Dihydromethysticin is a kavalactone originally isolated from P. methysticum (kava-kava) that has diverse biological activities, including efflux transporter inhibitory, antinociceptive, and neuroprotective properties.1,2 Dihydromethysticin is a P-glycoprotein (P-gp) inhibitor that increases uptake of the P-gp substrate calcein AM by 50% in P388 mouse leukemia cancer cells overexpressing P-gp when used at a concentration of 54.6 μM.3 Dihydromethysticin (275 mg/kg) has analgesic activity, increasing the latency to tail withdrawal in the tail-flick assay in mice.1 It also decreases the infarct size in a mouse model of ischemia induced by microbipolar coagulation of the left middle cerebral artery (MCA) when administered at a dose of 10 mg/kg.2
1.Jamieson, D.D., and Duffield, P.H.The antinociceptive actions of kava components in miceClin. Exp. Pharmacol. Physiol.17(7)495-507(1990) 2.Backhauβ, C., and Krieglstein, J.Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodentEur. J. Pharmacol.215(2-3)265-269(1992) 3.Weiss, J., Sauer, A., Frank, A., et al.Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitroDrug Metab. Dispos.33(11)1580-1583(2005)