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Basic Clin Pharmacol Toxicol. 2018 Apr 17. doi: 10.1111/bcpt.13025. [Epub ahead of print]

CP-25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets.

Gu F1,2,3, Xu S1,2,3, Zhang P1,2,3, Chen X1,2,3, Wu Y1,2,3, Wang C1,2,3, Gao M1,2,3, Si M1,2,3, Wang X1,2,3, Heinrich K1,2,3, Wu H1,2,3, Wei W1,2,3.

Author information

1
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, China.
2
Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, Anhui, China.
3
Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, Anhui, China.

Abstract

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune illness of the moisture-producing glands such as salivary glands that is characterized by various immune abnormalities. The aetiology of pSS remains unclear and there is no curative agent. In this study, we investigated the putative therapeutic effects on a NOD/Ltj mouse model of Sjögren's syndrome-like disorders of an ester derivative of paeoniflorin, paeoniflorin-6'O-benzene (termed CP-25). Our study showed that CP-25 alleviated effectively clinical manifestations in NOD/Ltj mice resulting, for example, in increased salivary flow and reduced histopathological scores. Furthermore, CP-25 decreased lymphocyte viability in NOD/Ltj mice and attenuated the infiltration of Th1 cells and Th2 cells into the salivary glands of NOD/Ltj mice. In the spleen on NOD/Ltj mice, CP-25 skewed the ratio of Th17 and regulatory T cells towards regulatory T cells. After treatment, concentrations of anti-La/SSB and IgG antibodies were reduced and the titre of the inflammatory cytokines IFN-γ, IL-4, IL-6 and IL-17A in the serum on NOD/Ltj mice was alleviated. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS by modulating T lymphocyte subsets. Future studies will validate the use of CP-25 as a therapeutic strategy for the treatment of pSS.

PMID:
29665238
DOI:
10.1111/bcpt.13025
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