Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays

Abstract

Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd.

An appraisal of laboratory models of androgenetic alopecia: A systematic review

“…Twenty‐four studies investigated gene expression profiling 18–28 and markers for AGA 29–41 . Fourteen studies focused on the action of 5‐alpha reductase (5AR), which converts the androgen (testosterone) into dihydrotestosterone (DHT) and the inhibition of this enzyme 42–55 using enzymatic, radiochemical and cell proliferation assays. Thirteen studies used the same techniques to investigate the role of other enzymes in the mediation of AGA 4 ,.…”

“…Therefore, some studies used DPCs 43 ,. 45 , 48 , 53 Scalp DPCs are specialized mesenchymal cells of tissues affected by AGA that exist in the dermal papilla located at the basal layer of hair follicles. These cells play a pivotal role in the hair cycle.…”

“…4,6,10,43,[56][57][58][59][60][61][62][63][64][65] To find alternative treatments for AGA, four studies investigated the effect of plant extracts and phytocompounds on the inhibition of 5AR type 2 using the dermal papilla cells (DPCs) proliferation assay. 43,45,48,53 Only three studies investigated efficient drug delivery methods, such as nanotechnology. [66][67][68] In contrast, 27 articles used mice/mice xenografts, rats and monkeys as in vivo models to study the efficacy of Finasteride, Minoxidil and plant extracts/compounds in the treatment of AGA.…”

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Twenty-four studies investigated gene expression profiling [18][19][20][21][22][23][24][25][26][27][28] and markers for AGA. [29][30][31][32][33][34][35][36][37][38][39][40][41] Fourteen studies focused on the action of 5-alpha reductase (5AR), which converts the androgen (testosterone) into dihydrotestosterone (DHT) and the inhibition of this enzyme [42][43][44][45][46][47][48][49][50][51][52][53]…”

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

“…In addition, Cabeza et al reported the effect of βsitosterol to inhibit 5AR1 in the hamster prostate (38). They The aforementioned study proved that stigmasterol and β-sitosterol targeting 5AR and inflammatory mediators might represent a rational approach in treating AGA and BPH (40). Currently, available drugs for AGA are finasteride and dutasteride, which are synthetic.…”