Compound glycyrrhizin promotes hair growth in C57BL/6 mice by regulating the Wnt/β-catenin pathway

Background: Androgenetic alopecia (AGA), a kind of nonscarring baldness, is an androgen-dependent autosomal dominant polymorphism. Compound glycyrrhizin (CG), a compound preparation-containing glycyrrhizin, aminoacetic, and methionine, has been used to treat alopecia areata. Objectives: Our study aimed to explore the role of CG in hair regrowth in testosterone-induced AGA mouse model and the proliferation of human hair dermal papilla cells (HDPCs) and the related molecular mechanisms. Methods: The AGA mouse model was established through the injection of testosterone. The in vivo therapeutic effects of CG on AGA were assessed by detecting skin color changes, hair growth time, average hair length, and histological score. Human HDPCs after CG treatment were subjected to CCK-8 assay to evaluate cell proliferation. The impacts of CG on growth factor expression and the Wnt/β-catenin signaling in mouse dorsal skins and HDPCs were determined by undertaking western blotting, reverse transcription-quantitative polymerase chain reaction, and immunofluorescence staining. The Wnt/β-catenin pathway inhibitor XAV939 was used to validate the beneficial role of Wnt/β-catenin pathway activation in CG-mediated hair growth. Results: Our results showed that CG facilitated new hair growth and increased hair follicle numbers on the depilated dorsal area of the model mice. Furthermore, CG administration upregulated p-GSK-3β, β-catenin, cyclin D1, Axin2, LEF1, fibronectin, and survivin levels in the dorsal skins of model mice. In vitro assays revealed that CG promoted cell proliferation, elevated the mRNA levels of growth factors-related genes (insulin-like growth factors-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF)), and increased p-GSK-3β, β-catenin, cyclin D1, Axin2, LEF1, fibronectin, and survivin protein levels in HDPCs. Importantly, XAV939 treatment debilitated the promotion of CG on hair regrowth in model mice and human hair dermal papilla cell (HPDC) proliferation. Conclusion: The beneficial role of CG in hair regrowth in AGA mice and HDPC cell proliferation depends on the Wnt/β-catenin pathway activation and the subsequent growth factor production in hair follicles. These results imply the potential of CG in the treatment of AGA.