Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-β/NF-κb signaling pathway: Network pharmacology and experimental validation

Ethnopharmacological relevance: Qinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. Aim of the study: This study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. Materials and methods: The components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. Results: We identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-alpha, TRAF2, IKKB-beta, and NF-kappa B proteins in the liver of hyperlipidemic rats. Conclusion: QLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-alpha/IKKB-beta/NF-kappa B signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.