Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction by Suppressing Toll-Like Receptor 4 (TLR4)/NADPH Oxidase 2 (NOX2) Signaling Pathway.

BACKGROUND Cardiac dysfunction during endotoxemia is a major cause of cardiovascular disease with high morbidity and mortality. Alisol B 23-acetate (AB23A) is a triterpenoid extracted from the Rhizoma Alismatis, a kind of traditional Chinese medicine, exhibits anti-inflammatory activity on endotoxemia. This investigation aimed to uncover the protective effects of AB23A against sepsis-induced cardiac dysfunction. MATERIAL AND METHODS Adult male C57BL/6 mice received lipopolysaccharide (LPS) (20 mg/kg intravenous) stimulation, with or without pre-treatment of AB23A (10 mg/kg, 20 mg/kg, or 40 mg/kg). Histopathological staining and cardiac function were performed 4 hours after LPS stimulation. Then the levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-alpha were monitored with enzyme-linked immunosorbent assay (ELISA). In addition, H9C2 cells were treated with LPS (5 μg/mL) with or without pre-treated with AB23A (0.1 μM, 1 μM, or 10 μM), and the production of reactive oxygen species (ROS) was detected by DCFH-DA combined with flow cytometry. The expression of Toll-like receptor 4 (TLR4), NADPH oxidase 2 (NOX2), NOX4, P38, p-P38, extracellular-signal-regulated kinase (ERK), and p-ERK were assessed by western blotting. RESULTS AB23A improved the survival rate and ameliorated myocardial injury, decreased inflammatory infiltration and the level of IL-6, IL-1ß, and TNF-alpha in the LPS-stimulated mouse model. Moreover, AB23A inhibited the ROS production in LPS-treated H9C2 cells. In addition, AB23A suppressed the levels of TLR4 and NOX2 as well as the activation levels of P38 and ERK both in vivo and in vitro. CONCLUSIONS AB23A reduced LPS-induced myocardial dysfunction by inhibiting inflammation and ROS production through the TLR4/NOX2 pathway.