Molecular mechanisms of traditional Chinese medicine in skin aging: a narrative review.

Skin aging involves complex endogenous and extrinsic mechanisms, driving oxidative stress, cellular senescence, DNA damage, and extracellular matrix degradation. This narrative review synthesizes preclinical evidence on traditional Chinese medicine (TCM)-derived botanical drugs and formulae targeting these pathways. We identified 19 single-botanical drug and 17 formula studies. The most consistently reported effects include Nrf2/ARE activation, reduced reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) activity, matrix metalloproteinase (MMP) inhibition, and lower senescence markers [p16, p21, and senescence-associated β-galactosidase (SA-β-Gal)]. Additional modulated pathways include MAPK/AP-1, PI3K/Akt/mTOR, TGF-β/Smad, and NAD+/Sirtuin, collectively contributing to reduced inflammation, enhanced antioxidant defense, and preserved dermal collagen. These findings suggest multi-pathway modulation rather than true pharmacological synergy. This system-level approach highlights a shift from monotherapy toward holistic intervention. However, clinical evidence remains extremely limited and consists mainly of small human studies, including trials described as randomized or double-blind but incompletely reported, and single-arm evaluations; no adequately powered, preregistered, high-quality randomized controlled trial (RCT) has yet established clinical efficacy for TCM interventions in skin aging. Therefore, future research should prioritize rigorous RCTs, dose-response designs, and phytochemical standardization.