Dactylorhin B reduces toxic effects of beta-amyloid fragment (25-35) on neuron cells and isolated rat brain mitochondria.
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.
Zhang
Dan
D
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhang
Yi
Y
Liu
Gengtao
G
Zhang
Jianjun
J
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D029595:Orchidaceae / Q000737:chemistry; D010446:Peptide Fragments / Q000633:toxicity*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013386:Succinates / Q000737:chemistry / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D005960:Glucosides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010446:Peptide Fragments; D010936:Plant Extracts; D011768:Pyruvate Dehydrogenase Complex; D017382:Reactive Oxygen Species; D013386:Succinates; C074636:amyloid beta-protein (25-35); C479293:dactylorhin B; D008315:Malondialdehyde; D045304:Cytochromes c; D007655:Ketoglutarate Dehydrogenase Complex; D000251:Adenosine Triphosphatases; D005978:Glutathione