Camellia nitidissima Flower Extract Alleviates Dermal Papilla Cell Dysfunction by Regulating 11β-HSD1 and the TGF-β2/Smad and Wnt/β-Catenin Pathways.

Psychological stress activates the local hypothalamic-pituitary-adrenal (HPA)-like axis in hair follicles, leading to cortisol overproduction and dysfunction of dermal papilla cells (DPCs). However, effective natural ingredients targeting this mechanism remain scarce. To investigate whether Camellia nitidissima flower extract (CNF) alleviates stress-induced DPC dysfunction by inhibiting 11β-Hydroxysteroid dehydrogenase type 1(11β-HSD1) and modulating the downstream signaling pathways. The phytochemical composition of CNF was characterized using HPLC-DAD. An in vitro stress-induced injury model was established in human DPCs using corticotropin-releasing factor (CRF). Cortisol levels as well as the secretion levels of hair growth factors were measured by ELISA. The expression of 11β-HSD1 was assessed via immunofluorescence. Oxidative stress was evaluated by reactive oxygen species (ROS) fluorescence and superoxide dismutase (SOD) activity. Apoptosis was analyzed by flow cytometry (Annexin V-FITC/PI). Protein expression of the TGF-β2/Smad pathway and mitochondrial apoptosis-related proteins was detected by western blotting. Cell proliferation was assessed by Ki67 immunofluorescence and cell cycle analysis. The mRNA expression of Wnt/β-catenin pathway components was quantified by Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Ten bioactive constituents, predominantly the polyphenolic compounds rutin and quercetin-7-O-β-D-glucoside, were identified in CNF. Mechanistically, CNF disrupted the local "stress-cortisol" amplification loop by first reducing CRF-induced cortisol secretion and downregulating 11β-HSD1 expression in DPCs. This upstream intervention subsequently attenuated oxidative stress and inhibited CRF-induced apoptosis via suppression of the TGF-β2/Smad2/3 pathway, while concurrently restoring proliferative capacity through reactivation of the Wnt/β-catenin signaling axis. These coordinated molecular events ultimately reinstated the secretion of key hair growth factors, including Alkaline phosphatase (ALP), Vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF), Epidermal growth factor (EGF), and insulin-like growth factor 1 (IGF-1), thereby mitigating DPC dysfunction.