Cryptotanshinone Attenuates Ischemia/Reperfusion-induced Apoptosis in Myocardium by Upregulating MAPK3

Chinese people have used the root of Salvia miltiorrhiza Bunge (called "Danshen" in Chinese) for centuries as an anticancer agent, anti-inflammatory agent, antioxidant, and cardiovascular disease drug. In addition, Danshen is considered to be a drug that can improve ischemia/reperfusion (I/R)-induced myocardium injury in traditional Chinese medicine. However, Danshen is a mixture that includes various bioactive substances. In this study, we aimed to identify the protective component and mechanism of Danshen on myocardium through network pharmacology and molecular simulation methods. First, cryptotanshinone (CTS) was identified as a potential active compound from Danshen that was associated with apoptosis by a network pharmacology approach. Subsequently, biological experiments validated that CTS inhibited ischemia/reperfusion-induced cardiomyocyte apoptosis in vivo and in vitro. Molecular docking techniques were used to screen key target information. Based on the simulative results, MAPKs were verified as well-connected molecules of CTS. Western blotting assays also demonstrated that CTS could enhance MAPK expression. Furthermore, we demonstrated that inhibition of the MAPK pathway reversed the CTS-mediated effect on cardiomyocyte apoptosis. Altogether, our work screened out CTS from Danshen and demonstrated that it protected cardiomyocytes from apoptosis.