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

Document Type : Original Article

Authors

1 Henan University of Chinese Medicine, Henan Zhengzhou 450046, China

2 Engineering Technology Research Center for Comprehensive Development and Utilization of Authentic Medicinal Materials from Henan, Henan Zhengzhou 450046, China

3 The Second Affiliated Hospital of Zhengzhou University, Henan Zhengzhou,450014, China

4 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

5 Henan Zhongjing Key Laboratory of Prescription, Henan Zhengzhou 450046, China

Abstract

Objective(s): To investigate the protective and preventive treatment effects of Eucommia ulmoides leaves on a rat model of high-fat and high-fructose diet (HFFD) induced hyperuricemia and renal injury.
Materials and Methods: Network pharmacology and molecular-docking methods were used to predict the effects and action mechanisms of the major components of E. ulmoides leaves on hyperuricemia. Combining literature collection, we used SciFinder and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform to collect E. ulmoides 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.
Results: 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 E. ulmoides 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). 
Conclusion: E. ulmoides 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 E. ulmoides leaf components.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 25, Issue 4
April 2022
Pages 527-535

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