Rhizophora mucronata attenuates beta-amyloid induced cognitive dysfunction, oxidative stress and cholinergic deficit in Alzheimer's disease animal model

Metab Brain Dis. 2016 Aug;31(4):937-49. doi: 10.1007/s11011-016-9831-0. Epub 2016 May 17.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by accumulation and deposition of Aβ peptide in human brain. The present study aimed to determine the protective effect of catechin rich extract of MERM (methanolic extract of Rhizophora mucronata) on Aβ (25-35) induced cognitive impairment and neuronal toxicity in mice. In the present study AD characteristics were induced by intracerberoventricular administration of aggregated Aβ (25-35) in the Swiss albino mice. Learning and memory deficits were assessed using behavioral assays such as Morris water maze, Y-maze and step down avoidance tasks. Oxidative stress mediated impairment were assessed by measuring the activities of enzymatic and non-enzymatic antioxidants, level of apoptotic protein and oxidative markers in the hippocampus and frontal cortex region. Histolopathological analysis of brain was also carried out. Results illustrated that oral treatment of MERM (200 and 400 mg/kg bw) significantly attenuated Aβ (25-35) induced memory impairment as evaluated by behavioral tests. In addition treatment with MERM attenuated the elevation of β-secretase activity accompanying the reduced level of Aβ (25-35) in the cortex and hippocampus of brain. MERM also enhanced the cognitive function by significantly inhibiting AChE, BuChE and MAO-B. Furthermore, MERM attenuated lipid peroxidation, protein oxidation, restored the antioxidant status and inhibited neuronal apoptosis by down-regulating the level of caspase 3 and Bax protein. These data suggest that MERM rich in catechin can act as promising drug for AD treatment because of its antioxidant, anti-apoptotic and reducing Aβ oligomer activities.

Keywords: Apoptosis; Aβ (25–35); Cognitive impairment; Oxidative stress; Rhizophora mucronata; β-secretase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides
  • Animals
  • Apoptosis / drug effects*
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Lipid Peroxidation / drug effects
  • Maze Learning / drug effects
  • Mice
  • Monoamine Oxidase / metabolism
  • Oxidative Stress / drug effects*
  • Peptide Fragments
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rhizophoraceae
  • Superoxide Dismutase / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Plant Extracts
  • bcl-2-Associated X Protein
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Monoamine Oxidase
  • Glutathione Reductase
  • Acetylcholinesterase
  • Amyloid Precursor Protein Secretases
  • Caspase 3