Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer's Disease Based on Systems Biology

Oxid Med Cell Longev. 2019 Dec 31:2019:1707218. doi: 10.1155/2019/1707218. eCollection 2019.

Abstract

Kai-Xin-San (KXS), a classical Chinese traditional prescription, was widely applied in the treatment of Alzheimer's disease (AD), while its functional mechanisms still remain unclear. By using systems biology approaches at animal, cellular, and molecular levels, the improvement of KXS on cognitive impairment was achieved by inhibiting abnormal acetylcholinesterase. The function on the nerve skeleton was performed by regulating the Tau phosphorylation pathway. Its antioxidant, anti-inflammatory, and antiapoptotic effects by modulating the aberrant upregulation of ROS, proinflammatory factors, and apoptosis-related proteins in the brain were studied to reveal the synergistic therapeutic efficacy of KXS. Then, formula dismantling in vitro indicated that ginseng was the principal herb, whereas three other herbs served adjuvant roles to achieve the best effect. After that, the in vivo analysis of components into plasma and brain of AD rats showed that 8 of 23 components in blood and 4 of 10 components in brain were from ginseng, respectively, further verifying the principal status of ginseng and the synergistic effects of the formula. Thus, the anti-AD effects of KXS were achieved by multitargets and multichannels. The systems biology approaches presented here provide a novel way in traditional herbal medicine research.

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects
  • Brain / pathology
  • Cognition Disorders / complications
  • Cognition Disorders / drug therapy
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Inflammation / pathology
  • Male
  • Memory Disorders / complications
  • Memory Disorders / drug therapy
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Systems Biology*

Substances

  • Amyloid beta-Peptides
  • Drugs, Chinese Herbal
  • Kai-Xin-San