PMID:
Inflammopharmacology. 2019 Jul 15. Epub 2019 Jul 15. PMID: 31309485
Abstract Title:
Paeoniflorin inhibits Th1 and Th17 cells in gut-associated lymphoid tissues to produce anti-arthritis activities.
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