A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS

Kai-Xin-San (KXS) is a classic formula for the treatment of Alzheimer’s disease (AD). KXS has been widely used to treat emotional diseases; however, its active components remain unknown. There have been some reports about the efficacy and metabolic analysis of KXS, which are mainly based on studying...

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Main Authors: Lin Yang, Jian Liang, Qin Zheng, Lifen Zhou, Yongchang Xiong, Huijuan Wang, Jinbin Yuan
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/16/1/30
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author Lin Yang
Jian Liang
Qin Zheng
Lifen Zhou
Yongchang Xiong
Huijuan Wang
Jinbin Yuan
author_facet Lin Yang
Jian Liang
Qin Zheng
Lifen Zhou
Yongchang Xiong
Huijuan Wang
Jinbin Yuan
author_sort Lin Yang
collection DOAJ
description Kai-Xin-San (KXS) is a classic formula for the treatment of Alzheimer’s disease (AD). KXS has been widely used to treat emotional diseases; however, its active components remain unknown. There have been some reports about the efficacy and metabolic analysis of KXS, which are mainly based on studying normal animals. The current work first established an AD rat model by injecting D-galactose into the abdominal cavity and injecting Aβ<sub>25–35</sub> into the hippocampus on both sides, followed by intragastric administration of KXS for a consecutive week; then, the analytical method for ethanol extraction from the serum of normal and model rats was developed using UPLC-LTQ-Orbitrap-MS; finally, the transitional components in the blood were systematically compared and analyzed by multivariate statistical analysis. A total of 36 components of KXS were identified in the rat serum of the normal group, including 24 prototype components (including ginsenosides, triterpenoid acids of <i>Poria cocos</i>, polygala saponins, polygala xanthones and polygala ester) and 13 metabolites (including desugar, hydration and oxidation products of ginsenosides, triterpenoid acid hydroxylation, deoxygenation, demethylation, desaturation, and glycine-conjugated products of <i>Poria cocos</i>). Twenty KXS-relevant components were detected in the rat serum of the model group, including 11 prototypes and 9 metabolites. The normal group and the model group shared 12 common components, including 9 prototypes and 3 metabolites. The intestinal microecological balance of the model rats probably was destroyed, affecting the absorption/metabolism of saponins by the body, which resulted in fewer transitional components in the model group. This study reflected the drug-body interaction from an objective and accurate perspective, offering references and insights for elucidating the basis of active components and mechanism of action of KXS for treating AD.
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spelling doaj.art-b93af8d0dea442d89c380bb9b56ae2d02023-11-30T23:54:48ZengMDPI AGPharmaceuticals1424-82472022-12-011613010.3390/ph16010030A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MSLin Yang0Jian Liang1Qin Zheng2Lifen Zhou3Yongchang Xiong4Huijuan Wang5Jinbin Yuan6Key Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaResearch Center for Traditional Chinese Medicine Resources and Ethnic Minority Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaKey Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaKey Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaKey Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaKey Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaKey Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaKai-Xin-San (KXS) is a classic formula for the treatment of Alzheimer’s disease (AD). KXS has been widely used to treat emotional diseases; however, its active components remain unknown. There have been some reports about the efficacy and metabolic analysis of KXS, which are mainly based on studying normal animals. The current work first established an AD rat model by injecting D-galactose into the abdominal cavity and injecting Aβ<sub>25–35</sub> into the hippocampus on both sides, followed by intragastric administration of KXS for a consecutive week; then, the analytical method for ethanol extraction from the serum of normal and model rats was developed using UPLC-LTQ-Orbitrap-MS; finally, the transitional components in the blood were systematically compared and analyzed by multivariate statistical analysis. A total of 36 components of KXS were identified in the rat serum of the normal group, including 24 prototype components (including ginsenosides, triterpenoid acids of <i>Poria cocos</i>, polygala saponins, polygala xanthones and polygala ester) and 13 metabolites (including desugar, hydration and oxidation products of ginsenosides, triterpenoid acid hydroxylation, deoxygenation, demethylation, desaturation, and glycine-conjugated products of <i>Poria cocos</i>). Twenty KXS-relevant components were detected in the rat serum of the model group, including 11 prototypes and 9 metabolites. The normal group and the model group shared 12 common components, including 9 prototypes and 3 metabolites. The intestinal microecological balance of the model rats probably was destroyed, affecting the absorption/metabolism of saponins by the body, which resulted in fewer transitional components in the model group. This study reflected the drug-body interaction from an objective and accurate perspective, offering references and insights for elucidating the basis of active components and mechanism of action of KXS for treating AD.https://www.mdpi.com/1424-8247/16/1/30Kai-Xin-Sanserum pharmacochemistryAD-model ratultra-high performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS)multivariate statistical analysisprototype component
spellingShingle Lin Yang
Jian Liang
Qin Zheng
Lifen Zhou
Yongchang Xiong
Huijuan Wang
Jinbin Yuan
A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS
Pharmaceuticals
Kai-Xin-San
serum pharmacochemistry
AD-model rat
ultra-high performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS)
multivariate statistical analysis
prototype component
title A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS
title_full A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS
title_fullStr A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS
title_full_unstemmed A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS
title_short A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS
title_sort comparative study of serum pharmacochemistry of kai xin san in normal and ad rats using uplc ltq orbitrap ms
topic Kai-Xin-San
serum pharmacochemistry
AD-model rat
ultra-high performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS)
multivariate statistical analysis
prototype component
url https://www.mdpi.com/1424-8247/16/1/30
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