Neuroprotective Effects of 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside From Polygonum Multiflorum Against Glutamate-Induced Oxidative Toxicity in HT22 Cells

J Ethnopharmacol. 2017 Jan 4;195:64-70. doi: 10.1016/j.jep.2016.12.001. Epub 2016 Dec 7.


Ethnopharmacological relevance: Since ancient times, Polygonum multiflorum Thunb. has been used to treat premature grey hair, dizziness, and blurred vision in East Asia. A major bioactive constituent of this medicinal herb, 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside (THSG), has antioxidant activity and exerts beneficial effects on cognition and memory.

Aim of the study: The purpose of the current study was to determine if THSG affects hippocampal neuronal cell death and mitochondrial function following exposure to oxidative stress.

Materials and methods: HT22 hippocampal cells with or without THSG pretreatment were exposed to glutamate, and the effects on cell viability and expression of molecules related to apoptotic cell death were examined using biochemical techniques, flow cytometry, western immunoblotting, and real-time polymerase chain reaction.

Results: Pretreatment with THSG significantly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase as well as apoptotic cell death. THSG inhibited generation of reactive oxygen species (ROS), expression of heme oxygenase-1, and activation of caspase-3 and calpain-1 proteases, all of which were increased by glutamate. THSG inhibited glutamate-induced disruption of mitochondrial membrane potential (MMP) and voltage-dependent anion channel-1. It also regulated the ratio of Bax to Bcl-2.

Conclusions: These results indicate that THSG has a marked neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. These findings suggest the potential of THSG as a new therapeutic agent for the treatment of cognitive disorders.

Keywords: 2,3,5,4′-tetrahydoxystilbene-2-O-β-D-glucoside; Mitochondrial dysfunction; Neuroprotection; Oxidative stress; Polygonum multiflorum.

MeSH terms

  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fallopia multiflora / chemistry*
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Glutamic Acid / toxicity*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Reactive Oxygen Species / metabolism
  • Stilbenes / isolation & purification
  • Stilbenes / pharmacology*
  • Voltage-Dependent Anion Channel 1 / metabolism


  • 2',3',4',5'-tetrahydroxystilbene-2-O-beta-D-glucoside
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Glucosides
  • Neuroprotective Agents
  • Plant Extracts
  • Reactive Oxygen Species
  • Stilbenes
  • Vdac1 protein, mouse
  • Glutamic Acid
  • Voltage-Dependent Anion Channel 1