Identification of bioactive compounds from thai plant extracts with hair growth promoting activity on human hair dermal papilla cells

Abstract

Androgenic alopecia (AGA) is the major type of scalp hair loss caused by the over-production of 5 alpha-dihydrotestosterone (5 alpha-DHT) which is formed by the enzyme 5 alpha-reductase (5 alpha-R) using testosterone (T) as the substrate. In this study, the main focus was on identifying new natural 5 alpha-R inhibitors specifically for treating AGA. In order to do so, an AGA relevant cell-based assay using human hair dermal papilla cells (HHDPCs) combined with non-radioactive thin layer chromatography (TLC) detection was developed and used for screening Thai medicinal plant extracts possessing inhibitory activities of 5 alpha-reductase type 1 (5 alpha-R1), the isoform of the enzyme found to be expressed by HHDPCs. Among forty-one extracts screened, the methanolic heartwood extract of Avicennia marina (AM) was found to be the only sample that exhibited significant 5 alpha-R1 inhibitory activity with the IC50 value of 9.21 μg/ml. In addition, the AM extract also exhibited anti-androgenic activity through a significant up-regulation of vascular endothelial growth factor (VEGF) in androgens treated HHDPCs. This growth factor is known to induce the proliferation and differentiation of hair matrix cells during the anagen/growth phase of the hair cycle, leading to hair growth. Further identification of the active compound(s) in the AM extract by activity-guided fractionation revealed that the active 5 alpha-R1 inhibitor was actually a furano-naphthoquinone compound, namely Avicequinone C (IC50 of 9.94 μg/ml or 38.8 μM). However, the significant up-regulation of VEGF was not clearly observed by Avicequinone C alone but rather when it was combined with Avicenol C and an unidentified compound in faction ‘4’ obtained from the crude extract of AM. These results suggested that anti-androgenic activity of AM was due to a synergistic effect of a few compounds present in its methanolic extracts.