Gualou Guizhi decoction reverses brain damage with cerebral ischemic stroke, multi-component directed multi-target to screen calcium-overload inhibitors using combination of molecular docking and protein-protein docking

J Enzyme Inhib Med Chem. 2018 Dec;33(1):115-125. doi: 10.1080/14756366.2017.1396457.

Abstract

Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats. GLGZD contains Trichosanthin and various small molecular that they are the potential active ingredients directed against NR2A, NR2B, FKBP12 and Calnodulin target proteins/enzyme have been screened by computer simulation. "Multicomponent systems" is capable to create pharmacological superposition effects. The Chinese medicine compound prescriptions could be considered as promising sources of candidates for discovery new agents.

Keywords: Gualou Guizhi decoction; calcium-overload; inhibitors screening; reverses brain damage.

MeSH terms

  • Administration, Oral
  • Animals
  • Brain Ischemia / drug therapy*
  • Calcium / metabolism*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Molecular Docking Simulation*
  • Protein Binding / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Small Molecule Libraries / administration & dosage
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Stroke / drug therapy*
  • Structure-Activity Relationship
  • Tacrolimus Binding Protein 1A / antagonists & inhibitors
  • Tacrolimus Binding Protein 1A / metabolism
  • Trichosanthin / administration & dosage
  • Trichosanthin / chemistry
  • Trichosanthin / pharmacology

Substances

  • Drugs, Chinese Herbal
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Small Molecule Libraries
  • guizhi decoction
  • Trichosanthin
  • Tacrolimus Binding Protein 1A
  • Calcium
  • N-methyl D-aspartate receptor subtype 2A

Grants and funding

The authors are grateful to projects support from Ministry of Science and Technology of the People’s Republic of China (14C26243501795) and from Fujian Provincial Department of Science & Technology (2013Y0047).