Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo, Japan.
Int J Mol Med. 2011 Jan;27(1):33-8. doi: 10.3892/ijmm.2010.554. Epub 2010 Nov 10.
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.
抗氧化黄酮类化合物被用于降低人类患心血管疾病的风险。然而，黄酮类化合物抗动脉粥样硬化作用的确切机制仍有待阐明。在本研究中，为了评估抗氧化黄酮类化合物对动脉粥样硬化作用的机制，我们研究了目前已知最有效的抗氧化剂之一 flavangenol 对自发性高脂血症 B6.KOR-Apoeshl 小鼠的影响。flavangenol 被自由给予 B6.KOR-Apoeshl 小鼠口服（每只小鼠 6 毫克 flavangenol/天）。6 个月后，测量血清脂质（总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇）和脂质过氧化物水平，并评估主动脉根部的组织病理学变化（脂质积聚和炎症细胞浸润）。与用作对照的 C57BL/6 小鼠相比，B6.KOR-Apoeshl 小鼠的血清总胆固醇和 LDL 胆固醇水平显著升高，而 HDL 胆固醇水平降低（p<0.001）。在这些血清脂质中，只有 HDL 胆固醇水平因 flavangenol 给药而显著升高（p<0.05）。此外，与 C57BL/6 小鼠相比，B6.KOR-Apoeshl 小鼠的油红 O 染色（脂质积聚）显著增加（p<0.001）。值得注意的是，flavangenol 给药显著抑制了油红 O 染色的增加（p<0.01）。同样，B6.KOR-Apoeshl 小鼠内膜炎症细胞浸润显著增加与 C57BL/6 小鼠相比（p<0.01），flavangenol 给药显著抑制炎症细胞浸润（p<0.01）。重要的是，flavangenol 给药显著降低了 B6.KOR-Apoeshl 小鼠血清脂质过氧化物水平的升高（p<0.05）。总之，这些观察结果表明，作为最有效的抗氧化剂之一的 flavangenol 对自发性高脂血症和动脉粥样硬化的 B6.KOR-Apoeshl 小鼠发挥其抗动脉粥样硬化作用，可能通过增加 HDL 胆固醇水平和降低脂质过氧化物水平，从而抑制主动脉根部内膜的脂质积聚（形成动脉粥样硬化病变）和炎症细胞浸润（慢性炎症）。
