Cepharanthine induces the proliferation of human dermal papilla cells and stimulates vascular endothelial growth factor expression through increased intracellular calcium mobilization and hypoxia‐inducible factor activation

Background Cepharanthine (CEP), a compound extracted from the vine Stephania cephalantha, is commonly prescribed to treat alopecia areata; however, the scientific evidence for its efficacy is limited. Aim To investigate the effect of CEP and its structural analogues on human hair growth in vitro. Methods The effects of CEP and three of its structural analogues on the proliferation of human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs) were investigated. Their effects on vascular endothelial growth factor (VEGF) expression were also assessed by real-time PCR. Activation of pathways leading to VEGF expression, such as intracellular Ca2+ mobilization and hypoxia-inducible factor (HIF) expression, was also characterized. Results CEP and two of its structural analogues significantly stimulated the growth of hDPCs but not hORSCs. Moreover, CEP and all three structural analogues significantly induced the expression of VEGF in hDPCs. CEP increased the intracellular Ca2+ concentration in hDPCs. CEP also increased the expression of HIF-1α and HIF-2α and induced the expression of HIF-responsive genes in hDPCs, even under normoxia. Conclusions These results suggest that CEP and its structural analogues have the potential to restore hair growth by promoting the proliferation of hDPCs and increasing their expression of VEGF.