Baicalein Attenuates Angiotensin II-Induced Cardiac Remodeling via Inhibition of AKT/mTOR, ERK1/2, NF-κB, and Calcineurin Signaling Pathways in Mice

Autor: Ying Liu, Hui-Hua Li, Lina Song, Liqing Yu, Ai-Wu Wang, Yunlong Xia, Cui Tian, Xue Jiang, Qiu-Yue Han, Jie Miao, Hong-Xia Wang, Jie Du
Rok vydání: 2014
Předmět:
Male
medicine.medical_specialty
Time Factors
Calcineurin Inhibitors
Inflammation
Ventricular Function
Left
Proinflammatory cytokine
chemistry.chemical_compound
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Animals
Lipoxygenase Inhibitors
Phosphorylation
Protein kinase B
PI3K/AKT/mTOR pathway
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Ventricular Remodeling
business.industry
Angiotensin II
Myocardium
TOR Serine-Threonine Kinases
NF-kappa B
Fibrosis
Baicalein
Enzyme Activation
Mice
Inbred C57BL
Calcineurin
Disease Models
Animal
Oxidative Stress
Endocrinology
Gene Expression Regulation
chemistry
Flavanones
Hypertension
Cytokines
Hypertrophy
Left Ventricular
Inflammation Mediators
medicine.symptom
business
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: American Journal of Hypertension. 28:518-526
ISSN: 1941-7225
0895-7061
Popis: 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.
Databáze: OpenAIRE
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