Tanshinone IIA protects against subclinical lipopolysaccharide induced cardiac fibrosis in mice through inhibition of NADPH oxidase.

Abstract

Myocardial fibrosis plays a central role in the development of heart failure. It has been shown that recurrent exposure to subclinical lipopolysaccharide (LPS) increases mortality and induces cardiac fibrosis in mice, which is not mediated by the common renin-angiotensin system. LPS increased NADPH oxidase2 (NOX2) in isolated adult mouse cardiac fibroblasts and NOX2 may mediate LPS-induced cardiac fibrosis. Therefore, the current study was designed to delineate the role of NOX2 in LPS-induced fibrosis model and to investigate the preventive role of Tanshinone IIA (TIIA) on the development of cardiac fibrosis. The protective mechanism of TIIA was determined to be associated with the inhibition of NOX2, by comparing its effects with the NADPH oxidase inhibitor, apocynin. The results revealed remarkable effects of apocynin and TIIA on attenuating the development of myocardial fibrosis and fibrosis-related genes and mediators. Furthermore, TIIA and apocynin decreased the expression of NADPH oxidase subunits (NOX2 and P67phox) expression and the ROS levels. The anti-fibrotic effect of apocynin suggested that NOX2 inhibition may be a potential preventive strategy for attenuating the progression of LPS-induced cardiac fibrosis. Our results demonstrate that TIIA may be a potent agent against subclinical LPS-induced cardiac fibrosis in mice partially via inhibition of NADPH oxidase 2.

• Authors: Libing Huang, Juan Zhu, Man Zheng, Rong Zou, Yudi Zhou, Minghui Zhu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 60 Pg. 59-63 (Jul 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 29704740 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Abietanes
• Acetophenones
• Lipopolysaccharides
• Phosphoproteins
• Protective Agents
• Reactive Oxygen Species
• neutrophil cytosol factor 67K
• tanshinone
• acetovanillone
• CYBB protein, human
• Cybb protein, mouse
• NADPH Oxidase 2

Topics

• Abietanes (pharmacology, therapeutic use)
• Acetophenones
• Animals
• Cardiomyopathies (chemically induced, drug therapy, metabolism, pathology)
• Fibrosis
• Lipopolysaccharides
• Male
• Mice, Inbred C57BL
• Myocardium (metabolism, pathology)
• NADPH Oxidase 2 (antagonists & inhibitors, metabolism)
• Phosphoproteins (metabolism)
• Protective Agents (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)