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

Abstract

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) had potential benefits for AD. Object: Whether DNLA can improve AD-like symptoms induced by HMD is to be explored. Method: 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 administrated with DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl stainings. 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. Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence stainings 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 decreased SAM/SAH levels in the liver tissue. WB results showed that DNLA down-regulated the expression of the 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 expression of the protein of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a, and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes. Conclusions: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.

Dietary Methionine via Dose-Dependent Inhibition of Short-Chain Fatty Acid Production Capacity Contributed to a Potential Risk of Cognitive Dysfunction in Mice

“…Moreover, the LM group had a higher DI in the NORT and increased time spent and distance traveled in the quadrant containing the hidden platform during the MWT, although the difference did not reach a significant level when compared with that of the NM group; statistical changes and higher learning and memory were observed between the mice of the LM and HM groups. Taken together, our results suggested that HM diets impaired cognitive function including spatial, nonspatial, and working memory, which were consistent with the previous study demonstrating that HM diets led to learning and memory dysfunction . However, although LM diets had positive effects on cognitive behaviors in mice, they did not reach a significant difference.…”

“…Taken together, our results suggested that HM diets impaired cognitive function including spatial, nonspatial, and working memory, which were consistent with the previous study demonstrating that HM diets led to learning and memory dysfunction. 49 However, although LM diets had positive effects on cognitive behaviors in mice, they did not reach a significant difference. Our previous study found that LM diets ameliorated memory and cognitive dysfunction caused by obesity in mice.…”

Experimental approaches for altering the expression of Abeta‐degrading enzymes

“…Some of the approaches stated in the previous section to increase NEP expression have also been found to increase IDE expression in AD-related experimental systems (Jiang et al, 2021;Leissring et al, 2003;Pi et al, 2022;Tian et al, 2009;Yang et al, 2015;Yang et al, 2020;Yin et al, 2017). The substrates for IDE are diverse; in addition to Aβ, they include insulin B chain, amylin, natriuretic peptide, glucagon, glucagon-like peptide, insulin growth factor I (IGF-I), IGF-II, and atrial natriuretic peptide (Shen et al, 2006).…”

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment

“…Sarsasapogenin-AA13 can convert pro-inflammatory M1 microglia into anti-inflammatory M2 microglia and increase the expression of IDE and NEP, thus reducing toxic substance deposition ( 167 ). A new kind of pectin RP02-1 extracted from the roots of Polygala Tenuifolia, pectin LBP1C-2 purified from the fruits of Lycium berries, Notoginseng Saponin Rg1(Rg1), Rb1 and ginsenoside F1 can up-regulate the expression of Aβ -degrading enzyme in a similar way ( 106 , 152 , 168 – 171 ) ( Table 4 ). LBP1C-2 and Rg1can also decrease the expression of APP, BACE1 and PS1 and increase the expression of α secretase(ADAM10) ( 172 ).…”