Polysaccharide of Taxus chinensis var. mairei Cheng et L.K.Fu attenuates neurotoxicity and cognitive dysfunction in mice with Alzheimer's disease

Pharm Biol. 2020 Dec;58(1):959-968. doi: 10.1080/13880209.2020.1817102.

Abstract

Context: Polysaccharide of Taxus chinensis var. mairei Cheng et L.K.Fu (Taxaceae) (PTM) functions in anti-apoptosis and antioxidation, but its function on Alzheimer's disease (AD) remains unclear.

Objective: To investigate the effect of PTM on AD.

Materials and methods: C57BL/6J mice were randomly divided into three groups: control, d-galactose (d-gal), and d-gal + PTM. AD-like symptom was induced by d-gal for 6 weeks, followed with PTM (0.4 g/kg/d) for 14 days. PTM was added to BV2 cells stimulated with d-gal (1, 10, 20, 50, 100 and 500 μg/mL). Cell viability was evaluated by MTT assay. The expression of NRF2, SOD, cleaved caspase-3, Bax and Bcl-2 were detected with Western blot analysis. Cognitive function was evaluated by Morris water maze test.

Results: Decreased cleaved caspase-3 (1.30 ± 0.09) and Bax/Bcl2 ratio (1.32 ± 0.11) were observed in BV2 cells induced by d-gal + PTM (50 μg/mL). Increased MDA and ROS and decreased SOD were observed in d-gal group. However, decreased MDA (175 ± 9 ng/mL) and ROS level (188 ± 38 ng/mL) were observed after treated with PTM group (p < 0.05). In addition, the expression of NRF2 decreased in d-gal group (0.75 ± 0.09) but increased after treated with PTM (p < 0.05). Furthermore, decreased Aβ1-42 was observed and the cognitive function was improved after PTM intervention (p < 0.05).

Conclusions: This is the first report that PTM inhibited oxidative stress and apoptosis in AD. The result will further accelerate the applications of Taxus chinensis var. mairei and the treatment for AD.

Keywords: Oxidative stress; apoptosis; spatial learning ability.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Galactose
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Polysaccharides / administration & dosage
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Taxus / chemistry*

Substances

  • Polysaccharides
  • Galactose

Grants and funding

This work was supported by Taizhou Science and Technology Plan Project of Zhejiang Province [No. 15yw02 and 1701KY27].