α, IL-1β, and IL-6, increases brain levels of acetylcholine, and improves cognitive function in a rat model of streptozotocin-induced sporadic Alzheimer’s disease.³

1.Balkrishna, A., Pokhrel, S., Singh, H., et al.Withanone from Withania somnifera attenuates SARS-CoV-2 RBD and host ACE2 interactions to rescue spike protein induced pathologies in humanized zebrafish modeDrug Des. Devel. Ther.151111-1133(2021) 2.Priyandoko, D., Ishii, T., Kaul, S.C., et al.Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolitePLoS One6(5)e19552(2011) 3.Pandey, A., Bani, S., Dutt, P., et al.Multifunctional neuroprotective effect of withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunctionCytokine102211-221(2018)