Abstract

The hair growth cycle consists of the anagen, catagen, and telogen phases, and hair follicle dermal papilla (HDP) cells of human hair play a role in the initiation and maintenance of the anagen phase. Reduction in HDP cells contributes to hair loss; however, the limited treatment options are associated with negative side effects. Therefore, a naturally derived substance with hair loss-preventing properties is needed. We investigated the hair growth-stimulating activities of Plantago asiatica L. extract (PAE) and its molecular mechanism in HDP cells. Cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide solution. Relative mRNA and protein expression levels of hair growth factors were determined using quantitative real-time polymerase chain reaction and western blotting, respectively. Additionally, a tube formation assay was performed in human umbilical vein endothelial cells (HUVEC). Plantago asiatica L. extract significantly increased the cell proliferation and expression of hair growth factors, including keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2) and MYC, in HDP cells. Moreover, PAE led to the accumulation of β-catenin by promoting the phosphorylation of glycogen synthase kinase-3 beta (GSK-3β) at Ser9 and cAMP response element-binding protein (CREB) at Ser133 via phosphorylation of extracellular signal-regulated kinase (ERK) (Thr202/Tyr204). PAE also increased tube formation in HUVECs, which promoted angiogenesis for the anagen phase. Plantago asiatica L. extract amplified tube formation and production of growth factors (KGF, VEGF) via the activation of GSK-3β/β-catenin and mitogen-activated protein kinase (MAPK)/CREB signaling pathways, demonstrating its potential to safely promote hair growth by inducing the anagen phase.

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