Journal of ethnopharmacology · 2025
Ethanol precipitation process affects the pharmacokinetic characteristics of major active glycosides of Qiong-Yu-Gao: evidences in normal and cisplatin-induced acute kidney injury rats.
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Chen Lin-Xia, Wang Yao, Zhu Run-Wen, Zhou Jing, Shen Ji-Chen, Wu Cheng-Ying, Shen Hong, Qin Xiang-Ling, Long Fang, Li Song-Lin
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Qiong-Yu-Gao (QYG) is a classical formula that shows protective effects against cisplatin-induced acute kidney injury (AKI). Recent evidence indicates that iridoid glycosides and ginsenosides are the main active substances of QYG. In the production of modern Chinese medicine preparations, ethanol precipitation is a commonly applied but not fully verified refining process.
AIM OF STUDY: Pharmacokinetic profiling approaches were used for evaluating the rationality of ethanol precipitation process in the production of modern QYG preparations.
MATERIALS AND METHODS: Ethanol precipitation was used to prepare the glycoside-rich fraction (QYG-GS). UPLC-TQ-MS/MS methods were established for quantification of iridoid glycosides and ginsenosides of QYG in plasma and fecal samples. The pharmacokinetic profiles of major glycosides were characterized and compared after oral administration of QYG and QYG-GS in both normal and cisplatin-induced AKI rats.
RESULTS: Using the validated quantitative methods, 6 glycosides were determined in plasma samples, and 14 glycosides were determined in fecal samples. More significant pharmacokinetic differences were observed in AKI rats than in normal rats. The ethanol precipitation process significantly increased the Cmax and AUC0-t of catalpol, rehmannioside D, melittoside, leonuride and ginsenoside Rb1, and decreased the T1/2 and MRT0-t values, indicating the increased absorption and accelerated elimination. Additionally, ethanol precipitation significantly decreased the fecal contents of above compounds, but increased the fecal contents of compound K.
CONCLUSIONS: UPLC-TQ-MS methods were developed and validated for quantification and comparison of QYG glycosides in biological samples. The ethanol precipitation process significantly altered the pharmacokinetic profiles of major active glycosides in QYG, especially in AKI rats. The findings could provide a helpful reference for selection of ethanol precipitation process in the production of modern QYG preparations.
AIM OF STUDY: Pharmacokinetic profiling approaches were used for evaluating the rationality of ethanol precipitation process in the production of modern QYG preparations.
MATERIALS AND METHODS: Ethanol precipitation was used to prepare the glycoside-rich fraction (QYG-GS). UPLC-TQ-MS/MS methods were established for quantification of iridoid glycosides and ginsenosides of QYG in plasma and fecal samples. The pharmacokinetic profiles of major glycosides were characterized and compared after oral administration of QYG and QYG-GS in both normal and cisplatin-induced AKI rats.
RESULTS: Using the validated quantitative methods, 6 glycosides were determined in plasma samples, and 14 glycosides were determined in fecal samples. More significant pharmacokinetic differences were observed in AKI rats than in normal rats. The ethanol precipitation process significantly increased the Cmax and AUC0-t of catalpol, rehmannioside D, melittoside, leonuride and ginsenoside Rb1, and decreased the T1/2 and MRT0-t values, indicating the increased absorption and accelerated elimination. Additionally, ethanol precipitation significantly decreased the fecal contents of above compounds, but increased the fecal contents of compound K.
CONCLUSIONS: UPLC-TQ-MS methods were developed and validated for quantification and comparison of QYG glycosides in biological samples. The ethanol precipitation process significantly altered the pharmacokinetic profiles of major active glycosides in QYG, especially in AKI rats. The findings could provide a helpful reference for selection of ethanol precipitation process in the production of modern QYG preparations.