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. 2020 Jun 25:2020:6317230.
doi: 10.1155/2020/6317230. eCollection 2020.

Enhancing and Complementary Mechanisms of Synergistic Action of Acori Tatarinowii Rhizoma and Codonopsis Radix for Alzheimer's Disease Based on Systems Pharmacology

Shengwei Liu  1   2 , Cui He  1 , Yuan Liao  3 , Hailin Liu  2   4 , Wanli Mao  5 , Zhengze Shen  1
Affiliations

Enhancing and Complementary Mechanisms of Synergistic Action of Acori Tatarinowii Rhizoma and Codonopsis Radix for Alzheimer's Disease Based on Systems Pharmacology

Shengwei Liu et al. Evid Based Complement Alternat Med. .

Abstract

Materials and methods: In this study, a systems pharmacology-based strategy was used to elucidate the synergistic mechanism of Acori Tatarinowii Rhizoma and Codonopsis Radix for the treatment of AD. This novel systems pharmacology model consisted of component information, pharmacokinetic analysis, and pharmacological data. Additionally, the related pathways were compressed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the organ distributions were determined in the BioGPS bank.

Results: Sixty-eight active ingredients with suitable pharmacokinetic profiles and biological activities were selected through ADME screening in silico. Based on 62 AD-related targets, such as APP, CHRM1, and PTGS1, systematic analysis showed that these two herbs were mainly involved in the PI3K-Akt signaling pathway, MAPK signaling pathway, neuroactive ligand-receptor interaction, and fluid shear stress and atherosclerosis, indicating that they had a synergistic effect on AD. However, ATR acted on the KDR gene, while CR acted on IGF1R, MET, IL1B, and CHUK, showing that they also had complementary effects on AD. The ingredient contribution score involved 29 ingredients contributing 90.14% of the total contribution score of this formula for AD treatment, which emphasized that the effective therapeutic effects of these herbs for AD were derived from both ATR and CR, not a single herb. Organ distribution showed that the targets of the active ingredients were mainly located in the whole blood, the brain, and the muscle, which are associated with AD.

Conclusions: In sum, our findings suggest that the systems pharmacology methods successfully revealed the synergistic and complementary mechanisms of ATR and CR for the treatment of AD.

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Conflict of interest statement

The authors declare that they have no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
The complete framework of the systems pharmacology approach.
Figure 2
Figure 2
The molecular variation of all ingredients in ATR and CR. ∗P < 0.01 by two tailed t-test (vs. CR).
Figure 3
Figure 3
GO enrichment analysis of the targets of ATR and CR.
Figure 4
Figure 4
Component-target network of ATR and CR. The orange and yellow rhombus nodes are the active ingredients of ATR and CR, and the pink and light blue ellipse nodes are related targets. The blue rhombus nodes are the shared active ingredients HMF (DS75) and apigenin (DS77). The green ellipse nodes are the shared targets of ATR and CR.
Figure 5
Figure 5
Target-pathway networks of ATR and CR. The green nodes are the targets of ATR and CR, while the orange nodes represent the pathways.
Figure 6
Figure 6
Distribution of partial targets of ATR and CR on the compressed pathway.
Figure 7
Figure 7
CS and accumulative CS of active ingredients in ATR and CR.
Figure 8
Figure 8
Compound-target-organ networks of ATR and CR.
See this image and copyright information in PMC

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