Salvianolic acid B ameliorate alopecia by simultaneously targeting Wnt/β-catenin and mTORC2/Akt signaling.

Abstract

BACKGROUND: Alopecia is a prevalent clinical condition with currently limited therapeutic options. Salvianolic acid B (Sal B) has demonstrated promising regenerative properties across various disease models. However, its potential role in the treatment of alopecia and the underlying mechanisms remain largely unexplored. OBJECTIVE: To elucidate the role and mechanisms of Sal B in hair regeneration, we evaluated its effects on hair loss model in vivo and in vitro, and integrated multi-omics analysis. METHODS: We performed reverse molecular docking screening using the LRP6 receptor (PDB: 7NAM) to identify Sal B as a top candidate. Network pharmacology and molecular docking were used to predict target genes and binding affinity. Sal B was treated with cultured DPCs and hair follicles to investigate its effects on DPC proliferation. In vivo efficacy was evaluated in murine alopecia and AGA. Integrated multi-omics analysis, complemented by Western blot and PCR, was employed to elucidate the key signaling pathways. RESULTS: Sal B bound strongly to LRP6 and promoted DPC proliferation, migration, and stemness. It enhanced hair shaft elongation in vitro and stimulated hair regeneration in mice, outperforming minoxidil in AGA models. Multi-omics analyses revealed enrichment in mTOR signaling, matrix metalloproteinases (MMPs), and MAPK pathways. Sal B activated mTORC2/Akt signaling, upregulated RICTOR, downregulated DEPTOR, and enhanced phosphorylation of Akt and GSK-3β, leading to β-catenin stabilization. It also increased expression of MMP9, MMP3, MMP1, and activated ERK and p38. CONCLUSION: Sal B promotes hair regeneration through dual activation of the Wnt/β-catenin and mTORC2/Akt pathways, and upregulation of MMPs and MAPKs.