Abstract
Eucommia ulmoides leaves have unique advantages in the treatment of metabolic diseases. In this study, 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 and Analysis Platform to collect E. ulmoides leaf flavonoid and iridoid components. Swiss Target Prediction, SEA, GeneCards, and the OMIM database were used to obtain core targets, and the STRING protein database was performed as core targets for gene ontology enrichment Set and 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. Isoquercetin, kaempferol, and quercetin were predicted via network pharmacology to have potential bioactivities and strong docking binding forces. 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 IL-6, TNF-α, TLR4, and GLUT9. In 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.
Facile fabrication of bio-based Eucommia Ulmoides rubber shape memory foams