Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritis.

Abstract

Daphnetin extracted from Daphne odora Var. marginata contains coumarin compounds, which possess properties of analgesic and anti-inflammatory effects. In this study, we investigated the therapeutic effect of daphnetin on anti-arthritis and its role on the balance of Tregs and Th17, using a collagen-induced arthritis rat model. Collagen-induced arthritis rats were treated with daphnetin for 21 days. The therapeutic effects of daphnetin were evaluated by clinical symptoms and histopathology. The levels of Th17-, Treg-, Th2-, Th1-type cytokines in serum were determined by ELISA. The expression levels of related receptors RORγt, NF-κB, Foxp3 and CD77 in joint tissues were detected by immunohistochemistry. Our results showed that administration of daphnetin significantly alleviated the severity of the arthritis, as evidenced by the reduction of arthritis scores, suppression of the infiltration of inflammatory cells and prevention of synovial hyperplasia, thereby resulting in the joint destruction in the arthritis rats. Additionally, daphnetin treatment reduced the serum level of Th17-, Th2- and Th1-type in collagen-induced arthritis rats. Correspondingly, the expression of RORγt, NF-κB and CD77 in joint tissue of collagen-induced arthritis rats was remarkably decreased, while the expression of Foxp3 and IL-10 was remarkably increased after being administered with daphnetin. Collectively, this study demonstrated that administration of daphnetin attenuated the clinical symptoms and pathological destruction of arthritis joints. The therapeutic effects were associated with the up-regulation of Tregs, down-regulation of Th17-, Th2- and Th1-type cell responses. The results provide novel evidence that daphnetin has therapeutic effects on autoimmune arthritis through modulating the balance of Tregs and Th17.

• Authors: Rongfeng Yao, Yingyuan Fu, Sha Li, Lina Tu, Xiaoping Zeng, Nanzhen Kuang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 670 Issue 1 Pg. 286-94 (Nov 16 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21914445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Collagen Type II
• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, rat
• NF-kappa B
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Trihexosylceramides
• Umbelliferones
• globotriaosylceramide
• daphnetin

Topics

• Animals
• Arthritis, Experimental (drug therapy, immunology, metabolism)
• Autoimmune Diseases (drug therapy, immunology, metabolism)
• Cattle
• Collagen Type II (adverse effects)
• Cytokines (metabolism)
• Daphne (chemistry)
• Disease Progression
• Down-Regulation (drug effects)
• Female
• Forkhead Transcription Factors (metabolism)
• Inflammation (drug therapy, immunology, metabolism)
• NF-kappa B (metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• Rats
• Rats, Wistar
• T-Lymphocytes, Regulatory (drug effects, metabolism)
• Th1 Cells (drug effects, metabolism)
• Th17 Cells (drug effects, metabolism)
• Th2 Cells (drug effects, metabolism)
• Trihexosylceramides (metabolism)
• Umbelliferones (isolation & purification, pharmacology, therapeutic use)
• Up-Regulation (drug effects)