Handelin Attenuates Ultraviolet-Induced Skin Photoaging and Associated Oxidative Stress and Extracellular Matrix Damage in Mice

Chronic ultraviolet (UV) exposure promotes skin photoaging through oxidative stress, inflammation, autophagy-related alterations, and extracellular matrix (ECM) damage. This study evaluated the protective effects of Handelin in a chronic UV-induced mouse photoaging model. Forty male Kunming mice were assigned to Control, UV, UV + Vehicle, and UV + Handelin groups (n = 10/group). Except for the Control group, mice received combined UVA/UVB irradiation for 8 weeks, with Vehicle or Handelin administered intradermally before each exposure. Skin photoaging was assessed by macroscopic scoring, histology, ELISA, immunohistochemistry, and immunofluorescence. Compared with the UV + Vehicle group, Handelin attenuated skin roughness, wrinkle formation, epidermal thickening, and dermal collagen disorganization. Handelin also reduced the ROS-related ELISA signal and the levels of malondialdehyde, interleukin-6, tumor necrosis factor-α, and MMP-3; decreased p-p38 MAPK, p-mTOR, and MMP-1 immunoreactivity; and increased superoxide dismutase protein levels, Beclin-1 and TIMP-1 immunoreactivity, LC3B fluorescence intensity, and type I collagen immunoreactivity. These findings indicate that intradermal Handelin attenuates chronic UV-induced skin photoaging and ECM damage, accompanied by improvements in oxidative stress-related indices and inflammatory markers, changes in mTOR- and autophagy-related markers, and amelioration of MMP/TIMP imbalance.