Jain Ruchy, Monthakantirat Orawan, Tengamnuay Parkpoom, De-Eknamkul Wanchai
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Research Unit of Natural Product Biotechnology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
BMC Complement Altern Med. 2016 Jan 21;16:18. doi: 10.1186/s12906-016-1004-5.
Androgenic alopecia (AGA) is a major type of human scalp hair loss, which is caused by two androgens: testosterone (T) and 5α-dihydrotestosterone (5α-DHT). Both androgens bind to the androgen receptor (AR) and induce androgen-sensitive genes within the human hair dermal papilla cells (HHDPCs), but 5α-DHT exhibits much higher binding affinity and potency than T does in inducing the involved androgen-sensitive genes. Changes in the induction of androgen-sensitive genes during AGA are caused by the over-production of 5α-DHT by the 5α-reductase (5α-R) enzyme; therefore, one possible method to treat AGA is to inhibit this enzymatic reaction.
RT-PCR was used to identify the presence of the 5α-R and AR within HHDPCs. A newly developed AGA-relevant HHDPC-based assay combined with non-radioactive thin layer chromatography (TLC) detection was used for screening crude plant extracts for the identification of new 5α-R inhibitors.
HHDPCs expressed both 5α-R type 1 isoform of the enzyme (5α-R1) and AR in all of the passages used in this study. Among the thirty tested extracts, Avicennia marina (AM) displayed the highest inhibitory activity at the final concentration of 10 μg/ml, as the production of 5α-DHT decreased by 52% (IC50 = 9.21 ± 0.38 μg/ml).
Avicennia marina (AM) was identified as a potential candidate for the treatment of AGA based on its 5α-R1-inhibitory activity.
雄激素性脱发(AGA)是人类头皮脱发的主要类型,由两种雄激素引起:睾酮(T)和5α-二氢睾酮(5α-DHT)。这两种雄激素均与雄激素受体(AR)结合,并在人毛发真皮乳头细胞(HHDPCs)内诱导雄激素敏感基因,但在诱导相关雄激素敏感基因方面,5α-DHT表现出比T更高的结合亲和力和效力。AGA期间雄激素敏感基因诱导的变化是由5α-还原酶(5α-R)过度产生5α-DHT所致;因此,一种治疗AGA的可能方法是抑制这种酶促反应。
采用逆转录聚合酶链反应(RT-PCR)鉴定HHDPCs中5α-R和AR的存在。一种新开发的基于AGA相关HHDPCs的检测方法结合非放射性薄层色谱(TLC)检测,用于筛选粗植物提取物以鉴定新的5α-R抑制剂。
在本研究使用的所有传代中,HHDPCs均表达该酶的5α-R 1型同工型(5α-R1)和AR。在30种受试提取物中,白骨壤(AM)在终浓度为10μg/ml时表现出最高的抑制活性,因为5α-DHT的产生减少了52%(IC50 = 9.21±0.38μg/ml)。
基于白骨壤(AM)的5α-R1抑制活性,其被鉴定为治疗AGA的潜在候选物。