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Anti-Skin Aging Potential of Methoxyflavones from Kaempferia parviflora Against TNF-α-Induced Oxidative Stress and Photoaging in Normal Human Dermal Fibroblasts

Si-young Ahn,Seoyeon Jeong,Bum Soo Lee,Yun Seok Joh,Hamed Hamishehkar,Sullim Lee,Ki Hyun Kim

Published 2025 in Foods

ABSTRACT

Reactive oxygen species (ROS) generated by ultraviolet (UV) radiation accelerate skin aging by activating matrix metalloproteinase-1 (MMP-1) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, antioxidants that can suppress ROS generation and downstream signaling cascades are considered promising anti-aging agents. In this study, five methoxyflavones were isolated from Kaempferia parviflora (black ginger) rhizomes—5,7,3′,4′-tetramethoxyflavone (1), 3,5,7,4′-tetramethoxyflavone (2), 5,7,4′-trimethoxyflavone (3), 3,5,7,3′,4′-pentamethoxyflavone (4), and 5,7-dimethoxyflavone (5)—using LC–MS-guided fractionation and identified via NMR and LC–MS analysis. Their biological activities were evaluated in tumor necrosis factor-α (TNF-α)-stimulated normal human dermal fibroblasts (NHDFs). All methoxyflavones, except compound 3, significantly suppressed TNF-α-induced ROS generation, while compounds 3–5 markedly reduced MMP-1 secretion. Among them, compounds 4 and 5 exerted the strongest protective effects by modulating distinct MAPK pathways: compound 4 selectively inhibited p38 phosphorylation, whereas compound 5 selectively suppressed ERK phosphorylation. Both compounds attenuated ECM degradation and enhanced antioxidant defenses in a concentration-dependent manner. Collectively, these findings highlight the mechanistic significance of methoxyflavones 4 and 5 as dual-acting antioxidant and ECM-protective agents that counteract skin aging through selective regulation of MAPK signaling. Their potential as natural anti-photoaging ingredients warrants further validation in in vivo models and clinical studies for future skincare applications.

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