Evaluation of Efficacy of Water-Soluble Fraction of Rhus semialata Gall Extract and Penta-O-Galloyl-β-D-Glucose on Mitigation of Hair Loss: An In Vitro and Randomized Double-Blind Placebo-Controlled Clinical Study

Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of <i>Rhus semialata</i> gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose (PGG), through both in vitro and clinical studies. WRGE was obtained using a standardized extraction process, and PGG was identified via HPLC-DAD and HRESIMS/MS techniques. Human dermal papilla cells (HDPCs) are specialized fibroblasts that can regulate the hair growth cycle and hair follicle growth. HDPCs are widely used in research focused on anti-hair loss. In this study, the anti-hair loss effects of WRGE and PGG on HDPCs were confirmed. WRGE and PGG enhance cell proliferation in HDPCs. These results are associated with the activation of the Wnt/β-catenin signaling pathway and the upregulation of hair growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor (FGF). Furthermore, WRGE and PGG significantly inhibited dihydrotestosterone (DHT)-mediated DKK-1 secretion and H₂O₂-medicated cytotoxicity. Clinical trials further validated these results, demonstrating significant improvements in hair density and visual hair appearance scores in participants treated with WRGE compared to a placebo group. These results collectively suggest that WRGE and PGG may serve as promising natural agents for the prevention and treatment of hair loss by targeting multiple biological pathways, including the regulation of hair growth factors, oxidative stress, and hormonal imbalances.