Lonicera caerulea berry polyphenols activate SIRT1, enhancing the inhibition of Raw264.7 macrophage foam cell formation and promoting cholesterol efflux.
J Agric Food Chem. 2019 May 30. Epub 2019 May 30. PMID: 31146527
Lonicera caerulea berry polyphenols (LCBP) are known to reduce cholesterol accumulation. Currently, it is unknown whether LCBP can activate Sirtuin 1 (SIRT1) to regulate the formation of RAW264.7 macrophage foam cells. In this study, the effect of LCBP on lipid accumulation in macrophages was evaluated. Fluorescently labeled ox-LDL and 25-NBD cholesterol were used to detect the ox-LDL uptake and cholesterol outflow rate from macrophages. Gene silencing was performed using siRNA to detect changes in the expression of the ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding protein 2 (SREBP2), and SIRT1 proteins using western blotting, and changes in the expression of miR-33 were detected by real-time PCR. The results showed that treatment with 80μg/mL LCBP significantly inhibited the accumulation of lipids in RAW264.7 macrophages induced by ox-LDL and reduced intracellular cholesterol levels by activating SIRT1 to enhance the expression of ABCA1, a cholesterol efflux gene, but not independent effect. Of the three key LCBP components investigated, chlorogenic acid was found to activate SIRT1 and regulate the expression of the cholesterol-related factors ABCA1, SREBP2, and miR-33; cyanidin-3-glucoside and catechins were effective to a lesser extent. Our results suggest a novel hypolipidemic mechanism of LCBP.