Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Abstract

In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and γH2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keap1) expression. Notably, these events were eliminated by transient transfection with Nrf2‑specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal‑regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO‑1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2-induced oxidative cytotoxicity.

DADLE improves hepatic ischemia/reperfusion injury in mice via activation of the Nrf2/HO-1 pathway

“…Prevention of I/R injury in organs has garnered much attention in recent years. Numerous studies have reported that some compounds can induce upregulation of the Nrf2/HO-1 pathway to exert protective effects on various I/R models (40)(41)(42)(43). The present study demonstrated that targeting the Nrf2/HO-1 pathway may provide a novel strategy for preventing hepatic I/R injury.…”

Melatonin protects H9c2 cells against ischemia/reperfusion‑induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway

“…HO-1 is a target gene of Nrf2, which is involved in regulating cellular ROS production and scavenging (35,36). Activation of Nrf2-HO-1 signaling may alleviate myocardial I/R injury (37). In the present study, SIR treatment was observed to enhance the expression of Nrf2 in the nucleus and the whole cell, which may suggest increased nuclear translocation.…”

Impact of Antioxidant Natural Compounds on the Thyroid Gland and Implication of the Keap1/Nrf2 Signaling Pathway

“…Morin exerts cytoprotective and genoprotective effects against oxidative stress. Morin treatment prior to H 2 O 2 exposure significantly prevented the generation of ROS, increased cell viability and prevented DNA damage by up-regulating Nrf2-dependent HO-1 expression through extracellular signal-regulated kinases (ERK) in C2C12 myoblasts [133]. In the case of myricetin, production of pro-inflammatory mediators through the suppression of signal transducer and activator of transcription 1 (STAT1) and Nuclear factor kappa-lightchain-enhancer of B cells (NF-kB) activation was inhibited by induction of Nrf2-mediated HO-1 expression in LPS-stimulated macrophages [134].…”