title: Apigenin attenuates heart injury in lipopolysaccharide-induced endotoxemic model by suppressing sphingosine kinase 1/sphingosine 1-phosphate signaling pathway.
abstract: Sepsis is a cluster of heterogeneous syndromes associated with progressive endotoxemic developments, ultimately leading to damage of multiple organs, including the heart. This study is to investigate the effects of apigenin on heart injury in lipopolysaccharide-induced endotoxemic rat model. Normal Wistar rats were randomly divided into four groups: control group, LPS group (15 mg/kg), LPS plus apigenin groups with different apigenin doses (50 mg/kg, 100 mg/kg). Serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) were measured after the rats were sacrificed. SphK1/S1P signaling pathway proteins, cleaved caspase-3, cleaved caspase-9, Bax and Bcl-2 in heart were measured by Western blot. In vitro, we evaluated the protective effect of apigenin on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Apigenin decreased serum levels of CK-MB, LDH, TNF-α, IL-6, IL-1β. SphK1/S1P signaling pathway proteins, cleaved caspase-3, cleaved caspase-9, Bax in heart were found inhibited and Bcl-2 increased in the apigenin groups in vivo. In addition, apigenin inhibited intracellular calcium, the MAPK pathway and SphK1/S1P signaling pathway in vitro. Apigenin exerts pronounced cardioprotection in rats subjected to LPS likely through suppressing myocardial apoptosis and inflammation by inhibiting the SphK1/S1P signaling pathway.
authors.affiliation: Changchun University of Chinese Medicine, Changchun 130117, China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Zhang
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China. Electronic address: yantianhuabest@126.com.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
authors.affiliation: School of Life Science, Peking University, Beijing 100871, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Changchun University of Chinese Medicine, Changchun 130117, China. Electronic address: wangshuminch@126.com.
authors.forename: Shumin
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Science, Peking University, Beijing 100871, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D047310:Apigenin / Q000627:therapeutic use*; D002460:Cell Line; D019446:Endotoxemia / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006321:Heart / Q000187:drug effects; D006335:Heart Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides; D008246:Lysophospholipids / Q000276:immunology*; D008297:Male; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology; D000099157:Sphingosine Kinase
chemical_list: D000893:Anti-Inflammatory Agents; D047310:Apigenin; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate
keywords: Apigenin; Endotoxemic heart; SphK1/S1P signaling pathway