Abstract
Heart failure characterized by cardiac remodeling is a global problem. Angiotensin II (Ang II) induces cardiac inflammation and oxidative stress, which also is implicated in the pathophysiology of adverse collagen accumulation-induced remodeling. Kaempferol (KPF), a kind of flavonoid compounds, is capable of anti-inflammatory and antioxidant activities. However, the target of KPF still remains blurred. In this study, we investigated the effect of KPF on Ang II-induced collagen accumulation and explored the underlying mechanisms. Our results suggested that KPF prevented Ang II-induced cardiac fibrosis and dysfunction, in mice challenged with subcutaneous injection of Ang II. In culture cells, KPF significantly reduced Ang II-induced collagen accumulation. Furthermore, KPF remarkably decreased inflammation and oxidative stress in Ang II-stimulated cardiac fibroblasts by modulating NF-κB/mitogen-activated protein kinase and AMPK/Nrf2 pathways.
MeSH terms
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AMP-Activated Protein Kinases / metabolism
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Angiotensin II*
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Antioxidants / pharmacology*
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Cells, Cultured
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Collagen / metabolism
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Disease Models, Animal
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Fibrosis
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Heart Failure / chemically induced
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Heart Failure / drug therapy*
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Heart Failure / metabolism
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Heart Failure / physiopathology
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Inflammation Mediators / metabolism*
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Kaempferols / pharmacology*
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Male
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Mice, Inbred C57BL
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Mitogen-Activated Protein Kinases / metabolism
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Myocytes, Cardiac / drug effects*
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Myocytes, Cardiac / metabolism
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Myocytes, Cardiac / pathology
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NF-E2-Related Factor 2 / metabolism
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NF-kappa B / metabolism
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Oxidative Stress / drug effects*
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Rats, Sprague-Dawley
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Signal Transduction
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Ventricular Function, Left / drug effects*
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Ventricular Remodeling / drug effects*
Substances
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Anti-Inflammatory Agents
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Antioxidants
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Inflammation Mediators
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Kaempferols
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NF-E2-Related Factor 2
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NF-kappa B
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Nfe2l2 protein, rat
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Angiotensin II
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kaempferol
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Collagen
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Mitogen-Activated Protein Kinases
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AMP-Activated Protein Kinases