Abstract
Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids, including hesperidin, naringin and nobiletin, inhibited thrombogenesis and hypertension in stroke prone spontaneously hypertensive rats (SHRSP) by protecting the endothelium from the adverse effects of free radical formation. We have now further investigated the protective effects of myricetin and hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E (apoE) and lowdensity lipoprotein receptor (LDLR) deficient (Apoe-/- and Ldlr-/- double knockout) mice. Three groups of mice were fed high fat diet alone and high fat diet mixed with myricetin (100 mg/kg/day and 200 mg/kg/day) or glucosyl hesperidin (G-hesperidin; 250 mg/kg/day and 500 mg/kg/day) for 8 weeks. There were no differences in body weight related to administration of the flavonoids. Thrombotic tendency was assessed using a He-Ne laser technique in the murine cerebral pial vessels. In addition, atherogenesis was quantified histologically after dissection of the aorta from each mouse and staining with Oil Red O solution. The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p < 0.001). These findings demonstrated that daily intake of myricetin and hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids.
Highlights
Flavonoids are polyphenolic compounds present in substantial amounts in plants
We have further investigated the protective effects of myricetin and hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E and lowdensity lipoprotein receptor (LDLR) deficient (Apoe−/− and Ldlr−/− double knockout) mice
The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p < 0.001). These findings demonstrated that daily intake of myricetin and hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids
Summary
Flavonoids are polyphenolic compounds present in substantial amounts in plants. They exert multiple biological effects, including antioxidant activity [1] [2], anti-inflammatory [3] [4], anti-cancer [5] [6] and neuroprotective properties [7]. Lipid oxidation has been shown to be associated with disturbances in the structure and functional loss of cell membranes, and oxidative modification appears to be an important initial event for the pathogenesis of atherosclerosis [8]. Myricetin has been found to be effective in scavenging free radicals [11] [13] and inhibiting the formation of malondialdehyde (MDA) from arachidonic acid when lipids undergo peroxidation [14]
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