Baicalein targets CD36 to prevent foam cell formation by suppressing the excessive uptake of oxLDL and accelerating ABCA1-mediated cholesterol efflux in oxLDL-induced THP-1 macrophages. (October 2022)

• Record Type: Journal Article
• Authors: Li, Jingda; Xiong, Tao; Wang, Tianqi; Wang, Meng; Wang, Chao; Yang, Fuyuan; Wang, Xudong; Tan, Zhijian; Sun, Wenlong
• Is Part Of: Journal of functional foods. Volume 97(2022)
• Publication Date: 2022-10
• Subjects: Baicalein -- CD36 -- Oxidized low-density lipoprotein -- ABCA1 -- Cholesterol efflux -- Macrophage foam cell formation; AS atherosclerosis -- CD36 cluster of differentiation 36 -- oxLDL oxidized low-density lipoprotein -- ABCA1 ATP-binding cassette transporter A1 -- ABCG1 ATP-binding cassette transporter G1 -- oxLig-1 7-ketocholesteryl-9-carboxynonanoate -- JNK c-Jun N-terminal kinase -- SRs scavenger receptors -- SR-A1 scavenger receptor class A type I -- LOX-1 lectin-like oxLDL receptor-1; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2022.105253
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Baicalein can prevent oxLDL-induced foam cell formation in THP-1 macrophages. Baicalein inhibits oxLDL uptake by preventing the binding of CD36 to oxLDL. The binding of baicalein to CD36 triggers the Src-JNK-ABCA1 signalling pathway. Baicalein enhances cholesterol efflux to avoid cholesterol accumulation. Abstract: Oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation plays an important role in atherosclerosis progression. Baicalein is a constituent of Scutellaria baicalensis. Herein, we investigated the effect of baicalein on macrophage foam cell formation and the underlying mechanism. The THP-1 macrophage foam cell was established by oxLDL stimulation and the effects of baicalein on cholesterol uptake and efflux were analysed by molecular docking, ELISA, immunofluorescence, western blot, the inhibitor and siRNA experiment. The results showed that baicalein suppressed oxLDL-induced cholesterol accumulation. Mechanistically, baicalein reduced oxLDL uptake through competitive inhibiting the binding of CD36 to the epitope structure of oxLDL. Moreover, the binding of baicalein to CD36 enhanced the cholesterol efflux via the CD36-Src-JNK-ABCA1 signalling pathway. Meanwhile, Src and JNK inhibitors reversed the baicalein-induced reduction in cholesterol accumulation. In conclusion, these findings suggested that baicalein as a food supplement could inhibit macrophage foam cell formation and play an anti-atherosclerosis effect.