Skip to main content
Top
Published in: Inflammopharmacology 5/2019

01-10-2019 | Original Article

The tissue distribution and excretion study of paeoniflorin-6′-O-benzene sulfonate (CP-25) in rats

Authors: Mingyi Zhao, Peng Zhou, Jun Yu, Asenso James, Feng Xiao, Chun Wang, Wei Wei

Published in: Inflammopharmacology | Issue 5/2019

Login to get access

Abstract

Paeoniflorin-6′-O-benzene sulfonate (code: CP-25) is a novel ester derivative of paeoniflorin (Pae). Compared to Pae, CP-25 has higher lipid solubility, bioavailability and better bioactivity. However, the tissue distribution and excretion of CP-25 still remain unknown. The LC–MS method was applied to investigate the tissue distribution and excretion of CP-25 in rats. As such, 50 mg/kg of CP-25 and Pae were administered to rats in multiple doses via an oral route. CP-25 and Pae were distributed widely and rapidly in all the tested tissues. Compared with Pae, the concentrations of CP-25 were almost increased evidently in most tissues. The highest CP-25 level was found in the liver (1476.33 ± 535.20 ng/g, male; 1970.38 ± 177.21 ng/g, female) at 3 h, and a high concentration of CP-25 was detected in male and female intestine, synovium, muscle, lung, and brain. Following a single oral dose of 50 mg/kg of CP-25 in rats, the total excretion of CP-25 was merely 21.8% (18.40, 3.19 and 0.22% for feces, bile and urine, respectively) in males; and was approximately 21.3% (14.04, 7.16 and 0.14% for feces, bile and urine, respectively) in females. The results indicated that the CP-25 concentration was higher in major tissues than Pae; CP-25 was primarily excreted through the feces; and there were gender-related differences in the tissue distribution and excretion.
Literature
go back to reference Almazroo OA, Miah MK, Venkataramanan R (2017) Drug metabolism in the liver. Clin Liver Dis 21:1–20CrossRef Almazroo OA, Miah MK, Venkataramanan R (2017) Drug metabolism in the liver. Clin Liver Dis 21:1–20CrossRef
go back to reference Anderson GD (2005) Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt) 14(1):19–29CrossRef Anderson GD (2005) Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt) 14(1):19–29CrossRef
go back to reference Anderson GD (2008) Gender differences in pharmacological response. Int Rev Neurobiol 83:1–10CrossRef Anderson GD (2008) Gender differences in pharmacological response. Int Rev Neurobiol 83:1–10CrossRef
go back to reference Chang Y, Wei W, Zhang L, Xu HM (2009) Effects and mechanisms of total glucosides of paeony on synoviocytes activities in rat collagen-induced arthritis. J Ethnopharmacol 121:43–48CrossRef Chang Y, Wei W, Zhang L, Xu HM (2009) Effects and mechanisms of total glucosides of paeony on synoviocytes activities in rat collagen-induced arthritis. J Ethnopharmacol 121:43–48CrossRef
go back to reference Chang Y, Zhang L, Wang C, Jia XY, Wei W (2011) Paeoniflorin inhibits function of synoviocytes pretreated by rIL-1α and regulates EP4 receptor expression. J Ethnopharmacol 137:1275–1282CrossRef Chang Y, Zhang L, Wang C, Jia XY, Wei W (2011) Paeoniflorin inhibits function of synoviocytes pretreated by rIL-1α and regulates EP4 receptor expression. J Ethnopharmacol 137:1275–1282CrossRef
go back to reference Chang Y, Jia X, Wei F et al (2016) CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage. Sci Rep 6:26239CrossRef Chang Y, Jia X, Wei F et al (2016) CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage. Sci Rep 6:26239CrossRef
go back to reference Chen JY, Wu HX, Chen Y et al (2012) Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through suppressing G-protein-coupled receptor kinase 2. Planta Med 78:665–671CrossRef Chen JY, Wu HX, Chen Y et al (2012) Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through suppressing G-protein-coupled receptor kinase 2. Planta Med 78:665–671CrossRef
