Decoding Hippophae rhamnoides’ action of mechanism in Sjögren’s syndrome: A network pharmacology and molecular docking study

Abstract

This study aimed to decode the potential bioactive compounds and action mechanism of Hippophae rhamnoides in treating Sjögren’s syndrome using network pharmacology and molecular docking approach. The Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and HERB (a High--throughput Experiment- and Reference-guided database of TCM) database were used to identify the active components of -Hippophae rhamnoides and their targets. Databases, including GeneCards, Online Mendelian Inheritance (OMIM), and DisGeNET, were used to acquire the major targets of action in Sjögren’s syndrome. Venn diagrams were constructed to identify the compound gene targets. Then the Search Tool for the Retrieval of Interacting genes/proteins database (STRING) platform was used to build a protein–protein interaction (PPI) network to analyze the potential protein functional modules. Analysis of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed through the Metascape platform to predict their biological processes and decipher the mechanism of action. The drug component–target–action pathway network was constructed through the Cytoscape 3.8.2 software. Furthermore, the AutoDock Vina software was used to perform molecular docking of core components and key targets, validating binding affinity between potential core components and key targets. Twenty-two Hippophae rhamnoide candidate compounds and 208 potential targets for Sjögren’s syndrome were acquired. The network analysis showed that the core active ingredients of Hippophae rhamnoides in regulating Sjögren’s syndrome were quercetin, kaempferol, and beta-sitosterol (β-sitosterol). Core targets included albumin (ALB), epidermal growth factor receptor (EGFR), Caspase-3 (CASP3), peroxisome proliferator-activated receptor gamma (PPAR-gamma or PPARG), estrogen receptor (ER) ESR1, heat shock protein HSP 90-alpha, EC 3.6.4.10 (HSP90AA1), plasminogen, EC 3.4.21.7 (PLG), MAPK14, MAPK8, and MAPK1. The KEGG analyses demonstrated that Hippophae rhamnoides could exert their functioning against Sjögren’s syndrome by reacting with the lipid and atherosclerosis signaling pathway and tumor necrosis factor (TNF) signaling pathway. Further, molecular docking analysis suggested that 10 compounds of Hippophae rhamnoides could be effective to treat Sjögren’s syndrome by matching five core genes to docking pockets. This study indicated that Hippophae rhamnoides’ functioning effects on Sjögren’s syndrome could be attributed to the regulation of a network comprising multi-targets, multi-compounds, and multi-pathways.