The Pharmacokinetics and Tissue Distributions of Nine Steroidal Saponins from Paris polyphylla in Rats

Abstract

Background and Objectives

Paris polyphylla (P. polyphylla) is a herb widely used in traditional Chinese medicine to treat various diseases. This study used ultrahigh-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to study the pharmacokinetics and tissue distributions of nine steroidal saponins from P. polyphylla.

Methods

P. polyphylla extract was administered to rats intravenously (i.v.) and orally (p.o.). The concentrations of the nine main bioactive components of the extract were determined in plasma and tissue samples using UPLC–MS/MS. The nine saponin compounds were also incubated in an anaerobic environment with intestinal flora suspension solution to investigate hydrolysis by intestinal flora.

Results

After oral administration of the P. polyphylla extract, polyphyllin VII was found to have the highest maximum concentration (Cmax, 17.0 ± 2.24 µg/L) of all nine components, followed by the Cmax values of dioscin (16.17 ± 0.64 µg/L) and polyphyllin H (11.75 ± 1.28 µg/L), while the Cmax values of polyphyllin I, polyphyllin II, progenin III, polyphyllin IV, gracillin, and polyphyllin were less than 10 µg/L. The bioavailabilities of all nine components were less than 1%. All the compounds were hydrolyzed by intestinal flora and were predominantly distributed in the liver and lungs.

Conclusions

The nine compounds presented different pharmacokinetic parameter values, and multiple administrations did not accumulate in the body. The bioavailabilities of the compounds were low, partly because of hydrolysis by intestinal flora. The nine compounds were mainly distributed in the liver and lungs, which may be target organs.

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Authors

Contributions

All authors contributed to the article as follows: PL conceived and designed the experiments; the experiments were performed to equal extents by WL and MP; PHZ and TZh analyzed the data; and FY and LYH performed the chromatographic analysis of the plasma and biosamples. All authors read and approved the final published version of the manuscript.

Corresponding author

Correspondence to Pan Lei.

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Funding

This work was supported by the Hubei Provincial Technology Innovation Project (no. 2017ACA176) and the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (grant no. WDCM2018003).

Conflicts of interest

The authors declare no conflicts of interest.

Ethics approval

All animal experimental procedures in this study were performed according to the institutional guidelines of the Animal Care and Use Committee of Taihe Hospital, Hubei University of Medicine (Hubei, PR China). The protocol was approved by the Animal Laboratory Committee of Taihe Hospital, Hubei University of Medicine.

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Lu, W., Pan, M., Zhang, P. et al. The Pharmacokinetics and Tissue Distributions of Nine Steroidal Saponins from Paris polyphylla in Rats. Eur J Drug Metab Pharmacokinet (2020). https://doi.org/10.1007/s13318-020-00633-5

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