Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats

Shengxian Decotion (SXT), a well-known Traditional Chinese Medicine (TCM) formula composed of Astragali Radix, Bupleuri Radix, Cimicifugae Rhizoma, Anemarrhenae Rhizoma and Platycodonis Radix, is clinically considered as an effective formula against cardiovascular diseases. However, the exact effect...

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Autores principales:	Cuiyun Huang, Shi Qiu, Xiangcheng Fan, Guangyang Jiao, Xun Zhou, Mei Sun, Nan Weng, Shouhong Gao, Xia Tao, Feng Zhang, Wansheng Chen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Shengxian decoction Doxorubicin Chronic heart failure Comparative pharmacokinetic UHPLC-MS/MS Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9d224f68e14e49a9a57c4be5455a6c61
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spelling	oai:doaj.org-article:9d224f68e14e49a9a57c4be5455a6c612021-11-14T04:30:13ZEvaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats0753-332210.1016/j.biopha.2021.112354https://doaj.org/article/9d224f68e14e49a9a57c4be5455a6c612021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011380https://doaj.org/toc/0753-3322Shengxian Decotion (SXT), a well-known Traditional Chinese Medicine (TCM) formula composed of Astragali Radix, Bupleuri Radix, Cimicifugae Rhizoma, Anemarrhenae Rhizoma and Platycodonis Radix, is clinically considered as an effective formula against cardiovascular diseases. However, the exact effective substance of SXT in treating chronic heart failure (CHF) still remains unclear. In the current study, we investigated the benefit of SXT in doxorubicin (DOX)-induced CHF rats and established a UHPLC-MS/MS method to simultaneously determine 18 key compounds in a subsequent comparative pharmacokinetic study in normal and CHF rats. Histopathological studies, transmission electron microscopy, and echocardiography were applied to assess the therapeutic effect of SXT on DOX-induced CHF rats, which indicated that SXT significantly ameliorated DOX-induced CHF, similar to enalapril. In addition, we successfully established a UHPLC-MS/MS method to determine the pharmacokinetics of the components in rat plasma, which was validated with good linearity, inter-day and intra-day precisions and accuracies, matrix effects, extraction recovery, and stability values. Our results showed that only astragaloside IV showed increased plasma exposure in the CHF rats, while saikosaponin A, quercetin, timosaponin B-II, ferulic acid, isoferulic acid and formononetin decreased compared to their pharmacokinetic characteristics in the normal and CHF rats. This study demonstrates that SXT enjoys obvious therapeutic effect on DOX-induced CHF rats, and the altered metabolism of some compounds in SXT is affected by the pathological state of CHF rats. Our findings provide a better understanding of the in vivo exposure to complex compounds of SXT, supporting effective substance screening and further investigation of the therapeutic mechanism.Cuiyun HuangShi QiuXiangcheng FanGuangyang JiaoXun ZhouMei SunNan WengShouhong GaoXia TaoFeng ZhangWansheng ChenElsevierarticleShengxian decoctionDoxorubicinChronic heart failureComparative pharmacokineticUHPLC-MS/MSTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112354- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Shengxian decoction Doxorubicin Chronic heart failure Comparative pharmacokinetic UHPLC-MS/MS Therapeutics. Pharmacology RM1-950
spellingShingle	Shengxian decoction Doxorubicin Chronic heart failure Comparative pharmacokinetic UHPLC-MS/MS Therapeutics. Pharmacology RM1-950 Cuiyun Huang Shi Qiu Xiangcheng Fan Guangyang Jiao Xun Zhou Mei Sun Nan Weng Shouhong Gao Xia Tao Feng Zhang Wansheng Chen Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
description	Shengxian Decotion (SXT), a well-known Traditional Chinese Medicine (TCM) formula composed of Astragali Radix, Bupleuri Radix, Cimicifugae Rhizoma, Anemarrhenae Rhizoma and Platycodonis Radix, is clinically considered as an effective formula against cardiovascular diseases. However, the exact effective substance of SXT in treating chronic heart failure (CHF) still remains unclear. In the current study, we investigated the benefit of SXT in doxorubicin (DOX)-induced CHF rats and established a UHPLC-MS/MS method to simultaneously determine 18 key compounds in a subsequent comparative pharmacokinetic study in normal and CHF rats. Histopathological studies, transmission electron microscopy, and echocardiography were applied to assess the therapeutic effect of SXT on DOX-induced CHF rats, which indicated that SXT significantly ameliorated DOX-induced CHF, similar to enalapril. In addition, we successfully established a UHPLC-MS/MS method to determine the pharmacokinetics of the components in rat plasma, which was validated with good linearity, inter-day and intra-day precisions and accuracies, matrix effects, extraction recovery, and stability values. Our results showed that only astragaloside IV showed increased plasma exposure in the CHF rats, while saikosaponin A, quercetin, timosaponin B-II, ferulic acid, isoferulic acid and formononetin decreased compared to their pharmacokinetic characteristics in the normal and CHF rats. This study demonstrates that SXT enjoys obvious therapeutic effect on DOX-induced CHF rats, and the altered metabolism of some compounds in SXT is affected by the pathological state of CHF rats. Our findings provide a better understanding of the in vivo exposure to complex compounds of SXT, supporting effective substance screening and further investigation of the therapeutic mechanism.
format	article
author	Cuiyun Huang Shi Qiu Xiangcheng Fan Guangyang Jiao Xun Zhou Mei Sun Nan Weng Shouhong Gao Xia Tao Feng Zhang Wansheng Chen
author_facet	Cuiyun Huang Shi Qiu Xiangcheng Fan Guangyang Jiao Xun Zhou Mei Sun Nan Weng Shouhong Gao Xia Tao Feng Zhang Wansheng Chen
author_sort	Cuiyun Huang
title	Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
title_short	Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
title_full	Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
title_fullStr	Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
title_full_unstemmed	Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
title_sort	evaluation of the effect of shengxian decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/9d224f68e14e49a9a57c4be5455a6c61
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Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats

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