title: Baicalein attenuates angiotensin II-induced cardiac remodeling via inhibition of AKT/mTOR, ERK1/2, NF-κB, and calcineurin signaling pathways in mice.
abstract: BACKGROUND
  Baicalein, a specific lipoxygenase (LOX) inhibitor, has anti-inflammatory and antioxidant effects. However, the functional role of baicalein in angiotensin II (Ang II)-induced hypertension and cardiac remodeling remains unclear. Here we investigated the effect of baicalein on cardiac hypertrophy and fibrosis and the underlying mechanism.
  
  
  METHODS
  Wild-type (WT) mice were injected with Ang II (1,200ng/kg/min) alone or together with 12/15-LOX inhibitor baicalein (25mg/kg) for 14 days. Histological examinations were performed on heart sections with hematoxylin and eosin, Masson's trichrome, wheat germ agglutinin staining, and immunohistochemistry. The messenger RNA (mRNA) expression of cytokines and protein levels were detected by real-time polymerase chain reaction (PCR) and western blot analysis respectively.
  
  
  RESULTS
  Ang II infusion significantly increased blood pressure but decreased cardiac contractile function reflected by fractional shortening% and ejection fraction% compared with saline-treated mice. Moreover, Ang II infusion resulted in marked cardiac hypertrophy and fibrosis, promoted accumulation of macrophages and T cells, the expression of proinflammatory cytokines and malondialdehyde (MDA) production. However, these actions were markedly reversed by administration of baicalein in mice. Mechanistically, the protective effects of baicalein were associated with the inhibition of inflammation, oxidative stress, and multiple signaling pathways (AKT/mTOR, ERK1/2, nuclear factor-κB (NF-κB), and calcineurin) in the Ang II-treated mice.
  
  
  CONCLUSIONS
  This study demonstrates that baicalein can significantly ameliorate Ang II-induced hypertension and cardiac remodeling, and may be a novel therapeutic drug for prevention of hypertensive heart diseases.
authors.affiliation: Department of Pharmacy, Provincial Hospital Affiliated to Shandong University, Ji-nan, China; #These authors contributed equally to this work.
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Wang
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China; #These authors contributed equally to this work.
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Changqing University Science & Technology Park, Ji-nan, China;
authors.forename: Jie
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China;
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China;
authors.forename: Cui
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China;
authors.forename: Xue
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China;
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Han
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, USA;
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Beijing, China;
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China;
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China; Center for Prevention and Control of Non-communicable Chronic Diseases, School of Public Health, Dalian Medical University, Dalian, China. hhli1995@yahoo.com yunlong_xia@126.com.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000804:Angiotensin II; D000818:Animals; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005355:Fibrosis; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D065095:Calcineurin Inhibitors; D016207:Cytokines; D044950:Flavanones; D018836:Inflammation Mediators; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D000804:Angiotensin II; C006680:baicalein; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: 12/15-lipoxygenase; angiotensin II; baicalein; blood pressure; cardiac remodeling; hypertension; signaling pathways.