Combating Skin Photoaging with Natural Products: Molecular Mechanisms, Nanodelivery Strategies, and Clinical Translation

Skin aging is a complex biological process, and extrinsic photoaging driven by ultraviolet (UV) radiation accounts for approximately 80% of visible facial aging signs. Natural bioactive compounds have attracted increasing interest in anti-photoaging research because of their multi-target regulatory effects and diverse biological activities. This narrative review elucidates the molecular pathogenesis of skin photoaging, highlights the therapeutic potential of natural products, introduces advanced nanodelivery systems, and discusses clinical translation. The molecular pathogenesis of photoaging involves an interconnected regulatory network linking oxidative stress, chronic inflammation, and extracellular matrix (ECM) dysregulation, in which UV-induced reactive oxygen species (ROS) initiate oxidative damage, activate multiple inflammatory signaling pathways, and further cause ECM dysregulation; these processes interact through reciprocal mechanisms and self-amplifying feedback loops, ultimately leading to skin sagging and wrinkle formation. The core mechanisms of natural products against photoaging cover direct ROS scavenging and activation of Nrf2/ARE pathway to enhance antioxidant capacity, inhibition of NF-κB-mediated inflammation and suppression of senescence-associated secretory phenotype (SASP) to alleviate cutaneous inflammaging, as well as dual regulation through the MAPK/AP-1 and TGF-β/Smad pathways to preserve ECM structure. To facilitate their application, a range of advanced nanodelivery systems, including liposomes, flexible vesicles, nanoemulsions, lipid nanoparticles, polymeric micelles, biopolymer-based nanoparticles, and smart nanotechnologies, are explored to enhance their anti-photoaging efficacy. Furthermore, clinical evidence, safety assessment, and translational challenges associated with natural anti-photoaging compounds and their nanoformulations are discussed. Collectively, natural products combined with advanced nanodelivery systems offer promising strategies for preventing skin photoaging, although further clinical validation is needed.