The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

Abstract

GRS is a drug combination of three components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula Sheng MaiSan, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study illuminates its underlying mechanisms against myocardial ischemic diseases based on the combined methods of bioinformatic prediction and experimental verification. A protein database was established through constructing the drug-protein network. And the target-pathway interaction network clustered the potential signaling pathways and targets of GRS in treatment of myocardial ischemic diseases. Several target proteins, such as NFKB1, STAT3 and MAPK14, were identified as the candidate key proteins, and MAPKs and JAK-STAT signaling pathway were suggested as the most related pathways, which were in accordance with the gene ontology analysis. Then, the predictive results were further validated and we found that GRS treatment alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury via suppression of MDA levels and ROS generation, and potential mechanisms might related to the suppression of activation of MAPKs and JAK2-STAT3 signaling pathways. Conclusively, our results offer the evidence that GRS attenuates myocardial ischemia injury via regulating oxidative stress and MAPKs and JAK2-STAT3 signaling pathways, which supplied some new insights for its prevention and treatment of myocardial ischemia diseases.

Dexmedetomidine Pretreatment Protects Against Myocardial Ischemia/Reperfusion Injury by Activating STAT3 Signaling

“…Moreover, some studies found that STAT3 phosphorylation was promoted in a cardiomyocyte H/R model. 37 However, in apparent contradiction to the above findings, our in vitro results and other studies 36 showed that cardiomyocyte H/R challenge inhibited the phosphorylation of STAT3. The disparities between these findings could be associated with different cell lines, durations of H/R, and culture conditions.…”

Schisandrol A Attenuates Myocardial Ischemia/Reperfusion‐Induced Myocardial Apoptosis through Upregulation of 14‐3‐3θ

“…The amounts of proteins A/B, as indicated in the SDS-PAGE, markedly decreased following the serial affinity chromatography, suggesting that the reduced proteins might be the specific SA-binding proteins. Based on the previous network pharmacology and experimental studies [ 21 , 22 ], we further confirmed that 14-3-3 θ protein might be the binding target protein of SA, according to the results of western blot. Additionally, molecular docking was applied to predict the binding modes of 14-3-3 θ and SA.…”

“…On the basis of the obtained results that SA protected cardiomyocytes against apoptosis in vivo and in vitro, further experiments to identify potential target of SA were conducted. The serial affinity chromatography method was carried out to confirm the possible target of SA [20][21][22]. Furthermore, molecular docking and MST method were performed for further analysis.…”