Article

The therapeutic effects of daphnetin in collagen-induced arthritis involve its regulation of Th17 cells.

Department of Immunology, Medical College of Nanchang University, 461 Nanchang Bayi Road, Nanchang of Jiangxi Province 330006, China.
International immunopharmacology (Impact Factor: 2.21). 04/2012; 13(4):417-23. DOI: 10.1016/j.intimp.2012.04.001
Source: PubMed

ABSTRACT Daphne odora var. marginata (D. marginata), an aiophyllus arbuscular plant, is one of the traditional Chinese medicines used to treat rheumatoid arthritis. This study investigated the therapeutic effects and mechanisms of daphnetin, an active monomer ingredient derived from D. marginata, on collagen-induced arthritis (CIA) in rats.
The effects of daphnetin on joint diseases were assessed by hematoxylin and eosin staining and radiographic and transmission electron microscopy. The protein and mRNA expression levels of T helper (Th)1/Th2/Th17-type cytokines in the spleen were determined by flow cytometry and quantitative real-time PCR.
Our results showed that daphnetin significantly reduced paw swelling and was nontoxic in vivo at the tested doses. Synovial hyperplasia, joint destruction and chondrocyte degeneration in CIA rats were suppressed by daphnetin. Daphnetin treatment also reduced the levels of Th1/Th2/Th17 type cytokines in spleen lymphocytes in CIA rats. Moreover, the expression of Foxp3, which can down-regulate the activity of Th17 cells, was significantly increased in the daphnetin-treated groups.
These results suggest that daphnetin may have therapeutic effects in down-regulating Th17-type responses in CIA rats. The beneficial effects of daphnetin on CIA may be related to its inhibition of Th17 cell priming and activation.

0 Bookmarks
 · 
60 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke.
    Neurochemical Research 12/2013; · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Daphnetin, a natural coumarin derivative, is known to display anti-inflammatory properties and has been used to treat inflammatory diseases. A novel finding suggested that daphnetin might have a neuroprotective effect in stressed mice, leading us to explore its role in the microglial inflammatory response, as well as its underlying mechanism of action. We found that the production of pro-inflammatory mediators, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), induced by lipopolysaccharide (LPS) or β-amyloid (Aβ) was significantly suppressed by daphnetin in a dose-dependent manner in BV2 microglia. Also, daphnetin inhibited LPS-induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and NO formation by microglia. Mechanistically, daphnetin blunted the transcriptional activity of nuclear factor-kappa B (NF-κB), which was associated with the down-regulation of the phosphorylation and nuclear translocation of RelA/p65. Inhibitors of kappa B (IκB) phosphorylation and degradation were also affected by daphnetin, which was likely due to the reduced activation of IκB kinase (IKK). Additionally, LPS-induced activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK, were, to a varying extent, altered by daphnetin. Finally, daphnetin blocked phosphatidylinositol-3 kinase (PI-3K)/protein kinase B (Akt) signaling in LPS-activated microglia, which appeared to at least partially account for the reduction in NF-κB transcriptional activity. Thus, daphnetin inhibited microglial activation and proinflammatory responses by modulating a series of intracellular signaling pathways, including IKK/IκB, MAPKs and PI-3K/Akt.
    International immunopharmacology 04/2014; · 2.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Daphnetin, a plant-derived dihydroxylated derivative of coumarin, is an effective compound extracted from a plant called Daphne Korean Nakai. Coumarin derivates were known for their antithrombotic, anti-inflammatory, and antioxidant activities. The present study was aimed to determine the immunosuppressive effects and the underlying mechanisms of daphnetin on concanavalin A (ConA) induced T lymphocytes in mice. We showed that, in vitro, daphnetin suppressed ConA-induced splenocyte proliferation, influenced production of the cytokines and inhibited cell cycle progression through the G0/G1 transition. The data also revealed that daphnetin could down-regulate activation of ConA induced NF-κB and NFAT signal transduction pathways in mouse T lymphocyte. In vivo, daphnetin treatment significantly inhibited the 2, 4- dinitrofluorobenzene (DNFB) -induced delayed type hypersensitivity (DTH) reactions in mice. Collectively, daphnetin had strong immunosuppressive activity both in vitro and in vivo, suggesting a potential role for daphnetin as an immunosuppressive agent, and established the groundwork for further research on daphnetin.
    PLoS ONE 01/2014; 9(5):e96502. · 3.53 Impact Factor