23 September 2019 : Animal Research
Astragaloside IV Alleviates the Myocardial Damage Induced by Lipopolysaccharide via the Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB)/Proliferator-Activated Receptor α (PPARα) Signaling PathwayXiaoyao Zhang1ABCDEF*, Mengfei Li1AF, Hongxin Wang1ABCDEFG
Med Sci Monit 2019; 25:7158-7168
BACKGROUND: We previously reported that astragaloside IV (As-IV) can alleviate myocardial damage induced by lipopolysaccharide (LPS). However, the anti-inflammatory effects of As-IV following LPS stimulation in mice and H9C2 cardiomyocytes remain unclear. The present study was designed to explore the mechanism of action of As-IV.
MATERIAL AND METHODS: In vivo, C57BL/6J mice were randomly divided into 5 groups: the control group, the LPS group (10 mg/kg), and 3 LPS groups receiving different doses of As-IV (20, 40, and 80 mg/kg). The protective effect of As-IV on LPS-stimulated H9C2 cardiomyocytes was evaluated in vitro. Cardiac function was detected by echocardiography, and H&E staining was used to evaluate morphologic changes. Cardiomyocyte viability was detected by MTT assay. ELISA was used to detect free fatty acid (FFA), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) levels in mouse serum and in cell supernatant. Adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents in myocardial tissues and cells were detected by high-performance liquid chromatography. ATP5D and TLR4/NF-κB/PPARα signaling pathway proteins (TLR4, NF-κB, p65, and PPARα) were detected by Western blotting.
RESULTS: As-IV significantly improved cardiac function, myocardial cell viability, and pathological changes and reduced FFA, IL-1β, IL-6, and TNF-α levels. The ATP/AMP ratio in the cardiac tissues of mice and in H9C2 cardiomyocytes was increased compared to that in the LPS group. In addition, As-IV enhanced ATP synthase and PPARα protein expression. In H9C2 cardiomyocytes, the p65-specific inhibitor BAY11-7082 exerted similar effects as As-IV.
CONCLUSIONS: As-IV alleviates LPS-induced myocardial damage by modulating TLR4/NF-κB/PPARα signaling-mediated energy biosynthesis.
Keywords: Lipopolysaccharides, NF-kappa B, PPAR alpha, Toll-Like Receptor 4, Cell Survival, China, Heart, Interleukin-6, Mice, Inbred C57BL, Myocardium, Myocytes, Cardiac, Saponins, Signal Transduction, Triterpenes
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