Avicequinone C Isolated from Avicennia marina Exhibits 5α-Reductase-Type 1 Inhibitory Activity Using an Androgenic Alopecia Relevant Cell-Based Assay System

Avicennia marina (AM) exhibits various biological activities and has been traditionally used in Egypt to cure skin diseases. In this study, the methanolic heartwood extract of AM was evaluated for inhibitory activity against 5 alpha-reductase (5 alpha-R) [E. C. 1.3.99.5], the enzyme responsible for the over-production of 5 alpha-dihydrotestosterone (5 alpha-DHT) causing androgenic alopecia (AGA). An AGA-relevant cell-based assay was developed using human hair dermal papilla cells (HHDPCs), the main regulator of hair growth and the only cells within the hair follicle that are the direct site of 5 alpha-DHT action, combined with a non-radioactive thin layer chromatography (TLC) detection technique. The results revealed that AM is a potent 5 alpha-R type 1 (5 alpha-R1) inhibitor, reducing the 5 alpha-DHT production by 52% at the final concentration of 10 mu g/mL. Activity-guided fractionation has led to the identification of avicequinone C, a furanonaphthaquinone, as a 5 alpha-R1 inhibitor with an IC50 of 9.94 +/- 0.33 mu g/mL or 38.8 +/- 1.29 mu M. This paper is the first to report anti-androgenic activity through 5 alpha-R1 inhibition of AM and avicequinone C.