Isochlorogenic acid C protects mouse embryonic fibroblast cells from oxidative damage via restoring SIRT3-SOD2 activity

Isochlorogenic acid C (ICAC) has been used for the production of scented tea, medicinal tea, and soft drinks. The antiinflammatory, antibacterial, and antiviral properties of ICAC were demonstrated previously. However, it is unknown how ICAC regulates oxidative stress. In the current study, we evaluate the antioxidative potential of ICAC and its effects on the activation of the antioxidant system in mouse embryonic fibroblast NIH/3T3 cells. Our results showed that ICAC protected cells from H 2 O 2 -induced toxicity through protecting cell viability and cytotoxicity. H 2 O 2 -increased cellular reactive oxygen species (ROS), mitochondrial membrance potential (MMP) loss, and mitochondrial calcium were recovered by ICAC treatment. Moreover, cleaved caspase 3, SOD2, and SIRT3 were also regulated by ICAC treatment. Mechanistically, it was found that MAPK pathway is the key regulator in the insight of ICAC treatment. All intracellular changes were abrogated by the application of SIRT inhibitors, JNK inhibitor, and Erk inhibitor, but not by p38 inhibitor. Interestingly, the application of NAC revealed that the behavior of ICAC was similar to NAC regarding antioxidant potential. Conclusively, ICAC was found to be a good candidate for protecting fibroblast cells from apoptosis via reducing oxidative stress and activation of the antioxidant system. Our findings are the first to evaluate the antioxidative characteristics of ICAC and provide the novel insights when assessing the therapeutic roles of antioxidants in future cancer treatment. • Isochlorogenic acid C (ICAC) protects H 2 O 2 -induced cytotoxicity in fibroblast. • SIRT3-SOD2 axis contributes to the protective effects of ICAC on apoptosis. • ICAC regulated cell viability and cytotoxicity partially through MAPK signaling pathway.