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Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study.

ABSTRACT: Radix Polygoni Multiflori (RPM) has been widely used to treat various diseases in Asian countries for many centuries. Although, stilbenes and anthraquinones, two major components of RPM, show various bioactive effects, it has been speculated that the idiosyncratic hepatotoxicity induced by RPM may be related to these constituents. However, information on the pharmacokinetics of stilbenes and anthraquinones at a subtoxic dose of RPM is limited. A simple and sensitive UPLC-MS/MS bioanalytical method for the simultaneous determination of 13 ingredients of RPM, including chrysophanol, emodin, aloe-emodin, rhein, physcion, questin, citreorosein, questinol, 2,3,5,4'-tetrahydroxystilbene-2-O-?-D-glucoside, torachrysone-8-O-glucoside, chrysophanol-8-O-?-D-glucoside, emodin-8-O-?-D-glucoside, and physcion-8-O-?-D-glucoside, in rat plasma was established. Acetonitrile was employed to precipitate the plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a waters HSS C18 column with a gradient elution using water and acetonitrile both containing 0.025% formic acid within a run time of 9?min. The constituents were detected in negative ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects, and stability. The lower limit of quantitation of the analytes was 0.1-1?ng/mL. The intrabatch and interbatch accuracies were 87.1-109%, and the precision was within the acceptable limits. The method was applied to a pharmacokinetic study after oral administration of RPM extract to rats at a subtoxic dose of 36?g/kg.

SUBMITTER: Cheng W

PROVIDER: S-EPMC7072103 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study.

Cheng Wenhao W Li Yinghui Y Yang Wei W Wu Siyang S Wei Mengmeng M Gao Yang Y Kang Chen C Zhang Shuofeng S Li Yingfei Y

International journal of analytical chemistry 20200303

Radix Polygoni Multiflori (RPM) has been widely used to treat various diseases in Asian countries for many centuries. Although, stilbenes and anthraquinones, two major components of RPM, show various bioactive effects, it has been speculated that the idiosyncratic hepatotoxicity induced by RPM may be related to these constituents. However, information on the pharmacokinetics of stilbenes and anthraquinones at a subtoxic dose of RPM is limited. A simple and sensitive UPLC-MS/MS bioanalytical meth ...[more]

PMID: 32190053

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Project description:Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.

Dataset Information

Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study.

Publications

Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study.

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