This study establishes the effectiveness of naturally occurring 5AR inhibitors against AGA for the first time, and justifies the expansion to larger trials.
Chronic inflammation of the hair follicle (HF) is considered a contributing factor in the pathogenesis of androgenetic alopecia (AGA). Previously, we clinically tested liposterolic extract of Serenoa repens (LSESr) and its glycoside, β-sitosterol, in subjects with AGA and showed a highly positive response to treatment. In this study, we sought to determine whether blockade of inflammation using a composition containing LSESr as well as two anti-inflammatory agents (carnitine and thioctic acid) could alter the expression of molecular markers of inflammation in a well-established in vitro system. Using a well-validated assay representative of HF keratinocytes, specifically, stimulation of cultured human keratinocyte cells in vitro, we measured changes in gene expression of a spectrum of well-known inflammatory markers. Lipopolysaccharide (LPS) provided an inflammatory stimulus. In particular, we found that the composition effectively suppressed LPS-activated gene expression of chemokines, including CCL17, CXCL6 and LTB(4) associated with pathways involved in inflammation and apoptosis. Our data support the hypothesis that the test compound exhibits anti-inflammatory characteristics in a well-established in vitro assay representing HF keratinocyte gene expression. These findings suggest that 5-alpha reductase inhibitors combined with blockade of inflammatory processes could represent a novel two-pronged approach in the treatment of AGA with improved efficacy over current modalities.
This study establishes the effectiveness of naturally occurring 5AR inhibitors against AGA for the first time, and justifies the expansion to larger trials.
Drug-based monotherapy provides limited clinical benefits in polygenic disorders, such as androgenetic alopecia. Possible benefits must be measured against non-trivial risks of negative side effects. Several well-controlled, peer-reviewed, basic science studies have demonstrated novel mechanisms of action and potential utility for natural-based phytochemicals in the treatment of androgen-mediated disorders, including androgenetic alopecia. Yet, due to phytochemical instability, volatility, and incompatibility, the bridge from in vitro potential to clinical efficacy remains largely unmet. Recent advances in nanomaterial manipulation provide enhanced platforms, such as cyclodextrins, in which these phytochemicals may be enveloped and delivered without triggering the loss of intended function. Unexpected, positive results of an uncontrolled case series for a cyclodextrin-enabled, natural-based formula containing γ linolenic acid, β-Sitosterol, epigallocatechin gallate, and genistein, administered concomitantly via oral and topical form in two androgenetic alopecia-affected, male subjects over the course of 270 days were found. At baseline, significant baldness in the vertex scalp of both subjects was observed. Subsequent 90-day time points demonstrated marked hair thickening. On treatment day 270 (conclusion), scalp hair loss was no longer evident in either patient. Particularly in the setting of a disorders, such as androgenetic alopecia, nano-complexed, botanically-based compositions may offer beneficial adjunctives or alternatives to traditional drug-based/surgical medical treatments.
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