Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter
文献类型：期刊论文
| 作者 | Wang, YuKun1,2; Li, Jing1,2 ; Wu, Li1,2; Qin, XueMei1,2; Xie, Cen3; Gao, XiaoXia1,2
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| 刊名 | PHYTOTHERAPY RESEARCH
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| 出版日期 | 2023-06-15 |
| 页码 | 15 |
| 关键词 | bile acids enterohepatic circulation FXR-related genes saikosaponins |
| ISSN号 | 0951-418X |
| DOI | 10.1002/ptr.7927 |
| 通讯作者 | Gao, XiaoXia(gaoxiaoxia@sxu.edu.cn) |
| 英文摘要 | Radix Bupleuri exerts effective hepatoprotective and cholagogic effects through its Saikosaponins (SSs) component. Therefore, we attempted to determine the mechanism of saikosaponins used to promote bile excretion by studying their effects on intrahepatic bile flow, focusing on the synthesis, transport, excretion, and metabolism of bile acids. C57BL/6N mice were continuously gavaged with saikosaponin a (SSa), saikosaponin b(2) (SSb2), or saikosaponin D (SSd) (200 mg/kg) for 14 days. Liver and serum biochemical indices were determined using Enzyme-linked immunosorbent assay (ELISA) kits. In addition, an ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) was used to measure the levels of the 16 bile acids in the liver, gallbladder, and cecal contents. Furthermore, SSs pharmacokinetics and docking between SSs and farnesoid X receptor (FXR)-related proteins were analyzed to investigate the underlying molecular mechanisms. Administration of SSs and Radix Bupleuri alcohol extract (ESS) did not cause significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) levels. Saikosaponin-regulated changes in bile acid (BA) levels in the liver, gallbladder, and cecum were closely related to genes involved in BA synthesis, transport, and excretion in the liver. Pharmacokinetic studies indicated that SSs were characterized by rapid elimination (t(1/2) as 0.68-2.47 h), absorption (T-max as 0.47-0.78 h), and double peaks in the drug-time curves of SSa and SSb2. A molecular docking study revealed that SSa, SSb2, and SSd docked well with the 16 protein FXR molecules and target genes (<-5.2 kcal/mol). Collectively, saikosaponins may maintain BA homeostasis in mice by regulating FXR-related genes and transporters in the liver and intestine. |
| WOS关键词 | PPAR-ALPHA ; FXR ; METABOLISM ; INJURY ; PHARMACOLOGY ; HOMEOSTASIS ; PLASMA |
| 资助项目 | Basic Application Project of Shanxi Province[20210302123432] ; National Natural Science Foundation of China[82174099] ; Shanxi 1331 Project Key Collaborative Innovation Center ; Shanxi Provincial Key Laboratory of Famous Jinyao Redevelopment ; Key Laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education ; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province[202105D121009] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001007963200001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306281]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, XiaoXia |
| 作者单位 | 1.Shanxi Univ, Key Lab Chem Biol & Mol Engn, Minist Educ, Taiyuan, Peoples R China 2.Shanxi Univ, Modern Res Ctr Tradit Chinese Med, 92 WuCheng Rd, Taiyuan, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, YuKun,Li, Jing,Wu, Li,et al. Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter[J]. PHYTOTHERAPY RESEARCH,2023:15. |
| APA | Wang, YuKun,Li, Jing,Wu, Li,Qin, XueMei,Xie, Cen,&Gao, XiaoXia.(2023).Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter.PHYTOTHERAPY RESEARCH,15. |
| MLA | Wang, YuKun,et al."Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter".PHYTOTHERAPY RESEARCH (2023):15. |
入库方式： OAI收割
来源：上海药物研究所
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