Effect of tanshinone on the levels of nitric oxide synthase and acetylcholinesterase in the brain of Alzheimer's disease rat model

Clin Invest Med. 2008 Oct 1;31(5):E248-57. doi: 10.25011/cim.v31i5.4871.

Abstract

Purpose: To determine the influence of tanshinone on the levels of nitric oxide synthase (NOS) and acetylcholinesterase (AChE) in the brain of an Alzheimer's Disease (AD) rat model and on its potential therapeutic mechanism.

Methods: 100 Male Sprague Dawley rats were divided into three groups: control group, model group and tanshinone treatment group. 10 microg A beta 1-42 was injected bilaterally into the dorsal lateral region of the dentate gyrus in the hippocampus of rats in the model and tanshinone treatment groups to prepare the AD models. 24h after modeling, tanshinone, 50mg/kg, was administered by gastric perfusion to rats in the tanshinone treatment group. Later, immunohistochemical assay and Western blot analysis were used to detect expression of neuronal NOS (nNOS) and inducible NOS (iNOS) in the rat hippocampus. Activity of AChE in each subregion (CA1 approximately CA4) of rats' hippocampus was determined by a histochemical technique.

Results: Expression of nNOS in the model group was down-regulated whereas iNOS was up-regulated. After A beta 1-42 injection, the number of AChE positive fibers in each subregion (CA1 approximately CA4) of the hippocampus was decreased compared with controls. With tanshinone administration, the changes were improved to varying degrees.

Conclusion: Tanshinone modulates AChE and NOS proteins concentrations in the hippocampus of AD rats. This may have therapeutic potential in AD rats.

MeSH terms

  • Abietanes
  • Acetylcholinesterase / biosynthesis*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology*
  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Hippocampus / enzymology*
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Nitric Oxide Synthase Type I / biosynthesis*
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Phenanthrenes / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Abietanes
  • Immunosuppressive Agents
  • Phenanthrenes
  • tanshinone
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Acetylcholinesterase