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Current Neuropharmacology

Author(s): Tingting Pi, Guangping Lang, Bo Liu and Jingshan Shi*

DOI: 10.2174/1570159X19666210809101945

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Protective Effects of Dendrobium nobile Lindl. Alkaloids on Alzheimer's Disease-like Symptoms Induced by High-methionine Diet

Page: [983 - 997] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) have potential benefits for AD

Object: The objective of this study has been to explore whether DNLA can improve AD-like symptoms induced by HMD.

Methods: Mice were fed with 2% HMD diet for 11 weeks; the DNLA20 control group (20 mg/kg), DNLA10 group (10 mg/kg), and DNLA20 group (20 mg/kg) were administered DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl staining. Levels of homocysteine (Hcy), beta-amyloid 1-42 (Aβ1-42), S-adenosine methionine (SAM) and S-adenosine homocysteine (SAH) were detected by ELISA. Immunofluorescence and western blotting (WB) were used to determine the expression of proteins. CPG island methylation levels were accessed by Methylation-specific PCR (MSP) and MethylTarget methylation detection.

Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence staining showed that DNLA alleviated neuron damage and reduced the 5-methylcytosine (5-mC), Aβ1-40 and Aβ1-42 levels. DNLA also decreased the levels of Hcy and Aβ1-42 in the serum, along with decreasing SAM/SAH level in the liver tissue. WB results showed that DNLA down-regulated the expression of amyloid-precursor protein (APP), presenilin-1 (PS1), beta-secretase-1 (BACE1), DNA methyltransferase1 (DNMT1), Aβ1-40 and Aβ1-42 proteins. DNLA also up-regulated the proteins expression of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes.

Conclusion: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.

Keywords: High methionine diet, Alzheimer's disease-like symptoms, DNA methylation, Dendrobium nobile Lindl. alkaloid, beta-amyloid, CPG.

Graphical Abstract

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