ABSTRACT
This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.
Subject(s)
Humans , Chemical and Drug Induced Liver Injury, Chronic , Drugs, Chinese Herbal/pharmacology , Glycyrrhiza , Medicine, Chinese Traditional , Network PharmacologyABSTRACT
Objective::To explore the potential active ingredients and possible anti-breast cancer mechanism of Glycyrrhizae Radix et Rhizome and Aurantii Fructus based on the method of network pharmacology. Method::The main potential targets of Glycyrrhizae Radix et Rhizome and Aurantii Fructus on breast cancer were summarized by comparing the Glycyrrhizae Radix et Rhizome-Aurantii Fructus active ingredients screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and breast cancer targets searched in Therapeutic Target Database (TTD). Cytoscape 3.7.1 software was used to establish a Glycyrrhizae Radix et Rhizome-Aurantii Fructus active ingredients-target-disease network and perform topology analysis based on the network. Result::According to related conditions of drug-like (DL) and oral bioavailability (OB), the network of Glycyrrhizae Radix et Rhizome-Aurantii Fructus active ingredients-breast cancer target was obtained, covering a total of 133 nodes, 116 chemical components and 17 breast cancer drug targets, 109 active components of Glycyrrhizae Radix et Rhizome interacting with breast cancer drug target, 6 active ingredients of Aurantii Fructus interacting with breast cancer drug targets, and 1 common active ingredient of Aurantii Fructus and Glycyrrhizae Radix et Rhizome interacting with breast cancer targets. There were 400 breast cancer target-interaction target pairs in the network diagram. Conclusion::The anti-breast cancer effect of Glycyrrhizae Radix et Rhizome and Aurantii Fructus is based on the overall pharmacodynamic effect of multi-component, multi-pathway and multi-target, the investigation of its potential anti-breast cancer mechanism provides theoretical basis for further experimental research.