Flavonoids in rosacea therapy: multi-target mechanisms from preclinical models to clinical translation

Abstract

Abstract Background Recent years, natural plant components, especially flavonoids, known for their anti-inflammatory, antioxidant, and immunomodulatory properties, show potential in the treatment of rosacea. Objective This review aims to synthesize and critically evaluate the advancements in the therapeutic application of flavonoid compounds for rosacea, encompassing both clinical studies and experimental outcomes from in vitro and in vivo models, thereby providing a reference for future research directions and treatment strategies. Methods A systematic literature search was conducted in Web of Science, PubMed, ScienceDirect, Wiley, and Embase up to 26 September 2024, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a comprehensive set of rosacea- and flavonoid-related keywords. Results In vitro studies indicate that flavonoids modulate the Sirtuin 3 (SIRT3)-Superoxide Dismutase 2 (SOD2)-Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis and suppress inflammatory mediators such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-17 (IL-17). They also regulate Vascular Endothelial Growth Factor (VEGF), Transient Receptor Potential Vanilloid 1 (TRPV1), Kallikrein-related Peptidase 5 (KLK5), and Protease-Activated Receptor 2 (PAR2), contributing to neurogenic inflammation control and skin barrier repair. In vivo models show reduced inflammatory infiltration and angiogenesis. Early clinical studies suggest good safety profiles and potential synergy with standard therapies, though larger Randomized Controlled Trials (RCTs) are needed. Conclusions Flavonoids exert multi-target effects in rosacea via anti-inflammatory and vascular-modulating mechanisms. Future research should prioritize advanced neuroimmune models, enhanced delivery systems, and patient stratification approaches to optimize clinical application.