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• W1940454059 endingPage "6365" @default.
• W1940454059 startingPage "6352" @default.
• W1940454059 abstract "Bioassay-guided evaluation shows that a deep sea-derived fungus, Spiromastix sp. MCCC 3A00308, possesses lipid-lowering activity. Chromatographic separation of a culture broth resulted in the isolation of 15 known depsidone-based analogues, labeled spiromastixones A-O (1-15). Each of these compounds was tested for its ability to inhibit oxidized low-density lipoprotein (oxLDL)-induced foam cell formation in RAW264.7 macrophages. Spiromastixones 6-8 and 12-14 significantly decreased oxLDL-induced lipid over-accumulation, reduced cell surface area, and reduced intracellular cholesterol concentration. Of these compounds, spiromastixones 6 and 14 exerted the strongest inhibitory effects. Spiromastixones 6 and 14 dramatically inhibited cholesterol uptake and stimulated cholesterol efflux to apolipoprotein A1 (ApoA1) and high-density lipoprotein (HDL) in RAW264.7 macrophages. Mechanistic investigation indicated that spiromastixones 6, 7, 12 and 14 significantly up-regulated the mRNA levels of ATP-binding cassette sub-family A1 (ABCA1) and down-regulated those of scavenger receptor CD36, while the transcription of ATP-binding cassette sub-family A1 (ABCG1) and proliferator-activated receptor gamma (PPARγ) were selectively up-regulated by 6 and 14. A transactivation reporter assay revealed that spiromastixones 6 and 14 remarkably enhanced the transcriptional activity of PPARγ. These results suggest that spiromastixones inhibit foam cell formation through upregulation of PPARγ and ABCA1/G1 and downregulation of CD36, indicating that spiromastixones 6 and 14 are promising lead compounds for further development as anti-atherogenic agents." @default.
• W1940454059 created "2016-06-24" @default.
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• W1940454059 date "2015-10-14" @default.
• W1940454059 modified "2023-10-15" @default.
• W1940454059 title "Spiromastixones Inhibit Foam Cell Formation via Regulation of Cholesterol Efflux and Uptake in RAW264.7 Macrophages" @default.
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• W1940454059 doi "https://doi.org/10.3390/md13106352" @default.
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