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Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule

文献类型：期刊论文

作者Lan, Xiao-fang2,3; Olaleye, Olajide E.3; Lu, Jun-lan2,3; Yang, Wei4; Du, Fei-fei3; Yang, Jun-ling3; Cheng, Chen3; Shi, Yan-hong3; Wang, Feng-qing3; Zeng, Xue-shan3
刊名ACTA PHARMACOLOGICA SINICA
出版日期2021-04-30
页码18
关键词LianhuaQingwen glycyrrhetic acid 24-hydroxyglycyrrhetic acid Gancao-induced pseudoaldosteronism licorice-induced pseudoaldosteronism 11β -hydroxysteroid dehydrogenase 2 COVID-19 colonic microbiota
ISSN号1671-4083
DOI10.1038/s41401-021-00651-2
通讯作者Jia, Wei-wei(weiweijia@simm.ac.cn) ; Li, Chuan(chli@simm.ac.cn)
英文摘要LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11 beta-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11 beta-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11 beta-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 mu mol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2(D); a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2(D). Circulating 8 and M2(D), having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11 beta-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2(D). This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.
WOS关键词SYSTEMIC EXPOSURE ; 3-MONOGLUCURONYL-GLYCYRRHETINIC ACID ; XUEBIJING INJECTION ; HERBAL MEDICINE ; GUT MICROBIOTA ; DISPOSITION ; METABOLITE ; TANSHINOL ; IMPACT ; RATS
资助项目National Key R&D Program of China[2018YFC1704500] ; National Natural Science Foundation of China[82074273] ; National Natural Science Foundation of China[81603380] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306] ; National Science & Technology Major Project of China 'Key New Drug Creation and Manufacturing Program'[2017ZX09301012-006]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000646094000002
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/296519]  
专题新药研究国家重点实验室
通讯作者Jia, Wei-wei; Li, Chuan
作者单位1.Hebei Yiling Chinese Med Res Inst, Shijiazhuang 050035, Hebei, Peoples R China
2.Tianjin Univ Tradit Chinese Med, Grad Sch, Tianjin 301617, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
推荐引用方式
GB/T 7714		 Lan, Xiao-fang,Olaleye, Olajide E.,Lu, Jun-lan,et al. Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule[J]. ACTA PHARMACOLOGICA SINICA,2021:18.
APA Lan, Xiao-fang.,Olaleye, Olajide E..,Lu, Jun-lan.,Yang, Wei.,Du, Fei-fei.,...&Li, Chuan.(2021).Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.ACTA PHARMACOLOGICA SINICA,18.
MLA Lan, Xiao-fang,et al."Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule".ACTA PHARMACOLOGICA SINICA (2021):18.

入库方式： OAI收割

来源：上海药物研究所

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