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Studies On Anti-depressant Effects Of Aqueous Extract Of Acanthopanax Senticosus And Its Mechanism Of Action

Posted on:2011-10-14Degree:MasterType:Thesis
Country:ChinaCandidate:Q JiangFull Text:PDF
GTID:2144360305955558Subject:Biochemistry and Molecular Biology
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Depression is a psychosis, which is characterized by various manifestation of affective disorder. It affects patient's working,learning and living so that they have difficulty adapting themselves to society,even induced suicidal behavior at last. With intense social competition and fast working pace, more and more people will feel tensive, exhausted and melancholy. Incidence rate of depression will show an upward tendency. All though, the mechanisms of depression is not well known, extensive research has been demonstrated that chronic psychological stress may play a crucial role in the development of depression. Right now, the drugs used to treat on depression is mainly Western-style Pharmaceuticals which have a toxic effect on the worst failings. Today, the reach is focused on the pathogenesis of depression and the new drugs that have fewer side effect and effective affect.Acanthopanax senticosus(A. senticosus) belongs to the family Araliaceae and is a shrub found in northeast of China, korea, Japan and Russian. the root bark extract of this herb has been known for thousands of years as a remedy for psychophysical stress or fatigue.The roots and stems of A. senticosus have been also used to treat chronic diseases, such as chronic renal failure, rheumatics, diabetes mellitus, chronic bronchitis, hypertension, gastric ulcer and ischemic heart diseases. In our country, A. senticosus is known for thousands of years as a medicinal herb and has been clinically used to treat coronary heart disease,angia,ischemic stroke,diabete and hypertension. However, little is known about anti-depression effects of aqueous extract of A. senticosus and its mechanisms of action and provide the evidence for the clinical use.1,36 KM mice which were eight-weekly age were randomly divided into six group, the control group, the modle group and four prevention groups. Further, four prevention groups mice were classified into four group separately, DZP positive control group, low concentration, middle concentration and high concentration of aqueous extract of A. senticosus. Mice depression models were established by the elevated plus maze behavior test and the tail suspension test. To prevent neuronal damage, depression modle mice were administered by different dozes of aqueous extract of A. senticosus. The results showed that aqueous extract of A. senticosus significantly reduced the concentration of Cort in serum of the depression modle mice and increased the CREB protein in the cerebrum of the depression modle mice. The low concentration of aqueous extract of A. senticosus have significantly effect on the elevated plus maze behavior test and the middle concentration of aqueous extract of A. senticosus have significantly effect on the tail suspension test. All the results proved that aqueous extract of A. senticosus have preventive effect on depression state,because it can regulate the function of HP A and increase CREB in the cerebrum of mice.2,In this study, the effect of aqueous extract of A. senticosus on Cort-induced apoptosis(200μmol/L) was studied by using a rat pheochromocytoma (PC 12) cell line. We investigated the protective effects of aqueous extract of A. senticosus on Cort-induced neurotoxicity in PC 12 cells model by MTT and LDH assay. The results showed that Cort decreases the PC 12 cell viability in a dose-dependent manner and aqueous extract of A. senticosus have no effect on PC 12 cell viability. After treatment of PC 12 cells with aqueous extract of A. senticosus (0,25,50,100,200,400,800mg/L) on PC12 cells exposured by Cort, the Cort-induced cytoxicity was significantly attenuated. Furether, aqueous extract of A. senticosus can also maintain the plasma membrane integrity. Inverted microscope and Hoechst 33258 assays revealed the appearance of a collection of multiple chromatin and fragmented apoptotic nuclei upon Cort treatment. However, the incidence of apoptotic nuclei was significantly reduced when cells were treated with aqueous extract of A. senticosus. The apoptotic cells were analyzed quantified using flow cytometry. When PC 12 cells were concurrently treated with aqueous extract of A. senticosus, the percentage of apoptotic cells decreased from 17.9±3.87% to 14.8±3.16%. Compared to control, Cort can increase intracellular [Ca2+]i concentration in PC 12 cells, and aqueous extract of A. senticosus had the effect of decreasing PC 12 cells intracellular [Ca2+]i overload induced by Cort. Western bloy analysis showed that Cort can reduce the expression of CREB in PC 12 cells and aqueous extract of A. senticosus can increased significantly. On the basis of these finding, aqueous extract of A. senticosus have the protective effects on Cort-induced neurotoxicity. we speculate that the neuroprotectiveeffects of aqueous extract of A. senticosus may be achieved by the regulation of intracellular [Ca2+]i overload, as well as rasing the expression of CREB in PC 12 cells that play a key role in protecting neurons.
Keywords/Search Tags:Aqueous extract of A. senticosus, PC12 cells, Corticosterone, Depression, Neuroprotection
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