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 antiatherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of >50 mu M 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 Cu2+ -induced oxidation of LDL Gossypetin showed potential in reducing ox-LDLinduced 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 a (PPARa)/liver-X receptor a (LXR alpha)/ATP-binding cassette transporter Al (ABCA1) and PPAR gamma/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARa siRNA or PPAR gamma 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. C) 2013 Elsevier Inc. All rights reserved.