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.
Keywords: 1,1-Diphenyl-2-picrylhydrazyl; 3-(4,5-Dimethylthiazol-zyl)-2,5-diphenyltetrazolium bromide; ABCA1; ATP-binding cassette transporter A1; Atherosclerosis; Cholesterol removal; DPPH; ECL; Foam cells; Gossypetin; LDL; LXRα; MTT; Oxidation; Oxidized low-density lipoprotein; PPARs; REM; SDS-PAGE; SR-As; TBARS; TBS; Tris-buffered saline; acLDL; acetylated LDL; class A scavenge receptors; enhanced chemiluminescence; liver-X receptor α; low-density lipoprotein; ox-LDL; oxidized LDL; peroxisome proliferator-activated receptors; relative electrophoretic mobility; sodium dodecyl sulfate polyacrylamide gel electrophoresis; thiobarbituric acid reactive substances.