<b>Zhimo herbal extract powder ameliorates androgenic alopecia by regulating the SIRT1/JNK/p38 MAPK pathways</b>

<b>Background:</b> Androgenetic alopecia (AGA) is the most widespread type of hair loss. Zhimo herbal extract powder (ZMHE) is an aqueous extract of an herbal prescription, derived from the traditional formula “Erzhi Wan”, which has an ameliorative effect on AGA. However, few underlying mechanisms have been explored.<b>Methods:</b> In this study, the phytochemical characteristics of ZMHE were compared with those of six standard chemicals 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 ZMHE on AGA.<b>Results: </b>ZMHE contained 1.4 mg/g salidroside, 0.791 mg/g hydroxysafflor yellow A, 0.838 mg/g 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside, 0.252 mg/g quercitrin, 0.085 mg/g resveratrol, and 0.449 mg/g wedelolactone. ZMHE promoted hair growth and hair follicle regeneration in AGA mice, improved DPC growth and dose -dependently restored DHT-reduced DPCs viability <i>in vitro</i> by stimulating the expression of Wnt5A and β-Catenin. To elucidate the anti-AGA mechanism, we first determined the DPPH-released free radical scavenging activity of ZMHE. Additionally, ZMHE attenuated DHT-induced high levels of ROS, MDA and COX-2, simultaneously restrored low contents of GSH, SOD and HO-1 in DHT -treated DPCs and AGA model murine skin. ZMHE 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. The application of the SIRT1 inhibitor selisistat (EX527), partially inhibited the protective effect of ZMHE in AGA mice.<b>Conclusions: </b>Overall, our study provides positive evidence that ZMHE is beneficial for AGA treatment and that the SIRT1/JNK/p38 MAPK pathway might be the major target of the ZMHE-regulated signaling network.