go back to reference Demyanets S, Wojta J (2012) Sex differences in effects and use of anti-inflammatory drugs. Handb Exp Pharmacol 214:443–472CrossRef Demyanets S, Wojta J (2012) Sex differences in effects and use of anti-inflammatory drugs. Handb Exp Pharmacol 214:443–472CrossRef
go back to reference Fei F, Yang H, Peng Y et al (2016) Sensitive analysis and pharmacokinetic study of the isomers paeoniflorin and albiflorin after oral administration of total glucosides of white paeony capsule in rats. J Chromatogr B Analyt Technol Biomed Life Sci 1022:30–37CrossRef Fei F, Yang H, Peng Y et al (2016) Sensitive analysis and pharmacokinetic study of the isomers paeoniflorin and albiflorin after oral administration of total glucosides of white paeony capsule in rats. J Chromatogr B Analyt Technol Biomed Life Sci 1022:30–37CrossRef
go back to reference Jia XY, Chang Y, Sun XJ et al (2014) Total glucosides of paeony inhibit the proliferation of fibroblast-like synoviocytes through the regulation of G proteins in rats with collagen-induced arthritis. Int Immunopharmacol 18:1–6CrossRef Jia XY, Chang Y, Sun XJ et al (2014) Total glucosides of paeony inhibit the proliferation of fibroblast-like synoviocytes through the regulation of G proteins in rats with collagen-induced arthritis. Int Immunopharmacol 18:1–6CrossRef
go back to reference Jia XY, Wei F, Sun XJ et al (2016) CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4 + T cells. J Ethnopharmacol 189:194–201CrossRef Jia XY, Wei F, Sun XJ et al (2016) CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4 + T cells. J Ethnopharmacol 189:194–201CrossRef
go back to reference Li Y, Sheng K, Chen J et al (2015) Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25. Eur J Pharmacol 769:8–21CrossRef Li Y, Sheng K, Chen J et al (2015) Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25. Eur J Pharmacol 769:8–21CrossRef
go back to reference Liu ZQ, Zhou H, Liu L et al (2005) Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats. J Ethnopharmacol 99:61–67CrossRef Liu ZQ, Zhou H, Liu L et al (2005) Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats. J Ethnopharmacol 99:61–67CrossRef
go back to reference Liu ZQ, Jiang ZH, Liu L, Hu M (2006) Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenine. Pharm Res 23:2768–2780CrossRef Liu ZQ, Jiang ZH, Liu L, Hu M (2006) Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenine. Pharm Res 23:2768–2780CrossRef
go back to reference Soldin OP, Mattison DR (2009) Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 48(3):143–157CrossRef Soldin OP, Mattison DR (2009) Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 48(3):143–157CrossRef
go back to reference Wang C, Yuan J, Yang ZY, Nie XX, Song LH, Wei W (2012) Pharmacokinetics of paeoniflorin microemulsion after repeated dosing in rats with adjuvant arthritis. Pharmazie 67:997–1001PubMed Wang C, Yuan J, Yang ZY, Nie XX, Song LH, Wei W (2012) Pharmacokinetics of paeoniflorin microemulsion after repeated dosing in rats with adjuvant arthritis. Pharmazie 67:997–1001PubMed
go back to reference Wang C, Yuan J, Zhang LL, Wei W (2016) Pharmacokinetic comparisons of Paeoniflorin and Paeoniflorin-6′O-benzene sulfonate in rats via different routes of administration. Xenobiotica 46:1142–1150CrossRef Wang C, Yuan J, Zhang LL, Wei W (2016) Pharmacokinetic comparisons of Paeoniflorin and Paeoniflorin-6′O-benzene sulfonate in rats via different routes of administration. Xenobiotica 46:1142–1150CrossRef
go back to reference Wu H, Wei W, Song L, Zhang L, Chen Y, Hu X (2007) Paeoniflorin induced immune tolerance of mesenteric lymph node lymphocytes via enhancing beta 2-adrenergic receptor desensitization in rats with adjuvant arthritis. Int Immunopharmacol 7:662–673CrossRef Wu H, Wei W, Song L, Zhang L, Chen Y, Hu X (2007) Paeoniflorin induced immune tolerance of mesenteric lymph node lymphocytes via enhancing beta 2-adrenergic receptor desensitization in rats with adjuvant arthritis. Int Immunopharmacol 7:662–673CrossRef
