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.
