Integrated meta-analysis, network pharmacology, and molecular docking to investigate the efficacy and potential pharmacological mechanism of Kai-Xin-San on Alzheimer's disease

  • Pharm Biol. 2020 Dec;58(1):932-943. doi: 10.1080/13880209.2020.1817103.
Pengji Yi  1 ,  Zheyu Zhang  1  2 ,  Siqi Huang  1 ,  Jiahua Huang  3 ,  Weijun Peng  1 ,  Jingjing Yang  4  5
Affiliations
  • 1. Department of Integrated Traditional Chinese and Western Medicine, the Second Xiangya Hospital, Central South University, Changsha, China.
  • 2. Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China.
  • 3. Hunan Academy of Chinese Medicine, Changsha, China.
  • 4. Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, China.
  • 5. Xiangya Nursing School, Central South University, Changsha, China.
PMID: 32956608 DOI: 10.1080/13880209.2020.1817103
Abstract

Context: Kai-Xin-San (KXS) has been used to treat Alzheimer's disease (AD) for thousands of years. However, no quantitative data regarding AD treatment using KXS are available. Moreover, its active compounds and mechanism of action for the treatment of AD remain largely unclear.

Objectives: To evaluate the efficacy and the potential pharmacological mechanisms of KXS in AD treatment.

Materials and methods: A systematic collection of KXS experiments was conducted from PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang Data up to February, 2020. Review Manager 5 software was used for meta-analysis. In network pharmacology, components of KXS were screened, AD-related genes were then identified and the 'component-target-pathway' network constructed. Molecular docking was finally employed for in silico simulation matching between representative KXS compounds and their target genes.

Results: Meta-analysis revealed that KXS improves the cognitive benefits in AD models by reducing the time of escape latency (SMD = -16.84) as well as increasing the number of cross-platform (SMD = 2.56) and proportion of time in the target quadrant (SMD = 7.52). Network pharmacology identified 25 KXS active compounds and 44 genes targets. DRD2, MAOA, AChE, ADRA2A and CHRM2 were core target proteins. Besides, 22 potential pathways of KXS were identified, like cholinergic synapses, the cGMP/PKG pathway and calcium signalling. Molecular docking showed that stigmasterol, aposcopolamine and inermin can closely bind three targets (AChE, ADRA2A and CHRM2).

Discussion and conclusion: These findings suggest that KXS exerts effect on AD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of KXS.

Keywords
Traditional Chinese medicine formula; dementia; molecular docking technology; pharmacological network.
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