Berberine promotes hair growth by targeting Axin2 and activating Wnt/β-catenin pathway

Abstract

Background: Androgenetic alopecia (AGA) is the most common type of hair loss, with high incidence of comorbidities such as polycystic ovary syndrome (PCOS), metabolic syndrome, insulin resistance and cardiovascular diseases. Berberine (BBR) has been widely used clinically to treat diarrhea in China for a long time. Although recent studies have revealed its therapeutic potential in comorbidities of AGA, there are few reports on its regulatory effects on hair growth.

Purpose: To explore the effects of BBR on hair loss and its mechanism.

Methods: Human dermal papilla cells (hDPCs), normal and miniaturized hair follicles (HFs) were employed to evaluate the impact of BBR on hair growth in vitro. Depilation-induced hair growth mouse model was used to find the optimum concentration of BBR in vivo. Network pharmacology, RNA sequencing, cell transfection and reporter gene assay, immunohistochemistry, and molecular docking verification were used to explore the molecular mechanisms.

Results: These models revealed that BBR enhanced the proliferation of hDPCs, increased the length of both normal and miniaturized HFs, and prolonged the anagen phase. In the depilation-induced hair growth mouse model and histological staining, BBR treatment significantly accelerated hair growth, facilitated the transition to the anagen phase, and prolonged its duration. Mechanistic studies confirmed that BBR promoted hair growth through regulating cell cycle, mediated by targeting Axin and activating the Wnt/β-catenin pathway. Importantly, knockdown of Axin2 reduced BBR's ability to enhance hDPCs proliferation.

Conclusions: These results suggested that BBR promotes hair growth by targeting Axin2 and activating Wnt/β-catenin pathway, presenting a promising therapeutic avenue for hair loss treatment.

Keywords: Axin2; Berberine; Hair growth; Wnt/β-catenin pathway.