INHIBITION OF MITOCHONDRIAL RESPIRATION AND CYANIDE-STIMULATED GENERATION OF REACTIVE OXYGEN SPECIES BY SELECTED FLAVONOIDS
INHIBITION OF MITOCHONDRIAL RESPIRATION AND CYANIDE-STIMULATED GENERATION OF REACTIVE OXYGEN SPECIES BY SELECTED FLAVONOIDS
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DOI：
10.1016/0006-2952(94)90190-2
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发表时间：
1994-02-09
影响因子：
5.8
通讯作者：
PARDINI, RS
中科院分区：
文献类型：
--
作者：
HODNICK, WF;DUVAL, DL;PARDINI, RS
我们对具有不同羟基环构型的黄酮类化合物进行了结构活性研究的继续。我们测试了另外六种黄酮类化合物抑制牛心线粒体琥珀氧化酶和 NADH 氧化酶活性的能力。在每种情况下，观察到的 NADH 氧化酶系统的 IC50 均低于琥珀氧化酶活性，表明主要抑制位点位于呼吸链的复合物 I（NADH-辅酶 Q 还原酶）部分。抑制 NADH 氧化酶活性的效力顺序为刺槐素、鼠李素、泽兰素、黄芩素、7,8-二羟基黄酮和去甲汉黄素，IC50 值分别为 19、42、43、77、277 和 340 nmol/mg 蛋白质。具有相邻三羟基或对二羟基基团的黄酮类化合物表现出显着的自动氧化速率，添加氰化物（CN-）会加速这种自动氧化速率。具有儿茶酚构型的类黄酮在缓冲液中表现出缓慢的自动氧化速率，该氧化速率受到添加CN-的刺激。在自氧化实验中添加超氧化物歧化酶(SOD)和过氧化氢酶均降低了耗氧速率，表明自氧化过程中产生了O-2(-)和H2O2。在CN-刺激的氧化实验中，SOD的添加也减慢了氧消耗的速度。这些发现表明 CN-/类黄酮相互作用以非酶促方式产生 O-2(-)，这可能具有生物学意义。
A continuation of our structure-activity study on flavonoids possessing varied hydroxyl ring configurations was conducted. We tested six additional flavonoids for their ability to inhibit beef heart mitochondrial succinoxidase and NADH-oxidase activities. In every case, the IC50 observed for the NADH-oxidase enzyme system was lower than for succinoxidase activity, demonstrating a primary site of inhibition in the complex I (NADH-coenzyme Q reductase) portion of the respiratory chain. The order of potency for inhibition of NADH-oxidase activity was robinetin, rhamnetin, eupatorin, baicalein, 7,8-dihydroxyflavone, and norwogonin with IC50 values of 19, 42, 43, 77, 277 and 340 nmol/mg protein, respectively. Flavonoids with adjacent tri-hydroxyl or para-dihydroxyl groups exhibited a substantial rate of auto-oxidation which was accelerated by the addition of cyanide (CN-). Flavonoids possessing a catechol configuration exhibited a slow rate of auto-oxidation in buffer that was stimulated by the addition of CN-. The addition of superoxide dismutase (SOD) and catalase in the auto-oxidation experiments each decreased the rate of oxygen consumption, indicating that O-2(-) and H2O2 are generated during auto-oxidation. In the CN--stimulated oxidation experiments, the addition of SOD also slowed the rate of oxygen consumption. These findings demonstrate that the CN-/flavonoid interaction generated O-2(-) non-enzymatically, which could have biological implications.