Protective Effect Of Total Alkaloids From Pinellia Ternate Against Parkinsons Disease And Explore Its Mechanism

Parkinson’s disease is one ot neurodegenrative disease in aged and elderly people, mainly from degeneration of nigrostriatal dopaminergic neurons, it’s the second most common age-related neurodegenerative disease after Alzheimer’s disease. According to the epidemic survey, about six million people suffer from the disease in the worldwide, but at present clinical is still not completely clear to PD’s etiology and pathogenesis, for its treatment is still a worldwide problem. In recent years, researchers made a lot of progress to PD pathogenesis, mainly concentrated in the genetic factor, environmental factors, inflammatory immune mechanism, oxidative stress and cell apoptosis, more and more attention to the role of oxidative stress in PD by researchers. Research shows that, as the growth of the age, the brain proteins, lipids, nucleic acid oxidation metabolic speed up, and faster in the process of PD oxide, how to cambat oxidative stress of the nervous system to suppress apoptosis of neurons have gradually.Pinellia ternate is dry tuber of tian naxing plants Pinellia ternate(Thunb)Breit, a common Chinese traditional medicine, with the effect of drying dampness and resolving phlegm, jiangni Vomiting, new away. It contain alkaloids, organic acids, polysaccharide, protein and many kinds of components, and alkaloids is the one of main effective ingredient. There’s a study showed that it has the certain antioxidant effect for the central nervous system. Our reaserch is to explore whether TAPT can protect rats and PC12cells from the induced damage of6-OHDA. Chapter one:Effect of Total Alkaloids from Pinellia Ternate on PD rat:learning, memory and oxidative stressObjective:To explore treatment and anti-oxidation mechanism of Total Alkaloids from Pinellia Ternate(TAPT) to PD rat models.Methods:Through injection6-OHDA in brain established rat model of Parkinson’s disease, and also give TAPT preventive treatment. Test behavior of PD rats by the Morris water maze, chemical assay for measuring superoxide dismutase (SOD) activity, malondialdehyde (MDA), hydrogen peroxide (H2O2) and glutathione (GSH) content in the cerebral cortex and serum.Results:Compare with the normal group, PD rats escape latency were significantly longer (P<0.01), significantly reduced the number of cross-platform (P<0.01); and after treatment by TAPT, PD rats escape latency were significantly shorter (P<0.05, P<0.01), cross-platform significant increase in the number (P<0.01). In the PD model group, MDA, H2O2content increased, SOD, GSH level decreased (P<0.01) in cerebral cortex, serological results are the same (P<0.01); after treatment by TAPT, MDA, H2O2content was significantly reduced (P<0.01), GSH content in cortex, SOD activity increased significantly (P<0.01); In the TAPT treatment group, low concentrations, middle concentrations serum MDA level was not significant (P>0.05), high concentrations serum MDA decreased (P<0.01), H2O2in treatment groups were significantly decreased in serum (P<0.01), SOD activity, GSH content in the treated group significantly increased in serum (P<0.01).Conclusion:TAPT have the ability to improve the learning and memeroy, and have a role against rat nervous system degeneration, possibly through changes Parkinson’s rat cortical and serum SOD, GSH level, while inhibit of MDA and H2O2generated. Chapter two:Protective effect of Total Alkaloids from Pinellia Ternate on6-hydroxydopamine-induced PCI2cells and explore its mechanismObjective:To explore the protective effect and possible mechanism of Total Alkaloids from Pinellia Ternate on pheochromocytoma cell line(PC12cells) induced damage by6-hydroxydopamine.Methods:PD cell model was induced by addition of6-OHDA into PC12cells that were pretreated with different doses of TAPT. Cell viability, total superoxide dismutase(T-SOD) activity, the content of malondialdehyde(MDA) and hydroxy radical(·OH), and caspase-3activity were assayed by MTT and visible spectrometry, respectively. Cell apoptotic percentage, and the protein expression of Bax and Bcl-2were assayed by FCM and immunoblotting, respectively.Results:The cell viability of PC12cells treated with100μmol/L6-OHDA for24h was lower, the level of T-SOD and inhibit capability to·OH were lower, the content of MDA and caspase-3activity were higher as compared to the control group(P<0.05). Compared with the model group, the cell viability was higher, the level of T-SOD and inhibit capability to·OH were higher, the content of MDA and caspase-3activity were lower in TAPT of different doses group(P<0.05). The Bax expression was up-regulated in model group and Bcl-2expression was down-regulated, compared with the control group. Compared with the model group, the Bax protein expression was down-regulated and Bcl-2protein expression was up-regulated in TAPT groups.Conclusion:TAPT has certain inhibition on6-OHDA-induced PC12cell damage and apoptosis, improve T-SOD, the inhibition of·OH power and reduced the MDA content and Caspase-3activity, up-regulating Bc1-2protein expression and down-regulating Bax protein expression is one of the mechanisms.