Icariside II relieves radiation enteritis by regulating PINK/ Parkin-mediated mitophagy

Radiation enteritis (RE) is one of the major side effects of radiotherapy. So far, there are no effective drugs for preventing the disease process. Icariside II (ICS II) is a highly efficient monomer compound extracted and purified from the classic Chinese medicinal herb Epimedium. It has anti-inflammatory, antioxidant, and immunomodulatory effects. However, the role and mechanism of ICS II on radiation enteritis are not clear. Here, we reveal the role of ICS II in radiation enteritis by using an irradiation-induced rat model and a human colorectal cancer cell (CaCo2). After intragastric administration, HE staining and Tunel staining to observe the histopathological changes in the colon, and TEM to observe the ultrastructure of mitochondria; The antioxidant indexes and mitochondrial function-related markers of colon tissues were determined; DCFH-DA fluorescent probe were used to detect the cellular ROS level, JC-1 staining was used to detect the changes in mitochondrial membrane potential, and Western Blot was used to detect related protein expression. The results showed that ICS II could reduce intestinal injury and attenuate the radiation-induced oxidative stress and inflammatory response. In addition, ICS II could effectively attenuate mitochondrial damage and activate mitochondrial autophagy in rats. Mechanistically, ICS II activates mitochondrial autophagy-related protein expression to rescue radiationinduced damage to mitophagy. We found that by inhibiting mitophagy, the therapeutic effect of ICS II can be eliminated and our data suggest that ICS II may be a new and effective drug candidate for the treatment of radiation enteritis.