title: Baicalein inhibits HMGB1 release and MMP-2/-9 expression in lipopolysaccharide-induced cardiac hypertrophy.
abstract: Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes. In addition, pretreatment with baicalein inhibited LPS-induced early (e.g., tumor necrosis factor-α (TNF-α) and interleukin-6) and late (e.g., high mobility group box 1 (HMGB1) pro-inflammatory cytokine release, inducible nitric oxide synthase (iNOS) expression and NO production. Finally, baicalein also significantly down-regulated the expression of MMP-2/-9 and attenuated HMGB1 translocation from the nucleus to the cytoplasm. These results suggest that baicalein can protect cardiomyocytes from LPS-induced cardiac injury via the inhibition of ROS and inflammatory cytokine production. These cardioprotective effects are possibly mediated through the inhibition of the HMGB1 and MMP-2/-9 signaling pathways.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan , Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan , Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Huai-Min
authors.initials: HM
authors.lastname: Chen
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Liou
authors.forename: Jong-Hau
authors.initials: JH
authors.lastname: Hsu
authors.forename: Tsan-Ju
authors.initials: TJ
authors.lastname: Chen
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Cheng
authors.forename: Chaw-Chi
authors.initials: CC
authors.lastname: Chiu
authors.forename: Jwu-Lai
authors.initials: JL
authors.lastname: Yeh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000378:metabolism*; D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D014176:Protein Biosynthesis / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D031364:Scutellaria baicalensis
chemical_list: D000975:Antioxidants; D044950:Flavanones; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C006680:baicalein; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Baicalein; Cardiac Hypertrophy; High Mobility Group Box 1; Lipopolysaccharide; Matrix Metalloproteinases; Reactive Oxygen Species