Licochalcone D Alleviates Radiation-Induced Intestinal Injury via SIRT3-Dependent Mitophagy: A Natural Phytochemical Strategy for Radioprotection

Oxidative stress, a key mechanism in radiation-induced intestinal injury (RIII), is triggered by ionizing radiation. Licochalcone D (LCD), a bioactive compound derived from licorice, exhibits potent antioxidant properties, yet its role and mechanism in RIII remain unclear. In this study, in vitro experiments revealed that the pretreatment of intestinal epithelial cells with LCD significantly enhanced cell viability, reduced radiation-induced DNA breaks, and suppressed reactive oxygen species (ROS) accumulation. In vivo, LCD administration mitigated radiation-induced body weight loss, preserved intestinal crypt integrity, and attenuated villous damage in irradiated mice. Mechanistically, LCD stabilizes SIRT3 protein to activate mitophagy, thereby eliminating radiation-generated ROS and subsequently alleviating DNA damage and preventing cell apoptosis. These findings broaden the potential applications of LCD in protecting against RIII and establish the SIRT3-mitophagy axis as a novel pharmacological target for preventing radiation-induced intestinal damage.