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

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.