Hyperoside Promotes Mitochondrial Autophagy Through the miR-361-5p/PI3K/Akt/mTOR Signaling Pathway, Thereby Improving UVB-Induced Photoaging

Ultraviolet radiation B (UVB) radiation can induce oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, impaired barrier function, and an increased risk of cancer. Addressing or preventing photoaging may provide a promising therapeutic avenue for these conditions. Hyperoside (HY), a compound abundantly found in medicinal plants including <i>Hypericum perforatum</i> and <i>Crataegus</i>, has been reported to have various pharmacological activities such as antioxidant, anti-inflammatory, cytoprotective, and antitumor effects; however, there are currently no studies systematically exploring the potential and mechanisms of HY in alleviating skin damage caused by ultraviolet (UV) rays. We investigated the inhibitory effects of HY on oxidative stress responses, reducing keratinocyte aging. HY can also exert these effects by mediating the PI3K/AKT/mTOR signaling pathway through miR-361-5p, maintaining mitochondrial dynamic stability, alleviating mitochondrial dysfunction, and enhancing mitophagy. Additionally, in vivo, HY was able to significantly improve skin wrinkles in mice while reducing changes in thickness and aging of the epidermis and dermis.