Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway

Abstract

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1β (IL-1β) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-β and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.

Paeoniflorin Protects H9c2 Cardiomyocytes against Hypoxia/Reoxygenation Induced Injury via Regulating the AMPK/Nrf2 Signaling Pathway

“…A previous study reported that Galanthamine improves myocardial I/R induced cardiac dysfunction by activating the AMPK/Nrf2 pathway in rats [ 29 ]. Galanthamine improves myocardial I/R-induced cardiac dysfunction by activating AMPK/Nrf2 pathway in rats [ 28 ]. Galanthamine improves myocardial I/R-induced cardiac dysfunction by activating the AMPK/Nrf2 pathway in rats [ 30 ].…”

“…Adenosine monophosphate-activated protein kinase (AMPK), a silk/threonate albuminase composed of three peptide chains, is an important regulator of human energy metabolism and is closely related to promoting catabolism, inhibiting anabolism, improving endothelial function, alleviating inflammatory response, and inhibiting oxygen-reduction reaction [26,27]. It has been shown in previous studies that AMPK can activate Nrf2 through phosphorylation and generate downstream antioxidant genes such as HO-1 and NQO1 to play an antioxidative stress role [28]. Here, we found that PF induced the A previous study reported that Galanthamine improves myocardial I/R induced cardiac dysfunction by activating the AMPK/Nrf2 pathway in rats [29].…”

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

“…The cardioprotective effect of schisandrin B was also shownon H9c2 cardiomyocytes (rat embryonic cardiomyoblasts) in myocardial ischemia-reperfusion injury (MIRI) model through attenuation of the oxidative stress and inflammatory response via the AMPK/Nrf2 signaling pathway. Mechanistically, schisandrin B pretreatment reversed hypoxia/reoxygenation (H/R)-induced iROS generation, higher MDA content, upregulation of Keap1 and decreased enzymatic activities of SOD and GPx but induced the downregulation of pro-inflammatory cytokines (IL-1β, TNF-α and IL-8) and the upregulation of the anti-inflammatory cytokine IL-10 [ 50 , 51 ]. In another study, schisandrin B effectively protected the heart from injury caused by a doxorubicin analog pirarubicin by exerting strong antioxidant capacity [ 137 ].…”

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

“…The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Zhao et al suggested that Schisandrin B attenuates hypoxia/reoxygenation injury by activating the AMPK/Nrf2 signaling pathway [ 54 ]. Thus, Schisandrin B induced AMPK/Nrf2 signaling pathway to suppress NLRP3 inflammasome in model of colitis by the inhibition of ROS-induced mitochondrial damage.…”