Hesperidin protects C2C12 myoblasts from oxidative damage by reducing ROS-mediated mitochondrial damage and endoplasmic reticulum stress

Abstract

Background

Hesperidin, a flavanone glycoside found primarily in the peel of citrus fruits, has benefits as a natural compound for preventing various diseases, but its inhibitory effect against oxidative injury in muscle cells has not been reported.

Objective

The current study aimed to investigate whether hesperidin can prevent oxidative damage in C2C12 murine myoblasts.

Results

Hesperidin was able to inhibit cytotoxicity while blocking hydrogen peroxide (H₂O₂) H₂O₂-induced DNA damage and apoptosis. Hesperidin also significantly improved the antioxidant capacity of C2C12 cells exposed to H₂O₂ by suppressing cellular reactive oxygen species production and increasing glutathione level. Additionally, H₂O₂-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress were effectively attenuated in the presence of hesperidin. Moreover, hesperidin neutralized H₂O₂-induced calcium ion (Ca²⁺) overload in mitochondria and mitigated the expression of cytosolic Ca²⁺-dependent proteases.

Conclusion

These results imply that hesperidin protects against mitochondrial impairment and Ca²⁺-mediated ER stress by minimizing oxidative stress, thereby suppressing H₂O₂-induced cytotoxicity in C2C12 myoblasts.