Cardioprotective effects of Schisantherin A against isoproterenol-induced acute myocardial infarction through amelioration of oxidative stress and inflammation via modulation of PI3K-AKT/Nrf2/ARE and TLR4/MAPK/NF-κB pathways in rats.

BACKGROUND AND AIMS: The scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats. METHODS: Rats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20. RESULTS: SCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1ß) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats. CONCLUSION: In conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats.

Dioscin attenuates lipopolysaccharide-induced inflammatory myocardial injury through oxidative stress-related pathway.

BACKGROUND: Lipopolysaccharide (LPS) is one of the main causes of myocardial injury. Dioscin has a protective effect on myocardial injury induced by LPS; however, the biological function and mechanism remain unclear. The purpose of this study was to investigate the effect of dioscin on myocardial injury induced by LPS. METHODS: The myocardial injury model was constructed through LPS treatment of primary rat cardiomyocytes. Cardiomyocytes were treated with different concentrations of dioscin (50, 100, and 200 ng/mL). MTT was used to detect the activity of cardiomyocytes; flow cytometry and TUNEL assay were used to detect apoptosis; and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). The release of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) was detected according to the kit instructions. The levels of apoptosis-related proteins (Bax, caspase-3, and Bcl 2) and the Nrf2-Keap1 pathway proteins were detected by western blot. RESULTS: Dioscin significantly reduced LPS-induced cardiomyocyte injury in neonatal rats in a concentration- and time-dependent manner. Dioscin also significantly inhibited cardiomyocyte inflammation and apoptosis induced by LPS. With the increase of dioscin concentration, reactive oxygen species (ROS) and MDA were downregulated, and SOD and GSH were upregulated. Moreover, dioscin inhibited LPS-induced myocardial injury by inhibiting the Nrf2-Keap1 pathway. CONCLUSIONS: Our study suggests that dioscin attenuates LPS-induced myocardial injury through oxidative stress-related pathways.