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Planta Med 2023; 89(10): 940-951
DOI: 10.1055/a-2085-2367
Biological and Pharmacological Activity
Original Papers

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine

Yajuan Bi
1   School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P. R. China
,
Yanchao Xing
2   State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
3   School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, P. R. China
,
Chunshan Gui
4   College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, P. R. China
,
Yiqing Tian
1   School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P. R. China
,
Mingzhe Zhang
1   School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P. R. China
,
Yao Yao
5   School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
,
Ge Hu
1   School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P. R. China
,
Lifeng Han
2   State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
,
Feng He
6   School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, P. R. China
,
Youcai Zhang
1   School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P. R. China
› Author AffiliationsThis work was supported by the grants from the School-Enterprise Cooperation Project (2021GFW-0278 & 2020GKF-0364) and the National Natural Science Foundation of China (NSFC) grant (No. 82274031).
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Abstract

Traditional Chinese medicine injections have been widely used in China for the treatment of various diseases. Transporter-mediated drug-drug interactions are a major contributor to adverse drug reactions. However, the research on transporter-mediated Traditional Chinese medicine injection-drug interactions is limited. Shuganning injection is a widely used Traditional Chinese medicine injection for treating various liver diseases. In this study, we investigated the inhibitory effect of Shuganning injection and its four main ingredients (baicalin, geniposide, chlorogenic acid, and oroxylin A) on 9 drug transporters. Shuganning injection strongly inhibited organic anion transporter 1 and organic anion transporter 3 with IC50 values < 0.1% (v/v), and moderately inhibited organic anion transporter 2, organic anion transporting-polypeptide 1B1, and organic anion transporting-polypeptide 1B3 with IC50 values < 1.0%. Baicalin, the most abundant bioactive ingredient in the Shuganning injection, was identified as both an inhibitor and substrate of organic anion transporter 1, organic anion transporter 3, and organic anion transporting-polypeptide 1B3. Oroxylin A had the potential to act as both an inhibitor and substrate of organic anion transporting-polypeptide 1B1 and organic anion transporting-polypeptide 1B3. In contrast, geniposide and chlorogenic acid had no significant inhibitory effect on drug transporters. Notably, Shuganning injection markedly altered the pharmacokinetics of furosemide and atorvastatin in rats. Using Shuganning injection as an example, our findings support the implementation of transporter-mediated Traditional Chinese medicine injection-drug interactions in the development of Traditional Chinese medicine injection standards.

Key words

Transporter - Shuganning injection - drug-drug interaction - Artemisia capillaris - Gardenia jasminoides - Isatis tinctoria - Ganoderma lucidum

Supporting Information

    Detailed information of fluorescent substrates, SGNI active ingredient concentrations, LC-MS/MS method validation data, and uptake kinetic studies of baicalin and oroxylin A are available as Supporting Information.

  • Supporting Information


Publication History

Received: 02 December 2022

Accepted after revision: 21 April 2023

Article published online:
26 May 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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