Natural Product Modulation of Oxidative Stress in the Treatment of Extrinsic Skin Aging: Mechanisms of Action and Future Perspectives

doi:10.1007/s40242-026-6027-y

Abstract

Abstract: Extrinsic skin aging reflects cumulative exposome stressors, dominated by ultraviolet radiation and compounded by pollution and smoking. These inputs converge on oxidative stress, which triggers stress kinases and inflammatory transcriptional programs, elevates matrix metalloproteinases, suppresses collagen-anabolic signaling, and weakens the epidermal barrier. Here, we synthesize natural products that target this cascade and organize them by biological source and chemical scaffold to link structure with mechanisms. We map actions onto two tracks: damage interception by limiting reactive oxygen species (ROS) and stress signaling, including Nrf2-linked defenses and DNA photoprotection, and by restraining activator protein 1 (AP-1), nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs); and repair enhancement via extracellular matrix (ECM) rebuilding and barrier restoration. We appraise evidence from 2D cells to 3D skin, animal UV models, and human studies, highlight dose and formulation pitfalls, and propose combination regimens pairing UV filters with bioactives. Finally, we close with translational priorities in delivery, stability, standardization, photosafety, and endpoint-driven clinical trials for personalized systems-level prevention.

Key words: Skin aging, Photoaging, Natural product, Oxidative stress

ZHANG Xiujun, WANG Jiaxuan, KANG Jingjing, LI Jingqi, LI Junchen, GUO Chenqi, HAO Zhiqiang, LIU Dingbin. Natural Product Modulation of Oxidative Stress in the Treatment of Extrinsic Skin Aging: Mechanisms of Action and Future Perspectives[J]. Chemical Research in Chinese Universities, 2026, 42(2): 571-585.

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