Stauntonia hexaphylla Extract Ameliorates Androgenic Alopecia by Inhibiting Androgen Signaling in Testosterone-induced Alopecia Mice

Abstract

Background: Stauntonia hexaphylla has been a traditional folk remedy for alleviating fever and providing anti-inflammatory properties. Androgenetic alopecia (AGA) is the most common form mediated by the presence of the dihydrotestosterone (DHT). Objectives: In this study, we evaluated the effects of an extract of S. hexaphylla on AGA models and its mechanisms of action. Methods: We studied S. hexaphylla extract to evaluate 5α-reductase and androgen receptor (AR) levels, apoptosis, and cell proliferation in vitro and in vivo. In addition, paracrine factors for androgenic alopecia, such as transforming growth factor beta-1 (TGF-β1) and dickkopf-a (DKK-1), were examined. Apoptosis was investigated, and the evaluation of proliferation was examined with cytokeratin 14 (CK-14) and proliferating cell nuclear antigen (PCNA). Results: In human follicular dermal papilla cells, the 5α-reductase and AR were decreased following S. hexaphylla treatment, which reduced the Bax/Bcl-2 ratio. Histologically, the dermal thickness and follicle number were higher in the S. hexaphylla groups compared with the AGA group. In addition, the DHT concentration, 5α-reductase, and AR were decreased, thereby downregulating TGF-β1 and DKK-1 expression and upregulating cyclin D in S. hexaphylla groups. The numbers of keratinocyte-positive and PCNA-positive cells were increased compared to those in the AGA group. Conclusions: The present study demonstrated that the S. hexaphylla extract ameliorated AGA by inhibiting 5α-reductase and androgen signaling, reducing AGA paracrine factors that induce keratinocyte (KC) proliferation, and inhibition apoptosis and catagen prematuration.