Naringin Ameliorates IL-6 Mediated mitochondrial dysfunction and skeletal muscle degeneratio via AMPK/Nrf-2 pathway

Abstract

Abstract Ethnopharmacological relevance: Paraspinal muscle degeneration often arises as a hazardous consequence of intervertebral disc degeneration (IVDD). This degeneration correlates with oxidative stress and mitochondrial dysfunction. This study investigated the therapeutic potential of naringin in managing paraspinal muscle degeneration associated with disc degeneration. Materials and methods: C2C12 cells were stimulated with IL-6 to establish an in vitro model of skeletal muscle degeneration for assessing the protective impact of naringin on skeletal muscle. The most effective concentration of naringin in C2C12 cells was identified through a CCK8 assay. The antioxidant prowess of naringin was evaluated via biochemical methods and Elisa. The influences of naringin and IL-6 on apoptosis, mitochondrial function, and associated signaling pathways were examined using cytometry, ROS detection, western blot, and transmission electron microscopy. Results: Our findings demonstrated a significant reduction in discogenic paraspinal degeneration with naringin therapy. Naringin glycosides notably enhanced the expression of key proteins involved in both muscle anabolism and catabolism, including MAFbx, MuRF1, MyoD, and MyoG.Moreover, naringin contributed to maintaining redox homeostasis by augmenting antioxidant activity and preventing excessive ROS peroxide accumulation. To impede paraspinal muscle degeneration, naringin upregulated MyoD and MyoG expression while downregulating MAFbx and MuRF1 through the activation of AMPK/Nrf-2 signaling pathway. Conclusion: These findings underscore naringin's robust therapeutic potential in enhancing mitochondrial activity, regulating oxidative stress, and halting paraspinal muscle degeneration.