Identification of Beta-Sitosterol and Stigmasterol as Possible Inhibitors of 5 Alpha-Reductase 1: An In-Silico Study

Abstract

: Dihydrotestosterone (DHT), the most critical pathogenic androgen in hair loss, is identified as an etiologic factor of androgenetic alopecia (AGA). The AGA is a genetically common disorder among men and is characterized by the progressive conversion of hair follicles into small vellus hair. Steroid 5 alpha-reductase type 1 (5AR1) is a crucial target responsible for this gradual replacement. The 5AR1 function is determined by converting testosterone to DHT. The inhibitors of 5AR1 play their role by blocking the DHT production pathway. This study focused on the potent inhibitors of the 5AR1 enzyme to suggest effective synthetic drugs for restoring hair loss with fewer side effects. The three-dimensional structure of 5AR1 was created using homology modeling methods. Then, the inhibitory effects of some significant compounds from natural sources were examined on the 5AR1 protein using molecular docking approaches. The obtained results suggest that two natural compounds isolated from Serenoa repens, including beta-sitosterol and stigmasterol, could inhibit the regular activity of 5AR1 and can be recommended as safe and novel AGA medicines for hair restoration.