Phenyl Propanoid 1’s-1′-Acetoxychavicol Acetate Protects Against Testosterone-Induced Alopecia by Inhibiting Nadph Oxidase

Androgenetic alopecia is induced by testosterone-mediated anagen-to-catagen transition and matrix keratinocyte apoptosis in hair follicle cells. Activation of Nox isozymes is involved in testosterone-mediated keratinocyte apoptosis, leading to androgenetic alopecia. This indicates that Nox isozymes can serve as therapeutic targets for androgenic alopecia. We screened 38 compounds to evaluate their ROS-inhibition efficacy and found that 1'S-1'-acetoxychavicol acetate (ACA, 26), a natural compound isolated from Alpinia galanga (L.) Willd. (Zingiberaceae), exhibits inhibitory activity on Nox isozymes. Nox inhibition by ACA suppressed testosterone-dependent H2O2 generation and cell death in keratinocytes. Incubation with ACA in human hair follicle culture mitigated testosterone-dependent growth suppression of hair. To validate the function of ACA in androgenic alopecia, we applied ACA locally on the dorsal skin in an androgenetic alopecia model of C57BL/6 mice, leading to suppression of testosterone-induced hair loss in a dose-dependent manner.