Abstract

There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography–mass spectrometry (UPLC-MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

Highlights

  • Peony (Paeonialactiflora Pall, PLP; family Ranunculaceae) has been widely used for treating rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and Molecules 2016, 21, 874; doi:10.3390/molecules21070874 www.mdpi.com/journal/moleculesPeony (Paeonialactiflora Pall, PLP; family Ranunculaceae) has been widely used for treating rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms in in China, The major spasmsChina, Korea, Korea, JapanJapan and and the the Southeast Southeast Asian Asian countries.countries

  • A UPLC-electrospray ionization (ESI)-MS/MS method has been developed for the simultaneous determination of PF and AF from PF, AF and total peony glucosides (TPG) preparations in rat plasma

  • The results indicated that this method could be successfully used for studying both the pharmacokinetic interactions of PF, AF and TPG after intragastric administration to rats, and the pharmacokinetic comparison of PF and AF between hypoxic and normoxic rats

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Summary

Introduction

Peony (Paeonialactiflora Pall, PLP; family Ranunculaceae) has been widely used for treating rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and Molecules 2016, 21, 874; doi:10.3390/molecules21070874 www.mdpi.com/journal/moleculesPeony (Paeonialactiflora Pall, PLP; family Ranunculaceae) has been widely used for treating rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms in in China, The major spasmsChina, Korea, Korea, JapanJapan and and the the Southeast Southeast Asian Asian countries.countries. Peony (Paeonialactiflora Pall, PLP; family Ranunculaceae) has been widely used for treating rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and Molecules 2016, 21, 874; doi:10.3390/molecules21070874 www.mdpi.com/journal/molecules. Peony (Paeonialactiflora Pall, PLP; family Ranunculaceae) has been widely used for treating rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms in in China, The major spasms. Japan and and the the Southeast Southeast Asian Asian countries. The major active active components components of of peony radix extracts (TPG). For treating these diseases are monoterpene glycosides, galloyl peony radix extracts (TPG) for treating these diseases are monoterpene glycosides, galloyl glucoses glucoses and phenolic phenoliccompounds compounds[1,2,3,4,5]. The ethanol/water extracts of Peony are known thepeony total and. For treating these diseases are monoterpene glycosides, galloyl peony radix extracts (TPG) for treating these diseases are monoterpene glycosides, galloyl glucoses glucoses and phenolic phenoliccompounds compounds[1,2,3,4,5]. [1,2,3,4,5].

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