{Reference Type}: Journal Article
{Title}: Gypenoside XVII inhibits ox-LDL-induced macrophage inflammatory responses and promotes cholesterol efflux through activating the miR-182-5p/HDAC9 signaling pathway.
{Author}: Deng WY;Zhou CL;Zeng MY;
{Journal}: J Ethnopharmacol
{Volume}: 319
{Issue}: 0
{Year}: 2024 Jan 30
{Factor}: 5.195
{DOI}: 10.1016/j.jep.2023.117070
{Abstract}: BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.