Mechanistic Prediction of Chinese Herb Compound (Zhi Zhu Ma Ren Pill) in the Treatment of Constipation Using Network Pharmacology and Molecular Docking

Abstract

Background: Constipation is one of the most prevalent chronic gastrointestinal diseases. Notably, previous studies have demonstrated that Chinese herbal compounds may exert effects on constipation. The present study aimed to predict the mechanisms underlying the effects of Zhi Zhu Ma Ren Pill (ZZMRP), which includes Aurantii Fructus Immaturus, Atractylodis Macrocephalae Rhizoma, Fructus Cannabis, Paeonia lactiflora and Radix Asteris in the treatment of constipation, using network pharmacology and molecular docking. Methods: The components and target information of ZZMRP were accessed using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform, and the associated targets of constipation were obtained from the GeneCards, Disgenet, Online Mendelian Inheritance in Man, DrugBANK and Therapeutic Target Database databases. The major targets were subsequently selected using a Venn diagram and network topology analysis, which was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to authenticate the binding activity between active components and core targets. Results: A total of 44 active components, 249 targets of ZZMRP and 1501 targets associated with constipation were acquired. A total of 122 intersection targets were discovered between ZZMRP and constipation. Subsequently, 18 key targets were authenticated, including tumor protein 53, RAC-alpha serine/threonine-protein kinase, JUN and caspase-3. GO and KEGG pathway enrichment analysis indicated that mitogen-activated protein kinase, tumor necrosis factor, and phosphoinositide 3-kinase/protein kinase B signaling pathways may be involved in the treatment of constipation using ZZMRP. Molecular docking suggested that quercetin, kaempferol, and luteolin exhibited high binding affinities with several of the primary targets. Conclusions: The active components, core targets, and signaling pathways of ZZMRP in the treatment of constipation were predicted, which may be applicable to the development of treatments for constipation and application of ZZMRP.