Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation.
Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of >50μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu(2+)-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent.
['Chen|Jing-Hsien|JH|', 'Tsai|Chia-Wen|CW|', 'Wang|Chi-Ping|CP|', 'Lin|Hui-Hsuan|HH|']
D000818:Animals D050197:Atherosclerosis D001713:Biphenyl Compounds D018929:Cell Culture Techniques D002460:Cell Line D002470:Cell Survival D024202:Electrophoretic Mobility Shift Assay D005419:Flavonoids D005487:Foam Cells D016166:Free Radical Scavengers D006801:Humans D015227:Lipid Peroxidation D008077:Lipoproteins, LDL D051379:Mice D010851:Picrates D017392:Thiobarbituric Acid Reactive Substances
Gossypetin LDL Oxidation Foam cells 1,1-Diphenyl-2-picrylhydrazyl DPPH thiobarbituric acid reactive substances TBARS relative electrophoretic mobility REM oxidized LDL ox-LDL peroxisome proliferator-activated receptors ABCA1 PPARs Cholesterol removal Atherosclerosis 3-(4,5-Dimethylthiazol-zyl)-2,5-diphenyltetrazolium bromide ATP-binding cassette transporter A1 ECL LXRα MTT Oxidized low-density lipoprotein SDS-PAGE SR-As TBS Tris-buffered saline acLDL acetylated LDL class A scavenge receptors enhanced chemiluminescence liver-X receptor α low-density lipoprotein sodium dodecyl sulfate polyacrylamide gel electrophoresis