Gypenoside XVII inhibits ox-LDL-induced macrophage inflammatory responses and promotes cholesterol efflux through activating the miR-182-5p/HDAC9 signaling pathway

• Published in: Journal of ethnopharmacology Vol. 319; no. Pt 1; p. 117070
• Main Authors: Deng, Wen-Yi, Zhou, Cheng-Long, Zeng, Meng-Ya
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 30.01.2024
• Subjects: ABC transporters; ABCA1; atherosclerosis; bioinformatics; cell viability; cholesterol; cytokines; drugs; foam cells; foams; genes; Gynostemma pentaphyllum; Gypenoside XVII (GP-17); HDAC9; immunoblotting; Inflammation; Lipid deposition; luciferase; Macrophage; phenotype; prediction; quantitative polymerase chain reaction; risk; traditional medicine; ABCA1; Inflammation; Lipid deposition; HDAC9; Gypenoside XVII (GP-17); Macrophage
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2023.117070

The deposition of lipids in macrophages and the subsequent formation of foam cells significantly increase the risk of developing atherosclerosis (As). Targeting ATP-binding cassette transporter A1/G1 (ABCA1/ABCG1)-mediated reverse cholesterol transport is crucial for regulating foam cell formation. Therefore, the search for natural chemical components with the ability to regulate ABCA1/G1 is a potential drug target to combat the development of atherosclerosis. Gypenoside XVII (GP-17), a gypenoside monomer extracted from gynostemma pentaphyllum, presents an efficient anti-atherosclerosis function. However, the suppressed formation mechanism of foam cells by GP-17 remains elusive. To explore the protective activities of GP-17 in ox-LDL-induced THP-1 macrophage-derived foam cells through modulating the promotion of cholesterol efflux and alleviation of inflammation. MTT was used to detect cell viability. Bodipy493/503 and oil red O staining were performed to measure cell lipid deposition. Enzymatic assay was used to measure intracellular cholesterol measurement. Cholesterol efflux/uptake were determined by cholesterol efflux assay and Dil-ox-LDL uptake assay. Inflammatory cytokines were measured by ELISA. Bioinformatics prediction and dual luciferase reporter assay were performed to validate miR-182–5p targeting HDAC9. Relative protein levels were evaluated by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Our results showed that GP-17 upregulated the expression of ABCA1, ABCG1 and miR-182–5p, but reduced HDAC9 expression levels in lipid-loaded macrophages, which promoted cholesterol efflux and inhibited lipid deposition. Additionally, GP-17 promoted the M2 phenotype of the macrophage and suppressed the inflammatory response in THP-1 macrophage-derived foam cells. Overexpression of HDAC9 or suppression of miR-182–5p eliminated the effects of ABCA1/G1 expression, lipid deposition and pro-inflammatory response. These findings suggest that GP-17 exerts a beneficial effect on macrophage lipid deposition and inflammation responses through activating the miR-182–5p/HDAC9 signaling pathway. [Display omitted]