Luiz da Silva E, Tsushida T, Terao J
National Food Research Institute, Ministry of Agriculture, Forestry, and Fisheries, Ibaraki, Japan.
Arch Biochem Biophys. 1998 Jan 15;349(2):313-20. doi: 10.1006/abbi.1997.0455.
Lipoxygenase is suggested to be involved in the early event of atherosclerosis by inducing plasma low-density lipoprotein (LDL) oxidation in the subendothelial space of the arterial wall. Since flavonoids such as quercetin are recognized as lipoxygenase inhibitors and they occur mainly in the glycoside form, we assessed the effect of quercetin and its glycosides (quercetin 3-O-beta-glucopyranoside, Q3G; quercetin 4'-O-beta-glucopyranoside, Q4'G; quercetin 7-O-beta-glucopyranoside, Q7G) on rabbit reticulocyte 15-lipoxygenase (15-LOX)-induced human LDL lipid peroxidation and compared it with the inhibition obtained by ascorbic acid and alpha-tocopherol, the main water-soluble and lipid-soluble antioxidants in blood plasma, respectively. Quercetin inhibited the formation of cholesteryl ester hydroperoxides (CE-OOH) and endogenous alpha-tocopherol consumption effectively throughout the incubation period of 6 h. Ascorbic acid exhibited an effective inhibition only in the initial stage and LDL preloaded with fivefold alpha-tocopherol did not affect the formation of CE-OOH compared with the native LDL. CE-OOH formation was inhibited by both quercetin and quercetin monoglucosides in a concentration-dependent manner. Quercetin, Q3G, and Q7G exhibited a higher inhibitory effect than Q4'G (IC50: 0.3-0.5 microM for quercetin, Q3G, and Q7G and 1.2 microM for Q4'G). While endogenous alpha-tocopherol was completely depleted after 2 h of LDL oxidation, quercetin, Q7G, and Q3G prevented the consumption of alpha-tocopherol. Quercetin and its monoglucosides were also exhausted during the LDL oxidation. These results indicate that quercetin glycosides as well as its aglycone are capable of inhibiting lipoxygenase-induced LDL oxidation more efficiently than ascorbic acid and alpha-tocopherol.
脂氧合酶被认为通过在动脉壁内皮下空间诱导血浆低密度脂蛋白（LDL）氧化而参与动脉粥样硬化的早期事件。由于槲皮素等类黄酮被认为是脂氧合酶抑制剂，且它们主要以糖苷形式存在，因此我们评估了槲皮素及其糖苷（槲皮素3 - O - β - 吡喃葡萄糖苷，Q3G；槲皮素4'- O - β - 吡喃葡萄糖苷，Q4'G；槲皮素7 - O - β - 吡喃葡萄糖苷，Q7G）对兔网织红细胞15 - 脂氧合酶（15 - LOX）诱导的人LDL脂质过氧化的影响，并将其与分别由血浆中主要的水溶性和脂溶性抗氧化剂抗坏血酸和α - 生育酚所获得的抑制作用进行比较。在6小时的孵育期内，槲皮素有效地抑制了胆固醇酯氢过氧化物（CE - OOH）的形成和内源性α - 生育酚的消耗。抗坏血酸仅在初始阶段表现出有效抑制作用，与天然LDL相比，预加载五倍α - 生育酚的LDL对CE - OOH的形成没有影响。槲皮素和槲皮素单糖苷均以浓度依赖性方式抑制CE - OOH的形成。槲皮素、Q3G和Q7G表现出比Q4'G更高的抑制作用（IC50：槲皮素、Q3G和Q7G为0.3 - 0.5微摩尔，Q4'G为1.2微摩尔）。虽然LDL氧化2小时后内源性α - 生育酚完全耗尽，但槲皮素、Q7G和Q3G可防止α - 生育酚的消耗。在LDL氧化过程中，槲皮素及其单糖苷也会耗尽。这些结果表明，槲皮素糖苷及其苷元比抗坏血酸和α - 生育酚更能有效地抑制脂氧合酶诱导的LDL氧化。
