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The Effects of Dendrobium Nobile Lindl.Alkaloids(DNLA)on α,β and γ-secretase of Hippocampal Neurons in SD Rat
Objective:Alzheimer's disease(AD)is a chronic neurodegenerative disorder characterized by the neuropathological conclusion of intracellular neurofibrillary tangles and extracellular amyloid plaque accumulation in vulnerable regions of the brain. The accumulation of amyloid-β peptides(Aβ)plays a key role in AD pathogenesis. The molecular culprit in AD is the Aβ,which derives from the amyloid precursor protein(APP)through sequential cleavage by the two proteasesβ- andγ-secretase. In contrast,α-secretase cleaves APP within the Aβdomain,thus preventing Aβgeneration. In this study,we tried to investigate the effects of Dendrobium nobile Lindl. Alkaloids (DNLA)on α,βandγ-secretase of hippocampal neurons in SD Rat. Methods:Primary hippocampal neurons of rat were cultured till the 8th day. Neurons purity was detected by immunofluorescence technique. The neurons were exposed to DNLA(0.35,3.5,35,350,700 ng·mL-1,respectively), then cultured for another 48 h and used for further detection. The cells activity was measured by methylthiazoldiphenyl tetrazolium(MTT)assay. Western blot measured the protein expression of APP,α-secretase(ADAM10 and ADAM17),β-secretase(BACE1),γ-secretase(PS1)and Aβ42. Results:Neurons purity was,at least,84.5％. The cell activity of viable hippocampal neurons was not changed significantly after the treatment with DNLA. However,DNLA reduced the protein expression of APP, ADAM10,BACE1 and Aβ42 of hippocampal neurons,increased the protein expression of ADAM17 and PS1,but the PS1 not significantly. Conclusion:DNLA reduced the protein expression of APP, ADAM10,BACE1 of hippocampal neurons in rat,increased the protein expression of ADAM17. And then reduced the protein expression of Aβ42. It suggests that DNLA has a potential health care value.
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The Effect of Dendrobium Nobile Lindl.Alkaloids on the Protein Expression of Aβ42,APP and BACE1 of Hippocampus in db/db Mice
Objective:Beta-amyloid(Aβ)deposition is considered as vital factor leading to cognitive impairment in Alzheimer's disease(AD).In addition,there are pathophysiological connections between Type 2 Diabetes Mellitus(T2DM)and AD. Diabetic patients have higher incidences of cognitive impairment and hence they are more at the risk of developing AD. As one of the active compounds of Dendrobium nobile Lindl. Dendrobium nobile Lindl. Alkaloids(DNLA)has the effect of protecting the nervous system and decreased the level of fasting blood glucose(FBG)in T2DM model mice. In this study,we attempted to investigate effects of DNLA on the proteins expression of APP,BACE1 and Aβ42 of hippocampus in db/db mice. Methods:10 male C57BL/KsJ mice were control group. And 4-week-old mice male db/db mice were randomly divided into four groups:model, DNLA-L(20 mg·kg-1),DNLA-M(40 mg·kg-1),and DNLA-H(80 mg·kg-1),there are 9 mice in each group. After mice were treated with different concentration DNLA by gavaged for 17 weeks. The protein expression ofβ-amyloid 42(Aβ42),β-site amyloid precursor protein-cleaving enzyme 1(BACE1)and amyloid precursor protein(APP)were examined by Western Blotting. Results:Compared with control group,not only the protein expression of Aβ42,but also BACE1 and APP was significantly increased in hippocampus of model group. Moreover,DNLA significantly decreased the protein expressions of Aβ42,BACE1 and APP in hippocampus of db/db mice compared with model group,and decreased in a dose-dependent manner. Conclusion:DNLA can decrease the protein expressions of Aβ42 in hippocampus of db/db mice. And the mechanism may be involved the decrease of BACE1 and APP.
