Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats

J Pharm Pharmacol. 2020 Nov;72(11):1629-1644. doi: 10.1111/jphp.13345. Epub 2020 Aug 2.

Abstract

Objectives: Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect.

Methods: In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and α-mangostin (α-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats.

Key findings: HPLC analysis revealed that XEFGM contained 55.84% of α-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and α-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity.

Conclusions: However, α-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. α-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by α-MG. In conclusion, α-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, α-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

Keywords: Garcinia mangostana; chronic cerebral hypoperfusion; cognitive; xanthone; α-mangostin.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cerebrovascular Circulation
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / metabolism
  • Cerebrovascular Disorders / physiopathology
  • Cerebrovascular Disorders / psychology
  • Chronic Disease
  • Cognition / drug effects
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / psychology
  • Disease Models, Animal
  • Garcinia mangostana* / chemistry
  • Male
  • Memory / drug effects*
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats, Sprague-Dawley
  • Spatial Learning / drug effects*
  • Xanthones / isolation & purification
  • Xanthones / pharmacology*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Plant Extracts
  • Xanthones
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • mangostin