Jiawei Erzhiwan ameliorates androgenetic alopecia by regulating the SIRT1/JNK/p38 MAPK pathway

Androgenetic alopecia (AGA) is a type of hair loss. Our previously study showed AGA ameliorating capability of water extract of an herbal prescription, “Jiawei Erzhiwan” (WJWE), which was derived from the traditional formula “Erzhiwan”. However, the underlying mechanisms is still unknown. In this study, the phytochemical ingredients in WJWE were characterized via UPLC‒MS/MS analysis. The dihydrotestosterone (DHT)-induced murine model and dermal papilla cells (DPCs) assays were used to evaluate and elucidate the beneficial effects and mechanisms of WJWE on AGA. WJWE promoted hair growth and hair follicle regeneration in AGA mice, improved DPCs growth and dose-dependently protected DHT-reduced DPCs viability <i>in vitro</i> by stimulating the Wnt5A/β-Catenin pathway. Additionally, WJWE reduced DHT-induced oxidative stress in AGA model murine skin and DHT-treated DPCs. To elucidate the regulative mechanism, we found that WJWE treatment significantly and dose-dependently increased the expression of SIRT1 and reduced the phosphorylation of JNK and p38 MAPK in both DHT-treated DPCs and AGA model mice. And the application of EX527 (a SIRT1 inhibitor) could the effect of WJWE. Our study provided some evidences of WJWE on AGA treatment, by which SIRT1/JNK/p38 MAPK signaling pathway might be the major target.