go back to reference Xu HM, Wei W, Jia XY, Chang Y, Zhang L (2007) Effects and mechanisms of total glucosides of paeony on adjuvant arthritis in rats. J Ethnopharmacol 109:442–448CrossRef Xu HM, Wei W, Jia XY, Chang Y, Zhang L (2007) Effects and mechanisms of total glucosides of paeony on adjuvant arthritis in rats. J Ethnopharmacol 109:442–448CrossRef
go back to reference Yang XD, Wang C, Zhou P et al (2016) Absorption characteristic of paeoniflorin-6′-Obenzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats. Xenobiotica 46:775–783CrossRef Yang XD, Wang C, Zhou P et al (2016) Absorption characteristic of paeoniflorin-6′-Obenzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats. Xenobiotica 46:775–783CrossRef
go back to reference Yu J, Xiao F, Asenso J et al (2016) Simultaneous determination of paeoniflorin-60-Obenzene sulfonate (CP-25) and its active paeoniflorin (Pae) metabolite in rat plasma using UPLC-MS/MS: an application for pharmacokinetic studies. RSC Adv 6:113209CrossRef Yu J, Xiao F, Asenso J et al (2016) Simultaneous determination of paeoniflorin-60-Obenzene sulfonate (CP-25) and its active paeoniflorin (Pae) metabolite in rat plasma using UPLC-MS/MS: an application for pharmacokinetic studies. RSC Adv 6:113209CrossRef
go back to reference Zhang LL, Wei W, Wang NP et al (2008) Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast-like synoviocytes of collagen induced arthritic rats. Inflamm Res 57:388–395CrossRef Zhang LL, Wei W, Wang NP et al (2008) Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast-like synoviocytes of collagen induced arthritic rats. Inflamm Res 57:388–395CrossRef
go back to reference Zhang F, Shu JL, Li Y et al (2017a) CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agent. Front Pharmacol 8:933CrossRef Zhang F, Shu JL, Li Y et al (2017a) CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agent. Front Pharmacol 8:933CrossRef
go back to reference Zhang H, Qi Y, Yuan Y et al (2017b) Paeoniflorin ameliorates experimental autoimmune encephalomyelitis via inhibition of dendritic cell function and Th17 cell differentiation. Sci Rep 7:41887CrossRef Zhang H, Qi Y, Yuan Y et al (2017b) Paeoniflorin ameliorates experimental autoimmune encephalomyelitis via inhibition of dendritic cell function and Th17 cell differentiation. Sci Rep 7:41887CrossRef
go back to reference Zheng YQ, Wei W (2005) Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes. Int Immunopharmacol 5:1560–1573CrossRef Zheng YQ, Wei W (2005) Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes. Int Immunopharmacol 5:1560–1573CrossRef
go back to reference Zheng YQ, Wei W, Zhu L, Liu JX (2007) Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats. Inflamm Res 56:182–188CrossRef Zheng YQ, Wei W, Zhu L, Liu JX (2007) Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats. Inflamm Res 56:182–188CrossRef
go back to reference Zhu L, Wei W, Zheng YQ, Jia XY (2005) Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen induced arthritis. Inflamm Res 54:211–220CrossRef Zhu L, Wei W, Zheng YQ, Jia XY (2005) Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen induced arthritis. Inflamm Res 54:211–220CrossRef
Metadata
Title
The tissue distribution and excretion study of paeoniflorin-6′-O-benzene sulfonate (CP-25) in rats
Authors
Mingyi Zhao
Peng Zhou
Jun Yu
Asenso James
Feng Xiao
Chun Wang
Wei Wei
Publication date
01-10-2019
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 5/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-018-0463-3

Other articles of this Issue 5/2019

Inflammopharmacology 5/2019 Go to the issue