title: Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κB signaling pathway.
abstract: Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF-κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B-cell lymphoma-2 associated X protein and caspase-3 expressions and increased B-cell lymphoma-2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF-κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats.
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, 121001, PR China.
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Aina
authors.initials: A
authors.lastname: Luan
authors.forename: Meng
authors.initials: M
authors.lastname: Mei
authors.forename: Chonghua
authors.initials: C
authors.lastname: Xu
authors.forename: Suping
authors.initials: S
authors.lastname: Zhang
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.forename: Leonid N
authors.initials: LN
authors.lastname: Maslov
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494828:Bax protein, rat; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C052064:astragaloside A; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: TLR4/NF-κB signaling pathway; apoptosis; astragaloside IV; inflammatory response; myocardial ischemia/reperfusion