title: Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK.
abstract: Osthole, the active constituent of Cnidium monnieri extracts, has been shown to have a diverse range of pharmacological properties. In the present study, we aimed to evaluate the cardioprotective effects of osthole in a rat model of acute myocardial infarction (AMI). The rats with AMI were treated with 1, 3 and 10 mg/kg of osthole or the vehicle for 4 weeks. The infarct size of the rats with AMI was measured, and casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in the rats with AMI were analyzed using commercially available kits. The nuclear factor-κB (NF-κB), tumor necrosis factor‑α (TNF-α), interleukin (IL)-1β and IL-6 levels in whole blood from rats with AMI were also detected using commercially available kits. The levels of Toll-like receptors 2/4 (TLR2/4) and nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) were also detected by RT-qPCR. Moreover, the protein expression levels of endothelial nitric oxide synthase (eNOS) and mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, cyclooxygenase-2 (COX-2), as well as matrix metalloproteinase-2 (MMP-2) were all assayed by western blot analysis. Our results revealed that osthole markedly reduced the infarct size, and the levels of CK, CK-MB, LDH and cTnT in the rats with AMI, and that these cardioprotective effects may be associated with the inhibition of inflammatory reactions, the reduction in MMP-2 activity and the activation of MAPK cascades.
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Dou
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Tan
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D031048:Cnidium / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000097:blood / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D003374:Coumarins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C512493:NOD2 protein, rat; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; C046627:osthol