Abstract

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

Highlights

  • Gastric cancer is the fifth common malignancy in the world and continues to be the most prevalent cancer in Eastern Asia, especially China [1]

  • gastric precancerous lesions (GPL) is related to the development of gastric cancer that progressively advances through the formation of sequential lesions, and the treatment of precancerous lesions offers an effective measure for decreasing morbidity in the initial phase of gastric carcinogenesis

  • We employed a systems pharmacology approach by integrating active compound screening, target prediction, network analysis, and pathway analysis to explore the molecular mechanisms underlying the therapeutic effect of the Wei Pi Xiao (WPX) decoction in the treatment of GPL

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Summary

Introduction

Gastric cancer is the fifth common malignancy in the world and continues to be the most prevalent cancer in Eastern Asia, especially China [1]. Several therapeutic strategies have been developed for the treatment of gastric carcinoma over the years, the long-term survival rate is low [2]. It is essential to explore novel molecular targets for the treatment of gastric carcinoma. Gastric carcinogenesis is a multistep and continuous process arising from nonatrophic gastritis, which proceeds to atrophic gastritis, metaplasia, and dysplasia and to adenocarcinoma [3]. The high mortality rate of patients with gastric cancer can be reduced by the early detection of precancerous lesions [4]. The early intervention of gastric precancerous lesions (GPL), which primarily comprise intestinal metaplasia and dysplasia [5], is an effective strategy for preventing the development of gastric cancer

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