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Inflammopharmacology

, Volume 27, Issue 6, pp 1193–1203 | Cite as

Paeoniflorin inhibits Th1 and Th17 cells in gut-associated lymphoid tissues to produce anti-arthritis activities

  • Fei Fei
  • Li-xiang Aa
  • Qi Qi
  • Run-bin Sun
  • Cai-xia Yan
  • Ji-ye AaEmail author
  • Guang-ji Wang
Original Article

Abstract

Paeoniflorin shows distinct anti-arthritis and immunoregulatory activities, but its rather low bioavailability via oral administration greatly challenges its known mechanism of in vivo activity. Our data showed that oral administration, instead of intraperitoneal injection, of paeoniflorin significantly reduced the polyarthritis index by 44.4%, reduced paw swelling by 18.4% and delayed the onset of arthritis in collagen-induced arthritis (CIA) mice. Oral paeoniflorin treatment also downregulated the systemic pro-inflammatory cytokines IL-6 (by 52.2%), TNF-α (by 57.7%) and IL-1β (by 34.1%). A pharmacokinetic study revealed that the maximal plasma concentration of paeoniflorin after oral administration was 4.8 ± 1.9 μM in the CIA mice, much lower than the effective concentration in vitro (30 μM). In contrast, paeoniflorin was highly concentrated in the gut content, intestine and Peyer’s patches. T cell analysis showed that paeoniflorin markedly reduced transcription factors of Th1 and Th17, inhibited Th1 by 22.2% and 23.1% and Th17 by 43.2% and 25.4% (p < 0.05) in the mesenteric lymph node and Peyer’s patches, respectively. Paeoniflorin did not have a significant impact on Th1 and Th17 in the spleen. For the first time, these data suggest that paeoniflorin accumulates in the intestine and primarily modulates Th1 and Th17 responses in the mesenteric lymph nodes and Peyer’s patches, rather than in the spleen, to exert anti-arthritis effects.

Keywords

Paeoniflorin Arthritis Th1 cell Th17 cell Gut lymph tissues 

Notes

Acknowledgements

This study was financially supported by the National Natural Science Foundation of the People’s Republic of China (81573495, 81530098), the Key Technology Projects of China “Creation of New Drugs” (2017ZX09301013, 2015ZX09501001), and the double First-Rate Innovative Team (CPU2018GF01).

Compliance with ethical standards

Conflicts of interest

The authors declare no competing financial interests.

Supplementary material

10787_2019_615_MOESM1_ESM.docx (88 kb)
Supplementary material 1 (DOCX 87 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Fei Fei
    • 1
  • Li-xiang Aa
    • 1
  • Qi Qi
    • 1
  • Run-bin Sun
    • 1
  • Cai-xia Yan
    • 1
  • Ji-ye Aa
    • 1
    Email author
  • Guang-ji Wang
    • 1
  1. 1.Jiangsu Province Key Laboratory of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina

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