Abstract
BackgroundDermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles. Especially, DPCs determine the fate of hair follicle such as anagen to telogen transition and play a pivotal role in androgenic alopecia (AGA). This study was performed to elucidate the hair growth promoting effects of Polygonum multiflorum extract (PM extract) in cultured human DPCs and its underlying mechanisms.MethodsThe effects of PM extract on cultured DPCs were investigated. Cell viability and mitochondrial activity were measured by CCK-8 and JC-1 analysis, respectively. Western blotting, dot blotting, ELISA analysis, immunocytochemistry and real-time PCR analysis were also performed to elucidate the changes in protein and mRNA levels induced by PM extract. 3D cultured DPC spheroids were constructed for mimicking the in vivo DPs. The hair growth stimulatory effect of PM extract was evaluated using human hair follicle organ culture model.ResultsPM extract increased the viability and mitochondrial activity in cultured human DPCs in a dose dependent manner. The expression of Bcl2, an anti-apoptotic protein expressed dominantly in anagen was significantly increased and that of BAD, a pro-apoptotic protein expressed in early catagen was decreased by PM extract in cultured DPCs and/or 3D DPC spheroid culture. PM extract also decreased the expression of catagen inducing protein, Dkk-1. Growth factors including IGFBP2, PDGF and VEGF were increased by PM extract, revealed by dot blot protein analysis. We also have found that PM extract could reverse the androgenic effects of dihydrotestosterone (DHT), the most potent androgen. Finally, PM extract prolonged the anagen of human hair follicles by inhibiting catagen entry in human hair follicle organ culture model.ConclusionOur data strongly suggest that PM extract could promote hair growth by elongating the anagen and/or delaying the catagen induction of hair follicles through activation of DPCs.
Highlights
Dermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles
Polygonum multiflorum (PM) extract increased cell viability and mitochondrial activity of cultured human DPCs The effects of PM extract on cell viability and mitochondrial activity in cultured human DPCs were investigated using CCK-8 assay and JC-1 mitochondrial staining, respectively
Because the expression of androgen receptor (AR) in balding hair is much higher than that in nonbalding hair [42], our study suggests that PM extract could prevent androgen induced hair loss by reducing AR expression and preventing hair follicle miniaturization mediated by DHT which are thought to be the main cause of androgenic alopecia (AGA)
Summary
Dermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles. Hair follicles undergo three stages of the hair growth cycle called anagen, catagen, and telogen, which corresponds to the growing, regressing, and resting phases, respectively. Among various cell types that organize the hair follicle, dermal papilla cells (DPCs) play key roles in proliferation and differentiation of hair follicles and controlling hair cycle in each phase [1]. Transition of hair cycles is controlled by DPCs. Transition of hair cycles is controlled by DPCs Secreted proteins such as transforming growth factors (TGF) β1, TGF β2, and dickkopf (DKK-1) are known to induce transition from anagen to telogen [4]. BAD protein, another member of bcl family, is known to induce apoptosis [7]
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