Abstract
Simple SummaryDihydrotestosterone (DHT), the most potent androgen hormone, is an important aetiologic factor of androgenetic alopecia (AGA), or hair loss. Steroid 5-alpha reductases (SRD5As) increase DHT production in the scalp hair follicles, resulting in hair thinning and hair loss. Even though synthetic SRD5A inhibitors (finasteride and dutasteride) are effective in treating AGA, they cause adverse effects. This has led to an increased interest in alternative treatments from natural sources. The value of Thai rice bran has increased because several of its components may have use in AGA treatment. This study aimed to compare the suppression of the expression of SRD5A genes (type 1–3) exerted by several Thai rice bran extracts and investigate the interactional mechanism of their components towards SRD5A type 2. Tubtim Chumphae rice bran (TRB) had the highest sum of overall bioactive compounds. Among all extracts, the expression of SRD5A genes was suppressed by TRB as well as finasteride. In silico simulation showed that α-tocopherol had the greatest interaction with SRD5A type 2. Our findings identified α-tocopherol as the key bioactive in TRB; it could be developed as an anti-hair loss product.Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydrotestosterone, a potent androgen, which is the aetiologic factor of androgenetic alopecia. This study aimed to compare the SRD5A gene expression suppression activity exerted by Thai rice bran extracts and their components and investigate the interactional mechanism between bioactive compounds and SRD5A2 using molecular dynamics (MD) simulation. Bran of Oryza sativa cv. Tubtim Chumphae (TRB), Yamuechaebia Morchor (YRB), Riceberry (RRB), and Malinil Surin (MRB), all rice milling by-products, was solvent-extracted. The ethanolic extract of TRB had the highest sum of overall bioactive compounds (γ-oryzanol; α-, β-, and γ-tocopherol; phenolics; and flavonoids). Among all extracts, TRB greatly downregulated the expression of SRD5A1, SRD5A2, and SRD5A3; there were no significant differences between TRB and finasteride regarding SRD5A suppression. The linear relationship and principal component analysis supported that the α-tocopherol content was correlated with the SRD5A suppression exerted by TRB. Furthermore, MD simulation demonstrated that α-tocopherol had the highest binding affinity towards SRD5A2 by interacting with residues Phe118 and Trp201. Our findings indicate that α-tocopherol effectively downregulates the expression of SRD5A genes and inhibits SRD5A2 activity, actions that are comparable to standard finasteride. TRB, a source of α-tocopherol, could be developed as an anti-hair loss product.
Highlights
Androgenetic alopecia (AGA), characterised by the progressive replacement of terminal hair into small vellus hair, is generally known as a hereditary androgen-dependent disorder [1]
Tocopherols are the major group of natural antioxidants in rice bran and have a similar chemical structure based on a 6-chromanol amphiphilic ring with one to three methyl groups and a phytyl tail with three chiral centres, resulting in α, β, γ, and δ-tocopherol [26]
Pigmented rice bran contains about 9.67–116.60 mg/kg of α-tocopherol, which is higher than that in non-pigmented rice bran [54]. β-Tocopherol is present at only minor concentrations in rice bran extracts [55], and the pair of β- and γ-tocopherol isomers is not completely separated using reversephase high-performance liquid chromatography (HPLC) [30]
Summary
Androgenetic alopecia (AGA), characterised by the progressive replacement of terminal hair into small vellus hair, is generally known as a hereditary androgen-dependent disorder [1]. SRD5A1, SRD5A2, and SRD5A3 are encoded by separate genes: SRD5A1, SRD5A2, and SRD5A3, respectively While these isozymes share sequence homology and show similar substrate preferences, they vary in biochemical properties, sensitivity to SRD5A inhibitors, physiological functions, and tissue distribution [8]. DHT has a 5-fold higher affinity for the androgen receptor and a 10-fold greater potency for provoking androgen-sensitive genes compared with its precursor [9]. These androgen-sensitive gene products, transforming growth factor beta 1, interleukin 6, and dickkopf 1, have been identified as androgen-inducible negative mediators for AGA development [10]
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