Analysis of the Efficacy and Pharmacological Mechanisms of Action of Zhenren Yangzang Decoction on Ulcerative Colitis Using Meta-Analysis and Network Pharmacology.

Guosheng Xing,Yan Liu,Haibing Hua,Xinlin Wu,Hua Wang,Zhen Zhang,Mingxing Hou,Yufeng Zhang

doi:10.1155/2021/4512755

Abstract

Objective We analyzed the efficacy and pharmacological mechanisms of action of Zhen Ren Yang Zang decoction (ZRYZD) on ulcerative colitis (UC) using meta-analysis and network pharmacology. Methods The major databases were searched for randomized controlled trials of ZRYZD for the treatment of UC. Meta-analysis of the efficacy of ZRYZD on UC was conducted using RevMan software. Active compounds and target genes were acquired using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. UC-related genes were searched using the GeneCards database. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using RGUI. A compound-target network was constructed using Cytoscape software, and a protein-protein interaction network was constructed using the STRING database. Molecular docking simulations of the macromolecular protein targets and their corresponding ligand compounds were performed using the AutoDock tool and AutoDock Vina software. Results Meta-analysis revealed that the total effective rate and recovery rate of clinical efficacy were significantly higher in the experimental group than those of the control group. The screening identified 169 active compounds and 277 active target genes for ZRYZD. The 277 active target genes were compared with the 4,798 UC-related genes. This identified 187 active target genes of ZRYZD for UC that correlated with 138 active compounds. GO functional enrichment and KEGG pathway enrichment analyses were performed, and compound-target and protein-protein interaction networks were constructed. The key compounds and key target proteins were then selected. Finally, target protein binding with the corresponding compound was analyzed using molecular docking. Conclusion Our findings demonstrate the effectiveness and safety of ZRYZD for the treatment of UC and provide insight into the underlying pharmacological mechanisms of action. Furthermore, key compounds were identified, laying the foundation for future studies on ZRYZD for the treatment of UC.

Highlights

Ulcerative colitis (UC) is a common chronic intestinal disease of unknown etiology and is associated with multifactorial, multilevel, and nonspecific inflammation [1]. e clinical manifestations of UC include diarrhea, abdominal pain, and stool containing mucus, pus, and/or blood. e incidence of UC is 1.2–20.3 per 100,000 persons per year, and its prevalence is 7.6–246.0 per 100,000 per year [2].e lesions in UC involve the rectum and sigmoid colon, sometimes throughout the whole colon, mainly invading the colorectal mucosa and submucosa and showing phased and diffuse distribution, resulting in a propensity for relapse [3]
E inclusion criteria included the following: the study was designed as a randomized controlled trials (RCTs), the participants had a diagnosis of UC, Zhen Ren Yang Zang decoction (ZRYZD) was used in the experimental group, the control group used conventional therapy without Traditional Chinese medicine (TCM) therapy, and there were clear outcome indicators
According to TCM theory, UC belongs to the category of “dysentery” and is characterized by dampness and heat accumulation, qi and blood disorder, and visceral food accumulation. e disease location of UC is in the intestine, and kidney qi insufficiency, spleen deficiency, endogenous dampness, and heat are considered the primary causes of this disease

Summary

Introduction

Ulcerative colitis (UC) is a common chronic intestinal disease of unknown etiology and is associated with multifactorial, multilevel, and nonspecific inflammation [1]. e clinical manifestations of UC include diarrhea, abdominal pain, and stool containing mucus, pus, and/or blood. e incidence of UC is 1.2–20.3 per 100,000 persons per year, and its prevalence is 7.6–246.0 per 100,000 per year [2].e lesions in UC involve the rectum and sigmoid colon, sometimes throughout the whole colon, mainly invading the colorectal mucosa and submucosa and showing phased and diffuse distribution, resulting in a propensity for relapse [3]. Mesalazine, immunosuppressants, and corticosteroids are clinically used to treat UC; these drugs are needed chronically and can cause adverse reactions, and relapse is common after cessation [4, 5]. Traditional Chinese medicine (TCM) has a long history of treating diarrhea and dysentery and is compliant with the concept of individualized treatment [6]. Zhen Ren Yang Zang decoction (ZRYZD), first used during the Song Dynasty as the basic prescription for the treatment of diarrhea, primarily consists of yingsuke, roudoukou, hezi, rougui, dangshen, baizhu, danggui, baishao, muxiang, and gancao (scientific names: Pericarpium Papaveris (PP), Semen Myristicae (SM), Fructus Chebulae (FC), Cortex Cinnamomi (CC), Radix Codonopsis (RC), Rhizoma Atractylodis Macrocephalae (RAM), Radix Angelicae Sinensis (RAS), Radix Paeoniae Alba (RPA), Radix Aucklandiae (RA), and Radix Glycyrrhizae (RG), respectively) [10]. According to TCM theory, PP, SM, and FC are monarch and minister herbs and are regarded as the main components of ZRYZD

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Conclusion