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Excessive inflammatory responses in the endocardium are related to progression of infectious endocarditis. This study aimed to investigate whether (Z)-7,4'-dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside (DHAG), a compound isolated from the endophytic fungus Penicillium citrinum of Bruguiera gymnorrhiza, could attenuate cell damage caused by lipoteichoic acid (LTA) in embryonic rat heart cells (H9c2). LTA-induced cell damage occurred in H9c2 cells and the protective effects of DHAG at different concentrations (1-10 µM) were assessed. Indicators of oxidative stress and inflammatory responses in H9c2 cells were measured. DHAG (1-10 µM) significantly attenuated LTA-induced damage in H9c2 cells, as evidenced by increased cell viability and mitochondrial membrane potential, decreased cytochrome c release and DNA fragmentation, inhibition of caspase-3 and -9 activity, and altered expression of apoptosis-related proteins. DHAG also decreased oxidative stress by increasing protein expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Furthermore, DHAG inhibited inflammatory responses by decreasing protein expression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs). DHAG exerted protective effects against LTA-induced cell damage, at least partially by decreasing oxidative stress and inhibiting inflammatory responses. Our results provide a scientific rational for developing DHAG as a therapy against infectious endocarditis.

lipoteichoic acid, apoptosis, oxidative stress, inflammatory response, (Z)-7, 4'-dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside, infectious endocarditis

NCBI PubMed ID: 32865061
Publication DOI: 10.1177/0300060519889716
Journal NLM ID: 0346411
Publisher: London: Sage Publications
Correspondence: Department of Structural Heart Disease, the First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China
Institutions: Xie X
Methods: ELISA, Western blotting, biological assays, RT-PCR, cell growth, enzymatic assay, determination of NO production, cytokine production, cell viability assay, optical density measurement, ROS measurement