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Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota

文献类型：期刊论文

作者Zhu, Nanlin1; Duan, Haonan2; Feng, Yingying1; Xu, Wenwei1; Shen, Jianhua2; Wang, Kai2; Liu, Jia1,3
刊名EUROPEAN JOURNAL OF PHARMACOLOGY
出版日期2023-08-15
卷号953页码:12
ISSN号0014-2999
关键词Diabetic nephropathy Magnesium lithospermate B Gut microbiota Uremic toxins p -Cresyl sulfate metabolism
DOI10.1016/j.ejphar.2023.175812
通讯作者Wang, Kai(kwang@simm.ac.cn) ; Liu, Jia(jia.liu@simm.ac.cn)
英文摘要Diabetic nephropathy (DN) is a major cause of renal failure and urgently necessitates new therapeutic strategies. Magnesium lithospermate B (MLB) showed a good protective effect on kidney injure by oral administration, despite its extremely low bioavailability. The current study aimed to investigate its gut microbiota-targeted mechanism to explain the paradoxical properties of pharmacodynamics and pharmacokinetics. Here we show that MLB alleviated DN by recovering the dysfunction of gut microbiota and their associated metabolites in colon content, such as short-chain fatty acids and amino acids. Moreover, MLB significantly decreased uremic toxin levels in plasma, especially the p-cresyl sulfate. We further discovered that MLB could affect the metabolism of p- cresyl sulfate by suppressing the formation of its intestinal precursors, i.e. the microbiota-mediated conversion from 4-hydroxyphenylacetate to p-cresol. In addition, the inhibition effects of MLB were confirmed. MLB and its metabolite danshensu exhibited inhibitory effects on p-cresol formation mediated by three strains belonging to the genus Clostridium, Bifidobacterium, and Fusobacterium, respectively. Meanwhile, MLB decreased the levels of p-cresyl sulfate in plasma and p-cresol in feces caused by rectal administration of tyrosine in mice. To summarize, the results indicated that MLB ameliorated DN through modulating gut microbiota-associated p-cresyl sulfate metabolism. Together, this study provides new insights on the microbiota-targeted mechanism of MLB in intervening DN and a new strategy in lowering plasma uremic toxins by blocking the formation of their pre-cursors in intestine.
WOS关键词CHAIN FATTY-ACIDS ; KIDNEY-DISEASE ; SALVIA-MILTIORRHIZA ; INTESTINAL MICROBIOTA ; AMINO-ACIDS ; METABOLITES ; ALTERS ; TRYPTOPHAN ; PLASMA
资助项目National Natural Science Foundation of China[81803610] ; Youth Innovation Promotion Association, Chinese Academy of Sciences[2019282] ; Science andTechnology Commission of Shanghai Municipality (STCSM)[19431900900]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER
WOS记录号WOS:001021206900001
源URL[http://119.78.100.183/handle/2S10ELR8/306430]  
专题新药研究国家重点实验室
通讯作者Wang, Kai; Liu, Jia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310058, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Nanlin,Duan, Haonan,Feng, Yingying,et al. Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2023,953:12.
APA Zhu, Nanlin.,Duan, Haonan.,Feng, Yingying.,Xu, Wenwei.,Shen, Jianhua.,...&Liu, Jia.(2023).Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota.EUROPEAN JOURNAL OF PHARMACOLOGY,953,12.
MLA Zhu, Nanlin,et al."Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota".EUROPEAN JOURNAL OF PHARMACOLOGY 953(2023):12.

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来源：上海药物研究所

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