中药大黄的生化学研究.ⅪⅩ.蒽醌衍生物对线粒体呼吸链的抑制部位

BIOCHEMICAL STUDY OF CHINESE RHUBARB.ⅪⅩ.LOCALIZATION OF INHIBITION OF ANTHRAQUINONE DERIVATIVES ON THE MITOCHONDRIAL RESPIRATORY CHAIN

本实验结果表明:大黄素、大黄酸和芦荟大黄素是线粒体呼吸链电子传递的抑制剂。(1)三药对NADH脱氢酶有不同程度的抑制作用,(2)大黄素对琥珀酸脱氢酶有较强的抑制作用,而大黄酸和芦荟大黄素对此酶仅有轻微的抑制作用;(3)三药对辅酶Q-细胞色素C还原酶及细胞色素C氧化酶也仅有轻微的抑制作用;(4)动力学观察表明:三药对NADH脱氢酶的抑制均为竞争性的。

The effects of anthraquinone derivatives on the four electron transport complexes of mitochondron have been investigated. The results showed that emodin, rhein and aloe-emodin acted as inhibitors of some enzymes of the mitochondrial electron transport system.(1) Rhein, emodin and aloe-emodin specifically interfered with the redox function of the NADH dehydrogenase (complex Ⅰ). Rhein, emodin and aloe-emodin showed strongest, moderate and weak inhibition, respectively. The concentrations for 50% inhibition were 22 μg/ml, 38 μg/ml and 72 μg/ml, respectively.(2) The kinetics of the inhibition of rhein, emodin and aloeemodin on the membrane-bound NADH dehydrogenase was studied. The results indicated that the inhibition was competitive with respect to substrate, with Ki values of 35 μmol, 60 μmol and 110 μmol at 25℃, respectively.(3) Emodin significantly inhibited the activity of succinate dehydrogenase (complex Ⅱ). The concentration for 50% inhibition was 55 μg/ml, but aloe-emodin and rhein showed no marked effect on this enzyme.(4) Emodin, rhein and aloe-emodin showed no significant effect on coenzyme Q-cytochrome C reductase (complex Ⅲ) and cytochrome C oxidase (Complex Ⅳ).The results were in agreement with previous finding that emodin showed strongest antibacterial and anticancer activities, while rhein showed moderate effect and aloe-emodin showed only weak effect. It appears that inhibition of mitochondrial respiratory chain is one of the mechanisms of antibacterial and anticancer actions of Chinese rhubarb.