ABSTRACT
Because of the proposed importance of mitochondrial cytochrome C oxidase (COX) decrease in Alzheimer's disease (AD) , the protective effect of Shenwu capsule on mitochondrial deficiency model rats and its pharmacological mechanism were investigated in present study. Rats were administered with azide at 1 mg . kg-1 . h-1 subcutaneously via an Alzet minipump for 30 days. Tweny-four hours after the operation, the rats were administered intragastrically by Shenwu capsule with the dose of 0. 45, 0. 9 and 1. 8 g . kg-1 . d-1 for one month. Then learning-memory ability was determined by the watermaze test and passive avoidance tests. The activity of choline-acetyl-transfertase(ChAT) and acetylcholinesterase (AChE) in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. M-cholinergic receptor binding ability (M-binding) was assayed by radio binding. Chronic infusion of sodium azide via minipump induced learning-memory deficiency of rats. Both ChAT activity and M-binding decreased in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. As the result, the cholinergic function of the brain decreased in model rats. Shenwu capsule significantly improved learning and memory ability and the mechanism may be related with the improved cholinergic function in model brain: ChAT activity and M-binding significantly increased in Shenwu treated groups compared with model group; and the increased activity of AChE in hippocampus returned to normal. Mitochondria, especially mitochondrial cytochrome C oxidase, may play the key role in the early event of AD. Chronic, partial in vivo inhibition of mitochondrial cytochrome C oxidase in rats provides a suitable model mimicking several aspects of AD. Shenwu capsule indicate effectiveness in AD-like mitochondrial deficiency model rats, so it would be applied in the treatment of AD.
Subject(s)
Animals , Rats , Acetylcholinesterase , Metabolism , Alzheimer Disease , Drug Therapy , Brain , Metabolism , Drugs, Chinese Herbal , Therapeutic Uses , Electron Transport Complex IV , Metabolism , Learning , Memory , Mitochondria , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of the new Traditional Chinese Compound Shenwu Capsule on the damage of lymphocyte DNA and lipid peroxidation in peripheral blood of rats induced by beta-amyloid injection.</p><p><b>METHOD</b>The animal model was made by injection of beta-amyloid25-35 into hippocampus of rats. DNA damage of lymphocytes was measured by the single cell gel electrophoresis (SCGE) combined with the laser scanning confocal microscopy (LSCM). The content of malondialdehyde (MDA) was determined by TBA assay.</p><p><b>RESULT</b>Shenwu Capsule decreased the rate of the comet-like cell, comet-like cell lengh (TCL), and tail moment (TM) of lymphocytes in peripheral blood of model rats. Shenwu Capsule also declined the MDA content in serum of Abeta model rats.</p><p><b>CONCLUSION</b>Shenwu Capsule has protective effect on peripheral blood lymphocyte DNA.</p>
Subject(s)
Animals , Male , Rats , Amyloid beta-Peptides , Capsules , DNA Damage , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Lymphocytes , Neurodegenerative Diseases , Pathology , Neuroprotective Agents , Pharmacology , Panax , Chemistry , Plants, Medicinal , Chemistry , Polygonum , Chemistry , Pueraria , Chemistry , Rats, Sprague-DawleyABSTRACT
Objective: To investigate the effect of taurine on learning and memory impairment, cytokines secretion in rats intrahippocampally injected with ?-amyloid (A?) 1-40. Methods: SD rats were randomly divided into control group, A? injected group, taurine (0.3g/kg?d, 0.6g/kg?d) groups. The rats were fed with taurine for 7 days, and then subjected to bilateral intrahippocampus injection of A?1-40 or vehicle. Two weeks later, all rats performed Morris water maze test. The contents of IL-6, TNF-? were checked by way of radio-immunity assay for hippocampus samples. Results: Compared with A?model group, the escape latency and distance were significantly reduced in taurine (0.6g/kg?d) group; the ratio of swimming distance in the target quadrant to that in the whole pool of the probe trial; the content of cytokines of IL-6 and TNF-?in hippocampus were reduced significantly. Conclusion: Taurine can effectively attenuate the cognitive dysfunction caused by A?1-40 in rats. The reduced cytokines content in hippocampus might contribute to this effect.