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Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen)

文献类型：期刊论文

作者Lu, Jun-Lan3,4; Zeng, Xue-Shan3,4; Zhou, Xin3,4; Yang, Jun-Ling2,3,4; Ren, Ling-Ling2,3; Long, Xin-Yu2,3; Wang, Feng-Qing3; Olaleye, Olajide E.3; Tian, Nan-Nan3,4; Zhu, Ya-Xuan3,4
刊名FRONTIERS IN PHARMACOLOGY
出版日期2022-05-10
卷号13页码:13
关键词Danshen Salvia miltiorrhiza phenolic acid hepatic transporter renal transporter
DOI10.3389/fphar.2022.911982
通讯作者Dong, Jia-Jia(dongjiajia300512@njucm.edu.cn) ; Jia, Wei-Wei(weiweijia@simm.ac.cn) ; Li, Chuan(chli@simm.ac.cn)
英文摘要Phenolic acids are cardiovascular constituents (originating from the Chinese medicinal herb Salvia miltiorrhiza root/Danshen) of DanHong and many other Danshen-containing injections. Our earlier pharmacokinetic investigation of DanHong suggested that hepatic and/or renal uptake of the Danshen compounds was the crucial steps in their systemic elimination. This investigation was designed to survey the molecular basis underlying hepatobiliary and renal excretion of the Danshen compounds, i.e., protocatechuic acid, tanshinol, rosmarinic acid, salvianolic acid D, salvianolic acid A, lithospermic acid, and salvianolic acid B. A large battery of human hepatic and renal transporters were screened for transporting the Danshen compounds and then characterized for the uptake kinetics and also compared with associated rat transporters. The samples were analyzed by liquid chromatography/mass spectrometry. Because the Danshen phenolic acids are of poor or fairly good membrane permeability, their elimination via the liver or kidneys necessitates transporter-mediated hepatic or renal uptake from blood. Several human transporters were found to mediate hepatic and/or renal uptake of the Danshen compounds in a compound-molecular-mass-related manner. Lithospermic acid and salvianolic acid B (both >500 Da) underwent systemic elimination, initiated by organic anion-transporting polypeptide (OATP)1B1/OATP1B3-mediated hepatic uptake. Rosmarinic acid and salvianolic acids D (350-450 Da) underwent systemic elimination, initiated by OATP1B1/OATP1B3/organic anion transporter (OAT)2-mediated hepatic uptake and by OAT1/OAT2-mediated renal uptake. Protocatechuic acid and tanshinol (both <200 Da) underwent systemic elimination, initiated by OAT1/OAT2-mediated renal uptake and OAT2-mediated hepatic uptake. A similar scenario was observed with the rat orthologs. The investigation findings advance our understanding of the disposition of the Danshen phenolic acids and could facilitate pharmacokinetic research on other Danshen-containing injections.
WOS关键词SYSTEMIC EXPOSURE ; HERBAL MEDICINES ; DRUG ; DISPOSITION ; TANSHINOL ; PHARMACOKINETICS ; TRANSPORTERS ; METABOLISM ; MECHANISMS
资助项目National Key R&D Program of China[2018YFC1704500] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202009] ; National Natural Science Foundation of China[81673582] ; National Natural Science Foundation of China[82192912] ; National Natural Science Foundation of China[82104700]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000802263200001
源URL[http://119.78.100.183/handle/2S10ELR8/301225]  
专题新药研究国家重点实验室
通讯作者Dong, Jia-Jia; Jia, Wei-Wei; Li, Chuan
作者单位1.Nanjing Univ Chinese Med, Coll Pharm, Nanjing, Peoples R China
2.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
4.Tianjin Univ Tradit Chinese Med, Grad Sch, Tianjin, Peoples R China
推荐引用方式
GB/T 7714		 Lu, Jun-Lan,Zeng, Xue-Shan,Zhou, Xin,et al. Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen)[J]. FRONTIERS IN PHARMACOLOGY,2022,13:13.
APA Lu, Jun-Lan.,Zeng, Xue-Shan.,Zhou, Xin.,Yang, Jun-Ling.,Ren, Ling-Ling.,...&Li, Chuan.(2022).Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen).FRONTIERS IN PHARMACOLOGY,13,13.
MLA Lu, Jun-Lan,et al."Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen)".FRONTIERS IN PHARMACOLOGY 13(2022):13.

入库方式： OAI收割

来源：上海药物研究所

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