The ameliorating effects of 2,3-dihydroxy-4-methoxyacetophenone on scopolamine-induced memory impairment in mice and its neuroprotective activity

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6732-6. doi: 10.1016/j.bmcl.2013.10.032. Epub 2013 Oct 28.

Abstract

We isolated 2,3-dihydroxy-4-methoxyacetophenone, a neuroprotective compound from Cynenchum paniculatum in our previous study. The present study was conducted to investigate the possible neuroprotective effect of 2,3-dihydroxy-4-methoxyacetophenone that has been previously isolated from Cynenchum paniculatum on hippocampal neuronal cell line, HT22 cells and its possible cognitive-enhancing effect on scopolamine-induced amnesia in mice. Neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells was evaluated by MTT assay. Also, cognitive enhancing effect against scopolamine (1mg/kg, ip) induced learning and memory deficit was measured by Morris water maze test. Oral administered of 2,3-dihydroxy-4-methoxyacetophenone (1, 10, 20, 40 and 50mg/kg) to amnesic mice induced by scopolamine. In Morris water maze test, 2,3-dihydroxy-4-methoxyacetophenone (50mg/kg) improved the impairment of spatial memory induced by scopolamine. 2,3-Dihydroxy-4-methoxyacetophenone protect HT22 cells on glutamate induced cell-death in a dose-dependent manner (EC50 value: 10.94μM). Furthermore, 2,3-dihydroxy-4-methoxyacetophenone was found to inhibit [Ca(2+)] accumulation in HT22 cells and had antioxidantive activity. The results showed that 2,3-dihydroxy-4-methoxyacetophenone exert neuroprotective and cognitive-enhancing activities through its antioxidant activity. We suggest that 2,3-dihydroxy-4-methoxyacetophenone improves cognitive function and may be helpful for the treatment of Alzheimer's disease.

Keywords: 2,3-Dihydroxy-4-methoxyacetophenone; Cognitive enchancing effect; Neuroprotective effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / chemistry
  • Acetophenones / isolation & purification
  • Acetophenones / pharmacology*
  • Acetophenones / therapeutic use
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Apocynaceae / chemistry
  • Apocynaceae / metabolism
  • Apoptosis / drug effects*
  • Avoidance Learning / drug effects*
  • Calcium / metabolism
  • Cell Line
  • Glutamic Acid / chemistry
  • Glutamic Acid / toxicity
  • Guaiacol / analogs & derivatives*
  • Guaiacol / chemistry
  • Guaiacol / isolation & purification
  • Guaiacol / pharmacology
  • Guaiacol / therapeutic use
  • Memory Disorders / chemically induced*
  • Memory Disorders / drug therapy
  • Mice
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Scopolamine*

Substances

  • 2,3-dihydroxy-4-methoxyacetophenone
  • Acetophenones
  • Antioxidants
  • Neuroprotective Agents
  • Glutamic Acid
  • Guaiacol
  • Scopolamine
  • Calcium