Longan (Dimocarpus longan Lour.) Aril ameliorates cognitive impairment in AD mice induced by combination of D-gal/AlCl3 and an irregular diet via RAS/MEK/ERK signaling pathway

J Ethnopharmacol. 2021 Mar 1:267:113612. doi: 10.1016/j.jep.2020.113612. Epub 2020 Nov 26.

Abstract

Ethnopharmacological relevance: According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as "forgetfulness" or "dementia", and it can be caused by spleen deficiency. Longan Aril (the aril of Dimocarpus longan Lour., LA) is a kind of Chinese medicine, and it can improve intelligence attributed to entering the spleen-meridian. This study aimed to explore the therapeutic effects of LA on AD mice with spleen deficiency, and to understand anti-AD mechanism of LA.

Material and methods: A mouse model of AD with spleen deficiency was established by D-gal (140 mg/kg, intraperitoneal injection) and AlCl3 (20 mg/kg, intragastrical administration) in combination with an irregular diet for 60 days, in which mice in LA group were daily given LA (0.5, 1.0 or 2.0 g/kg). The anti-AD effects of LA were evaluated by the Morris water maze, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E), Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The anti-AD mechanism of LA was studied by using metabolomics, and the expressions of RAS/MEK/extracellular signal-regulated kinase (ERK) signaling pathway-related proteins were detected by Western blotting.

Results: LA improved learning and memory abilities, superoxide dismutase (SOD) level, and form and number of Nissl bodies, while reduced the levels of Aβ42, phosphorylated-tau (p-tau), reactive oxygen species (ROS), malondialdehyde (MDA), monoamine oxidase-B (MAO-B), histological injury, and apoptosis rate in AD group (P < 0.05, P < 0.01 or P < 0.001). The anti-AD mechanism of LA may be related to RAS/MEK/ERK and other signaling pathways, in which the expressions of RAS/MEK/ERK signaling pathway-related proteins significantly reduced (P < 0.05 or P < 0.01).

Conclusions: LA could improve the cognitive ability and reduce the pathologic impairment in AD mice, which might be partly mediated via inhibition of RAS/MEK/ERK singling pathway.

Keywords: Alzheimer's disease (AD); Longan aril (LA); Neuroprotective; RAS/MEK/ERK singling Pathway; Spleen deficiency.

MeSH terms

  • Aluminum Chloride
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / prevention & control*
  • Alzheimer Disease / psychology
  • Animals
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / physiopathology
  • Cognition / drug effects*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / enzymology
  • Cognitive Dysfunction / prevention & control*
  • Cognitive Dysfunction / psychology
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Galactosamine
  • Maze Learning / drug effects
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Nootropic Agents / isolation & purification
  • Nootropic Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Sapindaceae* / chemistry
  • Signal Transduction
  • ras Proteins / metabolism*

Substances

  • Nootropic Agents
  • Plant Extracts
  • Aluminum Chloride
  • Galactosamine
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins

Supplementary concepts

  • Dimocarpus