Paeoniflorin inhibits Th1 and Th17 cells in gut-associated lymphoid tissues to produce anti-arthritis activities
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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.
KeywordsPaeoniflorin Arthritis Th1 cell Th17 cell Gut lymph tissues
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).
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Conflicts of interest
The authors declare no competing financial interests.
- Fei F 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 Anal Technol Biomed Life Sci 1022:30–37. https://doi.org/10.1016/j.jchromb.2016.04.005 CrossRefGoogle Scholar
- Komatsu N, Takayanagi H (2012) Autoimmune arthritis: the interface between the immune system and joints. Adv Immunol 115:45–71. https://doi.org/10.1016/B978-0-12-394299-9.00002-3 CrossRefPubMedGoogle Scholar
- Sun S, Zhu L, Hu Y, Liu Y (2018) Studies on the metabolism of paeoniflorin in human intestinal microflora by high performance liquid chromatography/electrospray ionization/fourier transform ion cyclotron resonance mass spectrometry and quadrupole time-of-flight mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 1085:63–71. https://doi.org/10.1016/j.jchromb.2018.03.042 CrossRefGoogle Scholar
- Wu H, Wei W, Song LH, Zhang LL, Chen Y, Hu XY (2007) Paeoniflorin induced immune tolerance of mesenteric lymph node lymphocytes via enhancing beta 2-adrenergic receptor desensitization in rats with adjuvant arthritis. Int Immunopharmacol 7:662–673. https://doi.org/10.1016/j.intimp.2007.01.019 CrossRefPubMedGoogle Scholar