Molecular Targets and Mechanisms of Poria cocos-Licorice Drug Pair for the Treatment of Henoch–Schönlein Purpura Nephritis Based on Network Pharmacology

Abstract

Background: The herbal Poria cocos-Liquorice drug pair (PLDP) possesses the ability to be a diuretic, stimulating the spleen and benefiting the kidney, which plays an important role in the treatment of Henoch–Schönlein purpura nephritis (HSPN). However, the mechanism of action is unknown. Objectives: Through the method of network pharmacology, this research sought to determine the mechanism of PLDP against HSPN. Materials and Methods: The screening of active ingredients in PLDP was conducted by Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases, while their targets were obtained from the TCMSP and Swiss Target Prediction (STP) databases. The genes of HSPN were searched by OMIM, DisGeNET, and GeneCards databases. Then, the common targets of active ingredients in PLDP and HSPN were mapped by Venn analysis. To get the main targets, the researchers utilized the STRING database to construct the protein–protein interaction (PPI) network of the common targets. Then, the function of gene ontology (GO) and the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the main targets were examined on the Metascape database to identify the molecular mechanism of PLDP against HSPN. The most relevant signaling pathways with HSPN screened from the top 20 pathways were defined as the key pathways. Finally, the “active ingredient-main target-key pathway” network was built in order to identify the core targets and key active ingredients of PLDP against HSPN. Results: There were 101 active ingredients and 360 targets for PLDP. One hundred and fifty-seven genes for HSPN and 35 common targets between PLDP and HSPN were identified. Through the “active ingredient-main target-key pathway” network, quercetin, kaempferol, polyporenic acid C, dehydrotumulosic acid, poricoic acid A, and naringenin were identified as key active ingredients; TNF, NOS3, RELA, AKT1, ICAM1, and IFNG were identified as core targets; and the key pathways include TNF signaling pathways, HIF-1 signaling pathways, and IL-17 signaling pathways. Conclusion: The research initially investigated the pathways, active ingredients, and targets involved in PLDP against HSPN. The mechanism appears to be linked to its immunomodulatory and anti-inflammatory properties, thus establishing a scientific foundation for further investigation.