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Article Publish Status: FREE
Abstract Title:

Ganoderic acid A inhibits ox-LDL-induced THP-1-derived macrophage inflammation and lipid deposition via Notch1/PPARγ/CD36 signaling.

Abstract Source:

Adv Clin Exp Med. 2021 Oct ;30(10):1031-1041. PMID: 34329545

Abstract Author(s):

Tao Wang, Huihe Lu

Article Affiliation:

Tao Wang

Abstract:

BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease, is a major contributor to deaths worldwide. Ganoderic acid A (GAA) has been widely applied for various diseases due to its excellent anti-inflammatory properties.

OBJECTIVES: To investigate the underlying mechanism of GAA inhibition of inflammation and lipid deposition in human monocyte (THP-1) cells.

MATERIAL AND METHODS: The Cell Counting Kit-8 (CCK-8) assay was used to assess the potential effect of GAA on the viability of THP-1 cells. The release of inflammatory cytokines and oxidative stress was measured using enzyme-linked immunosorbent assay (ELISA) and the corresponding kit, respectively. The levels of lipid deposition and total cholesterol (TC) were also evaluated. Next, the scavenger receptors and proteins in Notch1/PPARă/CD36 signaling were measured with western blot. As Notch1 was overexpressed in the THP-1 cells induced by oxidized low-density lipoprotein (ox-LDL), the above assays were performed again to confirm the underlying mechanism.

RESULTS: Ganoderic acid A suppressed ox-LDL-induced inflammation and oxidative stress in THP-1 cells. At the same time, it inhibited the TC level and lipid deposition. The effects of GAA on alleviating inflammation, oxidative stress and lipid accumulation were relieved after the overexpression of Notch1 in the treated cells, and the effects of GAA on alleviating inflammation, oxidative stress and lipid accumulation were diminished. The PPARă activator also weakened the effects of GAA on relieving inflammation, oxidative stress and lipid accumulation in ox-LDL-induced THP-1 cells.

CONCLUSIONS: Ganoderic acid A inhibits ox-LDL-induced macrophage inflammation and lipid deposition in THP-1 cells through Notch1/PPARă/CD36 signaling, which may provide theoretical guidance for the clinical applications of GAA in AS treatment.

Study Type : In Vitro Study

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