{"title":"Evaluation of anti-hyperuricemic and nephroprotective activities and discovery of new XOD inhibitors of Morus alba L. root bark.","authors":"Yan-Ao Wang, Xu Guo, Meng-Qi Zhang, Shu-Tao Sun, Qi-Dong Ren, Mu-Xuan Wang, Li-Na Wang, Mohamed A Farag, Jin-Yue Sun, Chao Liu, Ying-Ying Chen","doi":"10.1016/j.jep.2025.119476","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>As a traditional Chinese medicine, Morus alba L. root bark (MAR) has diuretic and detumescent effects, which is used in prescriptions like Niaoduqing granules for hyperuricemia treatment. However, the anti-hyperuricemic and nephroprotective activities, underlying mechanism and material basis of MAR have not been reported.</p><p><strong>Aim of the study: </strong>This research aimed to explore the anti-hyperuricemic and nephroprotective activity and mechanism of MAR, along with the pursuit of potential xanthine oxidase (XOD) inhibitors within MAR.</p><p><strong>Materials and methods: </strong>XOD inhibitory assay and hyperuricemic mice model were employed to screen and estimate the active fraction of MAR. Then, active compositions were isolated and elucidated by diverse separation and spectroscopic techniques. The enzyme inhibition mechanism of the active compositions was investigated by enzyme kinetic and molecular docking.</p><p><strong>Results: </strong>The ethyl acetate fraction (MAR-EA) showed the strongest inhibitory activity against XOD. In hyperuricemic mice, MAR-EA decreased serum uric acid levels by suppressing XOD activity and modulating renal uric acid transporters (URAT1, GLUT9, ABCG2). Moreover, it alleviated hyperuricemia-induced kidney damage, which may be related to inhibiting the production of inflammatory factors. Noticeably, the combination of MAR-EA with allopurinol showed a synergistic effect. Meanwhile, a Diels-Alder adduct, albanol A (1) was isolated from MAR-EA with excellent XOD inhibition activity (IC<sub>50</sub> = 0.116 mg/mL), which was categorized as a mixed-type XOD inhibitor. The molecular docking outcomes demonstrated that albanol A (1) exhibited a desirable interaction with XOD.</p><p><strong>Conclusion: </strong>This research supports MAR and albanol A as anti-hyperuricemic drug candidates, laying a foundation for further exploration.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119476"},"PeriodicalIF":4.8000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.119476","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: As a traditional Chinese medicine, Morus alba L. root bark (MAR) has diuretic and detumescent effects, which is used in prescriptions like Niaoduqing granules for hyperuricemia treatment. However, the anti-hyperuricemic and nephroprotective activities, underlying mechanism and material basis of MAR have not been reported.
Aim of the study: This research aimed to explore the anti-hyperuricemic and nephroprotective activity and mechanism of MAR, along with the pursuit of potential xanthine oxidase (XOD) inhibitors within MAR.
Materials and methods: XOD inhibitory assay and hyperuricemic mice model were employed to screen and estimate the active fraction of MAR. Then, active compositions were isolated and elucidated by diverse separation and spectroscopic techniques. The enzyme inhibition mechanism of the active compositions was investigated by enzyme kinetic and molecular docking.
Results: The ethyl acetate fraction (MAR-EA) showed the strongest inhibitory activity against XOD. In hyperuricemic mice, MAR-EA decreased serum uric acid levels by suppressing XOD activity and modulating renal uric acid transporters (URAT1, GLUT9, ABCG2). Moreover, it alleviated hyperuricemia-induced kidney damage, which may be related to inhibiting the production of inflammatory factors. Noticeably, the combination of MAR-EA with allopurinol showed a synergistic effect. Meanwhile, a Diels-Alder adduct, albanol A (1) was isolated from MAR-EA with excellent XOD inhibition activity (IC50 = 0.116 mg/mL), which was categorized as a mixed-type XOD inhibitor. The molecular docking outcomes demonstrated that albanol A (1) exhibited a desirable interaction with XOD.
Conclusion: This research supports MAR and albanol A as anti-hyperuricemic drug candidates, laying a foundation for further exploration.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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