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. 2020 Nov 22:2020:2363262.
doi: 10.1155/2020/2363262. eCollection 2020.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology

Jia-Lin Gu  1   2 , Guo-Li Wei  1   3 , Yu-Zhu Ma  1   2 , Jin-Zhi Zhang  1   2 , Yi Ji  1   2 , Ling-Chang Li  1   3 , Jia-Lin Yu  1   3 , Can-Hong Hu  1   3 , Jie-Ge Huo  1   3
Affiliations

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology

Jia-Lin Gu et al. Evid Based Complement Alternat Med. .

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

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Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
CIPN target protein-protein interaction network. Nodes with a darker color have a higher degree in the network.
Figure 2
Figure 2
Mcode clustering of CIPN targets in the protein-protein interaction network. (a–c) represent clusters 1, 2, and 3, respectively.
Figure 3
Figure 3
GO biological process analysis of CIPN clusters.
Figure 4
Figure 4
KEGG pathways of CIPN targets.
Figure 5
Figure 5
Herbs-compounds-targets network of HQGZWWD. Red triangle nodes represent herbs, diamond nodes represent compounds, green diamond nodes represent repeated compounds in herbs, peripheral nodes represent overlapping targets between HQGZWWD and CIPN, gray round nodes were not identified in the previously constructed CIPN targets network, and blue rounds represent targets derived from predictive data.
Figure 6
Figure 6
Overlapping targets network. The node having a darker color has a higher degree in the network.
Figure 7
Figure 7
(a) GO functional analysis of overlapping targets. (b) KEGG pathway enrichment analysis of overlapping targets.
See this image and copyright information in PMC

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