Effect of Eucommia ulmoides leaves on hyperuricemia and kidney injury induced by a high-fat/high-fructose diet in rats

• Published in: Iranian journal of basic medical sciences Vol. 25; no. 4; pp. 527 - 535
• Main Authors: Gong, Man, Zhang, Hong, Liu, Xiaoqian, Li, Qingxia, Zhang, Yang, Zhang, Weijin, Huang, Na, Chen, Anying, Dai, Liping, Wang, Zhimin
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01-04-2022
• Subjects: eucommia ulmoides leaves; Flavonoids; high-fat and high-fructose diet; hyperuricemia; Inflammation; kidney injury; Leaves; Metabolism; molecular docking; network pharmacology; Original; Tumor necrosis factor-TNF; Uric acid; Hyperuricemia; Network pharmacology; High-fat and high-fructose diet; Kidney injury; Eucommia ulmoides leaves; Molecular docking
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/ijbms.2022.62681.13867

To investigate the protective and preventive treatment effects of
leaves on a rat model of high-fat and high-fructose diet (HFFD) induced hyperuricemia and renal injury.
Network pharmacology and molecular-docking methods were used to predict the effects and action mechanisms of the major components of
leaves on hyperuricemia. Combining literature collection, we used SciFinder and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform to collect
leaf flavonoid and iridoid components. Swiss Target Prediction, Similarity ensemble approach (SEA), GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database were used to obtain core targets, and the Search Tool for Recurring Instances of Neighbouring Genes (STRING) protein database was used as core target for gene ontology enrichment Set and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was applied to predict the pathways regulating the metabolism of uric acid. The selected targets and targeting efficacy were validated using a rat model of hyperuricemia and renal injury induced by a high-fat and high-fructose diet.
A total of 32 chemical components with effective targets, which regulated the PI3K-AKT pathway and endocrine resistance, were collected. Molecular docking results showed that iridoids and flavonoids are bound to proteins related to inflammation and uric acid metabolism. In addition, it was verified via animal experiments that an
leaf extract ameliorated hyperuricemia, renal injury, and inflammation, which are closely related to the targets Interleukin- 6 (IL-6), Tumor necrosis factor-α (TNF-α), Toll-Like Receptor 4 (TLR4), and Glucose transporter 9 (GLUT9).
leaf flavonoids and iridoids ameliorate hyperuricemia and uric-acid-induced inflammation through a multi-component, multi-target, and multi-pathway mechanism, which provides a theoretical basis for the development of therapeutics from
leaf components.