Xiaozhi Yufa decoction ameliorates androgenetic alopecia through inhibition of MAPK signaling and regulation of lipid metabolism

Yiyu Guo¹Dengke Yang²Jie Wu²Yu Lu²Jianping Qin²Lanlan Huang²Fengrui Zhang²Xiaomei Zhou²Jianzhou YE^1*

• ¹Nanjing University of Chinese Medicine, Nanjing, China
• ²Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, China

Background: Androgenetic alopecia represents the most common form of progressive hair loss, with current treatments showing limitations in efficacy or tolerability. Xiaozhi Yufa decoction (XZYFD), a Traditional Chinese Medicine formulation composed of 13 herbal medicines, has shown clinical potential in treating hair loss. Methods: Network pharmacology analysis identified active compounds and potential targets of XZYFD, with molecular docking evaluating compound-target interactions. A testosterone propionate-induced mouse model was established to assess XZYFD's therapeutic efficacy. Treatment effects were evaluated through hair regrowth assessment, histological examination, serum biochemical analysis, and molecular pathway investigation. Results: Network pharmacology identified 57 overlapping targets between XZYFD and androgenetic alopecia, with enrichment in MAPK signaling and lipid metabolism pathways. In vivo experiments demonstrated that XZYFD dose-dependently promoted hair regrowth and restored follicular morphology. Treatment significantly improved hormonal profiles, reduced serum lipid levels, and suppressed inflammatory markers. XZYFD effectively inhibited androgen metabolism and suppressed 2 activation of MAPK signaling and SREBP-1-mediated lipid metabolism pathways, as confirmed through gene expression, protein analysis, and immunohistochemistry. Conclusions: XZYFD ameliorates androgenetic alopecia through simultaneous modulation of androgen metabolism, MAPK signaling, and SREBP-1-mediated lipid metabolism, with potential advantages for patients with metabolic dysfunction.