Moracin M promotes hair regeneration through activation of the WNT/β-catenin pathway and angiogenesis.

Hair follicle growth depends on the intricate interaction of cells within the follicle and its vascular supply. Current FDA-approved treatments like minoxidil have limitations, including side effects and the need for continuous use. Moracin M, a compound from Moraceae family, was investigated for its effects on hair growth and vascular regeneration. In our study, Moracin M significantly increased cell proliferation in human dermal papilla cells (hDPCs) during both the anagen and catagen phases and promoted cell migration in human umbilical vein endothelial cells (HUVECs) without cytotoxicity at concentrations up to 50 µM. Mechanistic analysis revealed that moracin M enhanced Wnt3a, GSK-3β phosphorylation and increased non-phospho β-catenin levels, activating Wnt signaling and upregulating transcription factors LEF, TCF, and AXIN2. This resulted in elevated levels of growth factors VEGF, FGF2, KGF, HGF and MYC in hDPCs, effects comparable to those of minoxidil. Additionally, moracin M significantly increased protein and mRNA levels of VEGF, FGF2, and KGF in hDPCs under IFN-γ-induced inflammatory conditions. Moracin M treatments also resulted in notable wound width reductions in a dose-dependent manner. Further investigation showed that moracin M stimulated MMP-2 and MMP-9 expression. These findings indicate that moracin M significantly enhances hair growth through the promotion of cell proliferation and angiogenesis, particularly via the activation of the Wnt signaling pathway in dermal papilla cells, presenting it as a promising therapeutic alternative to current treatments.