alisol-b-monoacetate and Inflammation

Previous studies have shown that Alisol B 23-acetate (23ABA) had potent liver-protection effects, however, its roles and potential mechanisms in carbon tetrachloride (CCl

Topics: Animals; Anti-Inflammatory Agents; Carbon Tetrachloride; Fibrosis; Glutamate-Cysteine Ligase; Glutathione; Inflammation; Liver Cirrhosis; Mice; Oxidative Stress; RNA, Messenger

Atherosclerosis (AS) is characterized by dyslipidemia and chronic inflammation. In the high-fat environment, the lipid metabolism of dendritic cells (DCs) is abnormal, which leads to abnormal immune function, promotes the occurrence of immune inflammatory reactions, and promotes the development of AS. Alisol B 23-acetate (23B) is a triterpenoid in the rhizomes of Alisma, which is a traditional Chinese medicine. Here, we identified cholesterol metabolism-related targets of 23B through a virtual screen, and further transcriptome analysis revealed that 23B can change antigen presentation and cholesterol metabolism pathways in cholesterol-loaded DCs. In vitro experiments confirmed that 23B promoted cholesterol efflux from ApoE

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cholestenones; Cholesterol; Cytokines; Dendritic Cells; Disease Models, Animal; Dyslipidemias; Humans; Hypercholesterolemia; Inflammation; Lipid Metabolism; Male; Mice; Signal Transduction; T-Lymphocytes, Regulatory; T-Lymphocytopenia, Idiopathic CD4-Positive

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.

Topics: Animals; China; Cholestenones; Drugs, Chinese Herbal; Endotoxemia; Heart Diseases; Inflammation; Interleukin-6; Lipopolysaccharides; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NADPH Oxidase 2; NADPH Oxidases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Reactive Oxygen Species; Sepsis; Signal Transduction; Toll-Like Receptor 4; Triterpenes; Tumor Necrosis Factor-alpha