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.
Highlights
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy with platinum drugs, taxanes, Catharanthus roseus alkaloids, thalidomide, and bortezomib
It has been reported that the total incidence of CIPN is more than 60%, while for oxaliplatin and taxanes, rates may be as high as 90% [1]. e occurrence of CIPN is dose dependent and may be relieved by dose reduction or drug withdrawal. e emergence of CIPN seriously affects the efficacy of chemotherapy and the quality of life of patients [2]
Network pharmacology is based on the similarity of the structure and efficacy of drugs to construct a drug-target network to explore the mechanisms of action of different agents
Summary
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy with platinum drugs, taxanes, Catharanthus roseus alkaloids, thalidomide, and bortezomib. Chamber written by Zhang Zhongjing, a medical scientist in the Han Dynasty (25 AD), and represents one of the more commonly used clinical herbal formulations It consists of five herbs: Hedysarum Multijugum Maxim (Huang Qi), Cinnamomi Ramulus (Gui Zhi), Paeoniae Radix Alba (Bai. Fructus (Da Zao). We have confirmed the efficacy of HQGZWWD in the prevention and treatment of CIPN without reducing antitumor activity of chemotherapeutic drugs in the animal model and cancer patients [9]. Network pharmacology is based on the similarity of the structure and efficacy of drugs to construct a drug-target network to explore the mechanisms of action of different agents It emphasizes the multichannel regulation of signaling pathways to improve the therapeutic effects of drugs and to reduce their toxicity and adverse effects, so as to improve the success rate of new drug clinical trials and save on the costs involved in drug research. It has been widely used to explore the therapeutic mechanisms of TCM in diseases involving the cardiovascular and nervous systems, respiratory diseases, diabetes, cancer, and osteoarthropathy and has achieved significant results [11,12,13,14,15,16]. e purpose of this study was to analyze the pathogenesis of CIPN and the potential therapeutic mechanisms of HQGZWWD through network pharmacology, so as to provide a theoretical basis for the clinical application of herbal formulations
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