title: Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling.
abstract: Hyperlipidemia aggravates myocardial ischemia/reperfusion (MI/R) injury through stimulating excessive inflammatory response. Therefore, blockade of inflammatory signal is a potential therapeutic management for MI/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from Carthamus tinctorius L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI/R combined with hyperlipidemia injury. High-fat diet induced hyperlipidemia worsened MI/R mediated heart injury (elevation of infarct size, CK-MB and LDH activity), activated TLR4 over-expression in hearts, released inflammatory cytokines (LPS, TNF-α and IL-1β) excessively. HSYA administration suppressed the over-expression of TLR4 and alleviated heart damage caused by MI/R complicated with hyperlipidemia. Furthermore, HSYA had little influence on MI/R injury in TLR4-knockout mice, which indicated that HSYA protected MI/R through TLR4 inhibition. In vitro, hypoxia/reoxygenation (H/R) coexisting with LPS model in neonatal rat ventricular myocytes (NRVMs) induced serious damage compared with H/R injury to NRVMs. HSYA decreased excessive secretion of inflammatory cytokines, down-regulated over-expression of TLR4 and NF-κB in H/R + LPS injured NRVMs. In conclusion, HSYA alleviated myocardial inflammatory injury through suppressing TLR4, offering an alternative medication for MI/R associated with hyperlipidemia.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Han
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Wenhuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Dongcheng
authors.initials: D
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Weirong
authors.initials: W
authors.lastname: Fang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011809:Quinones; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C085278:hydroxysafflor yellow A; D002599:Chalcone; D007770:L-Lactate Dehydrogenase