Magnesium lithospermate B improves the gut microbiome and bile acid metabolic profiles in a mouse model of diabetic nephropathy

doi:10.1038/s41401-018-0029-3

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	Magnesium lithospermate B improves the gut microbiome and bile acid metabolic profiles in a mouse model of diabetic nephropathy
	Zhao, Jing1 ; Zhang, Qing-Li2 ; Shen, Jian-Hua1 ; Wang, Kai 3; Liu, Jia4
刊名	Acta pharmacologica Sinica
	2018-06-25
ISSN号	1745-7254
DOI	10.1038/s41401-018-0029-3
文献子类	Article
英文摘要	Magnesium lithospermate B (MLB) is a new drug marketed in China to treat angina, but its low oral bioavailability limits its clinical application to the intravenous route. Paradoxically, orally administered low-dose MLB was found to alleviate kidney injury in diabetic nephropathy (DN) rats, but its mechanism of action remains unknown. In recent years, the kidney-gut axis has been suspected to be involved in kidney damage pathogenesis, potentially representing a non-classical pathway for pharmacologic intervention. To ascertain whether MLB targets the kidney-gut axis, streptozotocin (STZ)-treated mice were prepared as a mouse model of DN. The STZ mice were treated with MLB (50 mg kg d, p.o.) for 8 weeks. Twenty-four-hour urinary albumin was detected to mirror kidney function. At week 4, 6, 8, feces were collected; bile acids (BAs) were quantified to examine the alterations in the BA metabolic profiles, and bacterial 16S rRNA gene fragments were sequenced to identify alterations in gut microbial composition. In STZ mice, 24-h urinary albumin levels and total fecal BAs, especially cholic acids (CAs) and deoxycholic acids (DCAs) were greatly increased, and the gut microbiome was dramatically shifted compared with control mice. Oral administration of MLB significantly decreased 24-h urinary albumin levels and total BAs, CAs and DCAs, and reversed CA:TCA (taurocholic acid) and DCA:CA ratios. It also changed the microbiome composition in STZ mice based on operational units. Thus the therapeutic effect of MLB on kidney injury might be attributed (at least partially) to its ability to modulate the disordered gut microbiome and BA metabolism.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266261]
专题	药物发现与设计中心上海药物代谢研究中心
通讯作者	Wang, Kai; Liu, Jia
作者单位	1.University of Chinese Academy of Sciences, Beijing, 100049, China; 2.Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, 201203, China; 3.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, 201203, China; 4.Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, 201203, China. jia
推荐引用方式 GB/T 7714	Zhao, Jing,Zhang, Qing-Li,Shen, Jian-Hua,et al. Magnesium lithospermate B improves the gut microbiome and bile acid metabolic profiles in a mouse model of diabetic nephropathy[J]. Acta pharmacologica Sinica,2018.
APA	Zhao, Jing,Zhang, Qing-Li,Shen, Jian-Hua,Wang, Kai,&Liu, Jia.(2018).Magnesium lithospermate B improves the gut microbiome and bile acid metabolic profiles in a mouse model of diabetic nephropathy.Acta pharmacologica Sinica.
MLA	Zhao, Jing,et al."Magnesium lithospermate B improves the gut microbiome and bile acid metabolic profiles in a mouse model of diabetic nephropathy".Acta pharmacologica Sinica (2018).