Cardiospermum halicacabum Extract Attenuates UVB-Induced Photoaging in Human Skin Fibroblasts via Inhibition of the PI3K/Akt/mTOR Signaling Pathway

Solar ultraviolet B (UVB) irradiation is a primary environmental driver of skin photoaging, characterized by oxidative stress accumulation and mitochondrial dysfunction. In this study, we investigated the protective efficacy and underlying molecular mechanisms of Cardiospermum halicacabum extract (CHE) against UVB-induced senescence in human skin fibroblasts (HSFs). Phytochemical profiling via LC-MS characterized CHE as a rich source of bioactive flavonoids, organic acids, and glycosides. We demonstrated that pretreatment with CHE significantly ameliorated UVB-triggered cellular senescence, as evidenced by the alleviation of cell cycle arrest and the downregulation of senescence-associated markers p53 and p16. Furthermore, CHE effectively inhibited intracellular ROS generation and restored mitochondrial respiratory function. Transcriptomic analysis, validated by molecular assays, revealed that CHE exerts its protective effects primarily by suppressing the UVB-induced hyperactivation of the PI3K/Akt/mTOR signaling cascade. Collectively, these preliminary in vitro findings highlight CHE as a promising natural protective candidate that mitigates skin photoaging by targeting the PI3K/Akt/mTOR axis to attenuate oxidative stress and restore mitochondrial homeostasis.