دورية أكاديمية

Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial β-glucuronidases from the Tibetan medicine Rhodiola crenulata.

التفاصيل البيبلوغرافية
العنوان: Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial β-glucuronidases from the Tibetan medicine Rhodiola crenulata.
المؤلفون: Chen L; State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Hou XD; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China., Zhu GH; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Huang J; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Pharmacology and Toxicology Division, Shanghai Institute of Food and Drug Control, Shanghai 201203, China., Guo ZB; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Zhang YN; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Sun JM; Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China., Ma LJ; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Zhang SD; State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China., Hou J; State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China; College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Electronic address: houjie@dmu.edu.cn., Ge GB; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: geguangbo@shutcm.edu.cn.
المصدر: International journal of biological macromolecules [Int J Biol Macromol] 2024 May; Vol. 267 (Pt 1), pp. 131150. Date of Electronic Publication: 2024 Mar 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: Guildford, Eng., IPC Science and Technology Press.
مواضيع طبية MeSH: Rhodiola*/chemistry , Molecular Docking Simulation* , Gastrointestinal Microbiome*/drug effects , Enzyme Inhibitors*/pharmacology , Enzyme Inhibitors*/chemistry, Animals ; Mice ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Medicine, Tibetan Traditional ; Kinetics ; Male
مستخلص: Gut microbial β-glucuronidases (gmβ-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmβ-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmβ-GUS enzymes. Subsequently, the anti-gmβ-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmβ-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmβ-GUS in a non-competitive manner, with the K i values ranging from 0.12 μM to 1.29 μM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmβ-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmβ-GUS activity in mice feces, with the IC 50 value of 1.24 μM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmβ-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmβ-GUS associated enterotoxicity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG); Broad-spectrum inhibition; Gut microbial β-glucuronidases (gmβ-GUS); Rhodiolae Crenulatae extract (RCE); gmβ-GUS-associated toxicity
المشرفين على المادة: 0 (Enzyme Inhibitors)
0 (Plant Extracts)
تواريخ الأحداث: Date Created: 20240331 Date Completed: 20240507 Latest Revision: 20240507
رمز التحديث: 20240507
DOI: 10.1016/j.ijbiomac.2024.131150
PMID: 38556236
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0003
DOI:10.1016/j.ijbiomac.2024.131150