Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Gegen Qinlian Decoction for Rotavirus Enteritis

Abstract

Ethnopharmacological Relevance. Gegen Qinlian decoction (GGQLD) is an effective formula treatment for rotavirus enteritis (RVE), which has been applied for 1900 years. It consists of 4 herbal medicines corresponding to the four roles “monarch, minister, assistant, and guide,” which is the basic rule of prescription composition in traditional Chinese medicine (TCM). However, its active ingredients and therapeutic mechanism on RVE have not been fully investigated. Materials and Methods. In this study, a network pharmacology-based strategy was used to elucidate the mechanism of GGQLD for the treatment of RVE. Oral bioavailability and drug-likeness were taken as the judgment criteria to search the active ingredients of GGQLD in traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). The affinity between protein and ingredients was further determined using the similarity ensemble approach to find the corresponding targets. According to the genes related to enteritis in GeneCards database, the key targets were screened by intersections between drug and disease targets. And the therapeutic mechanism was predicted using the protein-protein interactions (PPIs), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which was verified by detecting calcium ion concentration with the fluorescent probe. Result. 130 active ingredients were screened from GGQLD, including (R)-canadine, moupinamide, formononetin, and other flavonoids. They act on a total of 366 targets, which is mainly distributed in the biological process of hormone binding or signaling pathways of neuroactive ligand receptor interaction, serotonergic synapse, and calcium signaling pathway. Furthermore, serotonin receptors, adrenergic receptors, cholinergic receptors, and dopamine receptors in the enteric nervous system may be the key targets of RVE treatment by GGQLD. Conclusion. This study demonstrated that the potential mechanism that GGQLD can effectively improve the symptoms of RVE may depend on the regulation of calcium ions, serotonin, and gastrointestinal hormone ion that could mutually affect the intestinal nervous system.