RESUMO
Objective: Using network pharmacology analysis method to explore the efficacy network and mechanism of Pediatric Xiaoji Zhike Oral Liquid (PXZOL) in treating children with food accumulation cough. Methods: We collected main components in PXZOL and their targets by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID) combined with literature. Functional constipation related targets were searched from Comparative Toxicogenomics Database (CTD), PubMed, Drugbank, and other databases combined with literature. The herb-component-target network and ingredient-target-disease interaction Protein-protein interaction (PPI) network of PXZOL were constructed by Cytoscape 3.6.0 software. A core target network was constructed by screening targets in the PPI network. Gene Ontology (GO) analysis and Pathway analysis of the core target network were performed by using the ClueGO plugin. Organ localization of core targets was detected using the BioGPS database. Results: GO analysis showed that PXZOL exerted antitussive effect mainly by regulating nuclear transcription factor-κB (NF-κB) signaling. The role of depletion is mainly achieved by the synthesis and regulation of related proteins. Pathway results showed that PXZOL exerts antitussive effects mainly through mitogen-activated protein kinase (MAPK) signaling pathway, retinoic acid-inducible gene-I (RIG-I)-like receptor signaling pathway, interleukin 17 (IL-17) signaling pathway, and TNF receptor associated factor 6 (TRAF6)-mediated NF-κB activation. The role of elimination is mainly achieved through a variety of immune and inflammatory signaling pathways. In terms of organ localization, nearly 50% of target sites for antitussive targets, targets for elimination, and common targets have more expression in the lungs and large intestine. Conclusion: PXZOL is based on the theory of traditional Chinese medicine "lung and large intestine phase" and the prescription of latent medicine, modern pharmacology research showed that the effect of "resolving accumulation and relieving cough" mostly concentrated on immunity and inflammation, and network pharmacology research found that the target and its common target have nearly 50% more expression in the lungs and large intestine. From the infective disease and the network of action, we suggest that the efficacy of PXZOL is manifested by mucosal immunity and inflammation-mediated pathways. The scientific nature of the theory with the large intestine also lays the foundation for further in-depth research and verification of the model and clinical practice of pediatric food accumulation cough.
RESUMO
Objective: To investigate the function network and potential mechanisms of effects of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation by using network pharmacology methods. Methods: TCMSP, TCMID, and Swiss Target Prediction online prediction databases were used to screen the components and their potential targets of Chaihu Plus Mangxiao Decoction using oral availability (OB) and drug-like (DL) as the qualification conditions. PubMed, CTD, TTD, and DrugBank were used to search functional constipation-related targets. STRING and Cytoscape were used to make targets network visualization, screen the key components and core targets with high a degree of the node; Finally, relevant software was applied to analyze core targets and predict the mechanism. Results: A number of 206 total components of Chaihu Plus Mangxiao Decoction were screened, and there were 998 corresponding targets, which were contained 295 targets associated with functional constipation. According to the analysis, there were 64 key components and 30 core targets involving the Chaihu Plus Mangxiao Decoction-induced treatment of functional constipation. After enrichment analysis and KEGG pathway analysis of 30 core targets, it was found that SCN9A, CFTR, HTR2A, OPRD1, PTGS1, and FGFR1 were involved in regulating biological processes including opioid receptor activity, water balance of the organism, terpenoids and biological receptors and subsequent mediating the function of serotonin receptors, arachidonic acid metabolism, transcriptional regulation of MECP2, cytochrome P450, biogenic amine-binding receptors, PI3K the aberrant expression, tyrosine-protein kinase signaling pathway, and exogenous foreign body stimulation. These biological targets and molecular signaling pathways may play a therapeutic role in the treatment of functional constipation. Conclusion: The mechanism of effect of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation is characterized by multiple targets and pathways. Saponins, flavonoids, and sterols may be the material basis for core functions, and serotonin receptors, opioid receptors and chloride channel-regulated receptors may be key targets of Chaihu Plus Mangxiao Decoction.