To Explore the Mechanism of Hawthorn in the Intervention of Hyperlipidemia Based on the Gene Expression Omnibus and Network Pharmacology

Abstract

A common clinical treatment for hyperlipidemia in China is hawthorn, a traditional Chinese herb. However, few researches have been done on its active ingredients and their possible mechanisms for treating hyperlipidemia. The active chemical constituents of hawthorn were obtained from the encyclopedia of traditional Chinese medicine, the bioavailability and druglikeness properties of each active ingredient of hawthorn were analyzed using SwissADME and their possible targets of action were predicted using SwissTargetPrediction and PharmMapper. Then, we used the Gene Expression Omnibus-related gene microarray data to mine the differentially expressed genes for hyperlipidemia. Meanwhile, we collected relevant targets of hyperlipidemia through the DrugBank, Online Mendelian Inheritance in Man, GeneCards, DisGeNET and Therapeutic Target Database. Based on this data, a component-target-disease pathway and a protein-protein interaction networks were constructed using search tool for the retrieval of interacting genes/proteins. Finally, Metascape was systematically used to analyze the targets of hawthorn intervention in hyperlipidemia. A total of 8 active components and 312 hawthorn targets were gathered and 343 prospective targets associated with hyperlipidemia were predicted, 25 of which shared targets with hawthorn-related targets. Gene ontology enrichment analysis revealed that the mechanism of action of hawthorn in intervention of hyperlipidemia lies in the regulation of lipid metabolism, nutrition level, hormone level and cholesterol transport process. The Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the peroxisome proliferator activated receptor signaling pathway contained the majority of the core targets. Molecular docking verified that hawthorn could bind closely to the core targets. According to the findings of network pharmacology and enrichment analysis, we predicted that the main active components of hawthorn to intervene in hyperlipidemia are epicatechin, officinalic acid and quercetin, which mainly intervene in hyperlipidemia through the peroxisome proliferator activated receptor signaling pathway.