Antioxidative
flavonoids are used to reduce the risk of
cardiovascular diseases in humans. However, the precise mechanism for the anti-atherosclerotic actions of
flavonoids remains to be elucidated. In the present study, to assess the mechanism for the action of antioxidative
flavonoids on
atherosclerosis, we investigated the effect of
flavangenol, one of the most potent
antioxidants currently known, on spontaneously hyperlipidemic B6.KOR-Apoeshl mice.
Flavangenol was orally administered to B6.KOR-Apoeshl mice ad libitum (6 mg
flavangenol/mouse/day). After 6 months, serum levels of
lipids (total
cholesterol,
triglyceride, HDL-
cholesterol and
LDL-cholesterol) and
lipid peroxide were measured, and histopathological changes (
lipid accumulation and inflammatory cell infiltration) in the aortic root were evaluated. Serum levels of total
cholesterol and
LDL-cholesterol were markedly increased, and
HDL-cholesterol levels were decreased in B6.KOR-Apoeshl mice compared to C57BL/6 mice used as a control (p<0.001). Among these serum
lipids, only
HDL-cholesterol levels were significantly increased by
flavangenol administration (p<0.05). Moreover,
Oil Red O staining (
lipid accumulation) was significantly increased in B6.KOR-Apoeshl mice compared to C57BL/6 mice (p<0.001). Notably,
flavangenol administration significantly suppressed the increase in
Oil Red O staining (p<0.01). Similarly, inflammatory cell infiltration into the intima was significantly increased in B6.KOR-Apoeshl mice compared to C57BL/6 mice (p<0.01), and
flavangenol administration significantly suppressed the inflammatory cell infiltration (p<0.01). Importantly,
flavangenol administration significantly reduced the increase of serum
lipid peroxide levels in B6.KOR-Apoeshl mice (p<0.05). Together, these observations indicate that
flavangenol, one of the most potent
antioxidants, exerts its anti-atherosclerotic action on spontaneously hyperlipidemic and atherosclerotic B6.KOR-Apoeshl mice, possibly by increasing
HDL-cholesterol levels and reducing
lipid peroxide levels, thereby suppressing the
lipid accumulation (formation of atherosclerotic lesions) and inflammatory cell infiltration (chronic
inflammation) in the intima of the aortic root.