salvianolic-acid-B and Myocardial-Ischemia

Salvianolic acid B (SalB) has been extensively investigated in our laboratory for myocardial ischemia (MI) disease. This study mainly aimed to illustrate the relationship between SIRT1 and the therapeutic effect of SalB on MI in rats and hypoxia damage in H9c2 cells. Furthermore, whether the antagonism of NLRP3 by SalB in the injuries mentioned above is related to SIRT1-AMPK-PGC-1α pathway-mediated mitochondrial biogenesis was further investigated. In vivo, 24 h after MI surgery, we found that SalB effectively reduced ST-segment elevation, myocardial infarct size enlargement, cardiac injury markers, myocardial structural abnormalities, and myocardial apoptotic cells in MI injury rats. In vitro, after 4 h of hypoxia exposure, SalB alleviated cell injury, inhibited the production of ROS and IL-1β, and prevented the loss of mitochondrial membrane potential (MMP). Besides, SalB downregulated the critical components of the NLRP3 inflammasome and upregulated the SIRT1-AMPK-PGC-1α signaling pathway-related molecules in myocardial tissues and H9c2 cells. However, all the above protective effects of SalB on MI could be offset by EX527. Taken together, our findings indicated that SalB could attenuate MI injury by targeting NLRP3, which is at least partially dependent on the SIRT1/AMPK/PGC-1α signaling pathway.

Topics: AMP-Activated Protein Kinases; Animals; Benzofurans; Cardiomegaly; Hypoxia; Inflammasomes; Myocardial Ischemia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1

Ischemic heart disease is a major cause of mortality and disability worldwide. Salvianolic acid B (Sal B) is one of the main water‑soluble components of Salvia miltiorrhiza Bge. Numerous studies have demonstrated that Sal B could exert significant anti‑inflammatory and cardiovascular protective effects; however, the underlying mechanisms remain unclear. To elucidate the association between myocardial ischemia and inflammation, and to develop effective protective drugs, a rat model of myocardial ischemia was induced using isoproterenol (ISO) and an inflammation model in H9C2 cells was induced with lipopolysaccharide + adenosine triphosphate. Both of these models were treated with different concentrations of Sal B (5, 10 and 15 mg/kg in vivo; 1, 5 and 25 µM in vitro). In vivo, the serum levels of creatine kinase isoenzyme MB, glutamic oxaloacetic transaminase and IL‑1β, the cardiac function and the mRNA expression levels of NLR family pyrin domain‑containing 3 (NLRP3) inflammasome components were evaluated using ELISAs, an electrocardiogram, hematoxylin and eosin staining and reverse transcription‑quantitative PCR, respectively. The results demonstrated that treatment with Sal B markedly alleviated the acute myocardial ischemic injury induced by hypodermic injection of ISO in rats. In vitro, the results of reactive oxygen species (ROS) detection, JC‑1 staining, western blotting and TUNEL assays showed that Sal B treatment significantly inhibited intracellular ROS production, increased the mitochondrial membrane potential, regulated the expression of mitophagy‑related proteins, inhibited the activation of the NLRP3 inflammasome and inhibited apoptosis in H9C2 cells. In conclusion, these findings indicated that Sal B exerted protective effects against myocardial ischemic injury by promoting mitophagy and maintaining mitochondrial function.

Topics: Animals; Apoptosis; Benzofurans; Cell Line; China; Disease Models, Animal; Inflammasomes; Inflammation; Ischemia; Lipopolysaccharides; Male; Mitophagy; Myocardial Ischemia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 4

Salvianolic acid B is one of the main water-soluble components of Salvia miltiorrhiza Bge. Many reports have shown that it has significant anti-myocardial ischemia effect. However, the underlying mechanism remains unclear. Our present study demonstrated that Sal B could alleviate myocardial ischemic injury by inhibiting the priming phase of NLRP3 inflammasome. In vivo, serum c-troponin I (cTn), lactate dehydrogenase (LDH) levels, the cardiac function and infract size were examined. We found that Sal B could notably reduce the myocardial ischemic injury caused by ligation of the left anterior descending coronary artery. In vitro, Sal B down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated H9C2 cells. Furthermore, Sal B reduced the expression levels of IL-1β and NLRP3 inflammasome in a dose-dependent manner. In short, our study provided evidence that Sal B could attenuate myocardial ischemic injury via inhibition of TLR4/NF-κB/NLRP3 signaling pathway. And in an upstream level, MD-2 may be the potential target.

Topics: Animals; Benzofurans; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Lipopolysaccharides; Lymphocyte Antigen 96; Male; Models, Molecular; Myocardial Ischemia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Signal Transduction; Toll-Like Receptor 4

To achieve the combination therapy of acute myocardial ischemia, arginyl-glycyl-aspartic acid (RGD) conjugated lipid was synthesized and RGD modified, salvianolic acid B (Sal B) and panax notoginsenoside (PNS) co-loaded lipid-polymer hybrid nanoparticles (RGD-S/P-LPNs) was fabricated an evaluated.. The LPNs are generally spherical in shape with uniform size distribution, have sizes of 100-200nm and zeta potentials range from -30.7∼ -39.8. In vitro release behaviors of drugs loaded LPNs are in a sustained release manner, which does not exhibit obviously cytotoxicity against H9c2 cardiomyocytes. RGD-S/P-LPNs group shows the most significant cardiac distribution and infarct therapy effect in vivo.. The results illustrated that RGD modified dual drugs co-loaded LPNs are stable, sustained release carriers. Cardiac distribution, pharmacokinetics, and infarct therapy effect results suggested that the RGD-S/P-LPNs could improve the in vivo therapeutic efficacy of the double drugs.

Topics: Animals; Benzofurans; Cell Line; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Therapy, Combination; Ginsenosides; Integrin alphaVbeta3; Lipids; Male; Myocardial Ischemia; Nanomedicine; Nanoparticles; Oligopeptides; Panax; Peptides; Phosphatidylethanolamines; Polyethylene Glycols; Polymers; Rats; Rats, Sprague-Dawley

Salvianolic acid A (Sal A), an important constituent of Radix Salviae Miltiorrhizae (RSM), is effective for the treatment of myocardial infarction (MI) and coronary heart disease due to its potential in the improvement of acute myocardial ischemia. However, its content is very low in RSM. So it is obvious to find a rich source of Sal A or to improve its content by conversion of other related components into Sal A modifying reaction conditions. In this research we focused on the conversion of Sal B into Sal A in aqueous solutions of RSM by using different reaction conditions including pH, temperature, pressure and humidity. During the reactions, the contents of Sal A, Sal B and danshensu in the RSM were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LCMS). The results indicated that the conversion of Sal B into Sal A in RSM tissues under the conditions of a high temperature, high pressure and high humidity was efficient and thereby, was readily utilized to prepare rich Sal A materials in practice.

Topics: Benzofurans; Caffeic Acids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hot Temperature; Humidity; Lactates; Mass Spectrometry; Myocardial Ischemia; Phytotherapy; Plant Roots; Pressure; Salvia miltiorrhiza