avicequinone-c and Alopecia

Androgenic alopecia (AGA) is associated with an increased production of 5α-dihydrotestosterone (DHT) by steroid-5α-reductase (5α-R). Crude extracts from Avicennia marina (AM) and its active constituent, avicequinone C (AC), can inhibit 5α-R. We have, herein, explored the potential use of the AM extract and of AC as anti-AGA agents. To this end, we employed human dermal papilla cells (DPCs) isolated from AGA patients' hair that express 5α-R type-1 as well as the androgenic receptor (AR) at high levels. Our in vitro experiments revealed that the AM extract (10 μg/mL) and the AC (10 μM) exhibit multiple actions that interfere with the mechanism that causes AGA. Beside acting as 5α-R inhibitors, both preparations were able to inhibit either the DHT-AR complex formation or its translocation from the cytoplasm into the nucleus (the site of DHT's action). The treatments also increased the gene expression of growth factors in DPCs; these factors play important roles in the angiogenesis associated with hair growth. Moreover, the AM extract suppressed the apoptotic pathway, thereby postponing the initiation of the catagen phase. Taken together, our findings suggest that the AM extract and the AC could serve as natural sources for hair growth promotion and AGA treatment.

Topics: Alopecia; Avicennia; Dihydrotestosterone; Hair; Hair Follicle; Humans; Quinones

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 5α-reductase (5α-R) [E.C.1.3.99.5], the enzyme responsible for the over-production of 5α-dihydrotestosterone (5α-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 5α-DHT action, combined with a non-radioactive thin layer chromatography (TLC) detection technique. The results revealed that AM is a potent 5α-R type 1 (5α-R1) inhibitor, reducing the 5α-DHT production by 52% at the final concentration of 10 µg/mL. Activity-guided fractionation has led to the identification of avicequinone C, a furanonaphthaquinone, as a 5α-R1 inhibitor with an IC50 of 9.94 ± 0.33 µg/mL or 38.8 ± 1.29 µM. This paper is the first to report anti-androgenic activity through 5α-R1 inhibition of AM and avicequinone C.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; 5-alpha Reductase Inhibitors; Alopecia; Avicennia; Cells, Cultured; Dihydrotestosterone; Drug Evaluation, Preclinical; Hair; Humans; Inhibitory Concentration 50; Plant Extracts; Quinones