Albiflorin, a Monoterpene Glycoside, Protects Myoblasts against Hydrogen Peroxide-Induced Apoptosis by Activating the Nrf2/HO-1 Axis.

Abstract

Albiflorin, a key active compound in the roots of Paeonia lactiflora Pall, is known to have multiple health benefits. Although albiflorin has been shown to exert its major pharmacological effects via its antioxidant activity, its efficacy in the muscles has not been evaluated. In this study, we examined the protective activity of albiflorin against oxidative injury in C2C12 murine myoblasts. C2C12 cells were pretreated with nontoxic concentrations of albiflorin and exposed to hydrogen peroxide (H₂O₂) to mimic oxidative stress. Albiflorin pretreatment inhibited H₂O₂-mediated decrease in cell viability and extracellular release of lactate dehydrogenase, and reduced comet tail formation, 8-hydroxy-2'-deoxyguanosine production, and phosphorylated form of histone 2AX expression, which are representative biomarkers of DNA damage. Albiflorin also blocked H₂O₂-induced apoptosis by inhibiting the activation of caspase-3, which is associated with the maintenance of mitochondrial membrane stability by decreasing the Bax/Bcl-2 expression ratio. Additionally, albiflorin markedly suppressed H₂O₂-induced accumulation of reactive oxygen species (ROS) and decreased glutathione levels, while increasing the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activating heme oxygenase-1 (HO-1) in the presence of H₂O₂. However, artificial inhibition of HO-1 activity using zinc protoporphyrin (ZnPP) markedly abrogated the protective effects of albiflorin against ROS production and mitochondrial damage in H₂O₂-treated cells. ZnPP significantly reversed the protective effects of albiflorin against H₂O₂-induced apoptosis and decreased cell viability. Taken together, these findings suggest that albiflorin protects myoblasts from oxidative stress-induced DNA damage and apoptosis by activating Nrf2/HO-1 signaling, thus highlighting its potential in the management of myofunctional homeostasis.