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A chalcone with diverse biological activities
Flavokawain A is a chalcone that has been found in P. methysticum and has diverse biological activities.1,2,3 It activates nuclear factor erythroid 2-related factor 2 (Nrf2) and heat shock factor 1 (Hsf1; EC50s = 14.1 and 7.9 ?M, respectively, in reporter assays), increases glutathione (GSH) levels, and protects against hydrogen peroxide-induced cytotoxicity in HepG2 cells.1 Flavokawain A (10 and 20 ?M) inhibits LPS-induced increases in inducible nitric oxide synthase (iNOS), COX-2, nitric oxide (NO), and prostaglandin E2 levels in RAW 264.7 macrophages.2 It induces apoptosis in T24 bladder cancer cells when used at a concentration of 12.5 ?g/ml.3 Flavokawain A (50 mg/kg) reduces tumor growth in an EJ bladder cancer mouse xenograft model.
1.Pinner, K.D., Wales, C.T.K., Gristock, R.A., et al.Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytesPharm. Biol.54(9)1503-1512(2016) 2.Kwon, D.-J., Ju, S.M., Youn, G.S., et al.Suppression of iNOS and COX-2 expression by flavokawain A via blockade of NF-κB and AP-1 activation in RAW 264.7 macrophagesFood Chem. Toxicol.58479-486(2013) 3.Zi, X., and Simoneau, A.R.Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in miceCancer Res.65(8)3479-3486(2005)
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