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-1β, and tumor necrosis factor (TNF)-α 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-1β, and TNF-α 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.

Keywords: Alisma, Sepsis, Toll-Like Receptor 4, NADPH Oxidase, Cholestenones, Drugs, Chinese Herbal, Endotoxemia, Interleukin-6, Lipopolysaccharides, Mitogen-Activated Protein Kinases, NADPH Oxidase 2, Phosphorylation