Simultaneous Quantification of Multiple Active Components of the Combination of Ginkgo Ketoester Tablet and Donepezil in Four Biological Matrices from Dementia Mice: Application to Study the Distribution Patterns of the Two Drugs Based on “Brain-Gut” Axis

34 Pages Posted: 6 Oct 2021

See all articles by Gui-Sheng Zhou

Gui-Sheng Zhou

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Jing Zhang

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Xiao-Yu Huan

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Yu Zhuang

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Shi-Yu Xu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Jia-Shuai Liu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Ya-Jie Tan

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Hui-Juan Tao

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Jia-Qian Chen

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Zong-Jin Pu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Zhen-Hua Zhu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Xu-Qin Shi

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Yuiping Tang

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization; Nanjing University of Chinese Medicine (NJUCM) - Key Laboratory for High Technology Research of TCM Formulae; Shaanxi University of Chinese Medicine

Jin-Ao Duan

Nanjing University of Chinese Medicine (NJUCM) - National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine

Abstract

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer’s disease (AD). The aim of this study was undertaken to investigate anti-dementia effects of two drugs alone and in combination through monitoring the distribution patterns of active components in the important biological matrices based on the theory of “brain-gut” axis. A rapid and sensitive analytical method was developed for simultaneous quantification of 38 active compounds in the biological matrices at trace levels using ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP Ò /MS 2 ). Under the optimized conditions, good chromatographic separation of 38 target compounds was achieved within 14 min, with acceptable linearity, limits of detections and quantifications, precision, stability, extraction recovery and matrix effects. The developed analytical method was used to quantify 38 active components in brain, plasma, intestinal and intestinal contents from AD mice treated with GT alone, donepezil alone, and the combination of two drugs. The result showed that that the combination group enhanced anti-dementia active compounds (including caffeic acid, isoginkgetin and sciadopitysin) and reduced the toxic compounds (such as GAs) entering into target tissues. These findings might be a reason for the increasing anti-dementia efficiency and reducing toxicity in the combination of GT and donepezil. In addition, the presented UHPLC-QTRAP Ò /MS 2 method might be used to monitor the target active compounds from different clinical biological fluids in the further study.

Note:
Funding Information: This work was supported by National Natural Science Foundation of China (No. 81803699), Natural Science Foundation of Jiangsu Province (No. BK20171068), Natural Science Foundation of Nanjing University of Chinese Medicine (No. NZY81803699), Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (No. 012092002006-4), China Agriculture Research System of MOF and MARA (CARS-21), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Declaration of Interests: There are no conflicts to declare.

Ethics Approval Statement: The experimental procedures were strictly conducted in accordance with ethical principle of animal, and the related protocol was reviewed and approved by the Animal Experimental Ethical Committee of Nanjing University of Chinese Medicine. The approval ethical file number was No. 201906A023.

Keywords: DementiaDonepezilGinkgo ketoester tablet"Brain-gut" axisMultiple active components

Suggested Citation

Zhou, Gui-Sheng and Zhang, Jing and Huan, Xiao-Yu and Zhuang, Yu and Xu, Shi-Yu and Liu, Jia-Shuai and Tan, Ya-Jie and Tao, Hui-Juan and Chen, Jia-Qian and Pu, Zong-Jin and Zhu, Zhen-Hua and Shi, Xu-Qin and Tang, Yuiping and Tang, Yuiping and Duan, Jin-Ao, Simultaneous Quantification of Multiple Active Components of the Combination of Ginkgo Ketoester Tablet and Donepezil in Four Biological Matrices from Dementia Mice: Application to Study the Distribution Patterns of the Two Drugs Based on “Brain-Gut” Axis. Available at SSRN: https://ssrn.com/abstract=3937061 or http://dx.doi.org/10.2139/ssrn.3937061

Gui-Sheng Zhou (Contact Author)

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Jing Zhang

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Xiao-Yu Huan

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Yu Zhuang

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Shi-Yu Xu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Jia-Shuai Liu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Ya-Jie Tan

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Hui-Juan Tao

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Jia-Qian Chen

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Zong-Jin Pu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization

Nanjing
China

Zhen-Hua Zhu

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Xu-Qin Shi

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Yuiping Tang

Nanjing University of Chinese Medicine (NJUCM) - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization ( email )

Nanjing
China

Nanjing University of Chinese Medicine (NJUCM) - Key Laboratory for High Technology Research of TCM Formulae ( email )

Nanjing
China

Shaanxi University of Chinese Medicine ( email )

Xianyang
China

Jin-Ao Duan

Nanjing University of Chinese Medicine (NJUCM) - National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine ( email )

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