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Meta-Analysis
. 2020 Dec;58(1):932-943.
doi: 10.1080/13880209.2020.1817103.

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

Pengji Yi  1 , Zheyu Zhang  1   2 , Siqi Huang  1 , Jiahua Huang  3 , Weijun Peng  1 , Jingjing Yang  4   5
Affiliations
Free PMC article
Meta-Analysis

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

Pengji Yi et al. Pharm Biol. 2020 Dec.
Free PMC article

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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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Flow diagram of the search process.
Figure 2.
Figure 2.
Forest plot showed the effect of KXS therapies on outcomes of the water maze.
Figure 3.
Figure 3.
Compound-target of the treating AD network.
Figure 4.
Figure 4.
Protein–protein interaction network of treating AD.
Figure 5.
Figure 5.
GO enrichment analysis of treating AD targets.
Figure 6.
Figure 6.
KEGG enrichment analysis of treating AD targets.
Figure 7.
Figure 7.
Compound–target–pathway of treating AD network.
Figure 8.
Figure 8.
The docking model of compounds with ACHE.
Figure 9.
Figure 9.
The docking model of compounds with ADRA2A.
Figure 10.
Figure 10.
The docking model of compounds with CHRM2.
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Publication types

Grants and funding

This work was financially supported by the National Natural Science Foundation of China [No. 81873169, 81603670] and Hunan Provincial Natural Science Foundation of China (No. 2017JJ3459, 2020JJ4803).