Zhang Dan, Zhang Yi, Liu Gengtao, Zhang Jianjun
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Nov;374(2):117-25. doi: 10.1007/s00210-006-0095-9. Epub 2006 Oct 5.
beta-amyloid is strongly implicated in Alzheimer's pathology, and mitochondria play an important role in neurodegenerative disorders. Dactylorhin B [short for bis(4-beta-D-glucopyranosyloxybenzyl)-2-beta-D-glucopyranosyl-2-isobutyltartrate (DHB)] is an active compound isolated from Coeloglossum viride. (L.) Hartm. var. bracteatum (Willd.) and may have neuroprotective effects. In the present study, we investigated the damage of rat brain mitochondrial function induced by beta-amyloid and the protective effect of DHB. Isolated rat brain mitochondria were incubated with amyloid-beta peptide (Abeta)(25-35) alone or together with DHB. reactive oxygen species production, pyruvate dehydrogenase complex activity, alpha-ketoglutarate dehydrogenase complex activity, cytochrome c oxidase activity, mitochondrial swelling, mitochondrial membrane potential and the release of cytochrome c from mitochondria were measured. Data showed that Abeta(25-35) directly disrupted mitochondrial function, inhibited the key enzymes and contributed to apoptosis and the deficiency of energy metabolism. Co-incubation of DHB attenuated Abeta(25-35)-induced pathological changes. The significance of DHB in the management of mitochondria-related disorders is discussed.
β-淀粉样蛋白与阿尔茨海默病的病理过程密切相关,线粒体在神经退行性疾病中起重要作用。双(4-β-D-吡喃葡萄糖氧基苄基)-2-β-D-吡喃葡萄糖基-2-异丁基酒石酸酯(DHB),简称指状兰素B,是从短距舌唇兰中分离出的一种活性化合物,可能具有神经保护作用。在本研究中,我们研究了β-淀粉样蛋白诱导的大鼠脑线粒体功能损伤以及指状兰素B的保护作用。将分离的大鼠脑线粒体单独与淀粉样β肽(Aβ)(25-35)或与指状兰素B一起孵育。测定活性氧生成、丙酮酸脱氢酶复合体活性、α-酮戊二酸脱氢酶复合体活性、细胞色素c氧化酶活性、线粒体肿胀、线粒体膜电位以及细胞色素c从线粒体的释放。数据表明,Aβ(25-35)直接破坏线粒体功能,抑制关键酶,导致细胞凋亡和能量代谢不足。指状兰素B共同孵育减弱了Aβ(25-35)诱导的病理变化。讨论了指状兰素B在治疗线粒体相关疾病中的意义。