Daphnetin Alleviates Experimental Autoimmune Encephalomyelitis via Regulating Dendritic Cell Activity

Wang, Dan; Lü, Zhe; Zhang, Hang; Jin, Sufeng; Yang, Hao; Li, Yunman; Shi, Liyun

doi:10.1111/cns.12537

Cited by 17 publications

(17 citation statements)

References 61 publications

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“…Daphnetin (DAPH; 7, 8-dihydroxycoumarin) is a coumarin derivative extracted from Daphne odora var. marginata, known to have robust anti-inflammatory and antioxidative properties that is widely used in treating inflammatory diseases (21)(22)(23). Our previous study showed that DAPH alleviated experimental autoimmune encephalomyelitis by regulating dendritic cell activity (22).…”

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confidence: 99%

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance

Chen

et al. 2019

FASEB j.

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Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti‐inflammatory and immune‐regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium–treated mice. In particular, this agent significantly elevated the abundance of short‐chain fatty acid (SCFA)–producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA‐producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.—Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance. FASEB J. 33,9308–9322 (2019). http://www.fasebj.org

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confidence: 99%

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance

Chen

et al. 2019

FASEB j.

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“…In addition, 10 mg/kg and 20 mg/kg of DAP protected against cerebral I/R injury to the same degree in this model ( P > 0.05). Based on these results and the previous study [14, 15], the optimal treatment dose of DAP (10 mg/kg) was used in the following experiment.…”

Section: Resultsmentioning

confidence: 97%

“…10 mg/kg and 20 mg/kg of DAP protected against cerebral I/R injury to the same degree, whereas 5 mg/kg of DAP did not show neuroprotective effects. According to this result and the previous study [14, 15], 10 mg/kg was chosen as the optimal treatment dose in the subsequent experiment.…”

Section: Discussionmentioning

confidence: 93%

“…DAP inhibits the infiltration of inflammatory cells and alleviates the inflammatory injury state in mice through decreasing the production of proinflammatory cytokines, including tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), and interleukin-6 (IL-6) [10–12]. More importantly, novel findings suggested that DAP had neuroprotective effects in experimental autoimmune encephalomyelitis [14] and prevented chronic unpredictable stress-induced cognitive deficits [15]. However, the neuroprotective effect of DAP on cerebral I/R injury is not yet clear and the ability of DAP to antagonize the inflammatory signaling pathway in brain remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway

Liu

Chen

Jian

et al. 2016

BioMed Research International

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Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R injury is not yet clear. Recent studies have demonstrated that TLR4/NF-κB signaling pathway takes part in the damaging inflammatory process of cerebral I/R injury. The present study aimed to investigate the effect of DAP on cerebral I/R injury in vivo and its possible mechanisms. DAP was administered before middle cerebral artery occlusion and reperfusion in mice. The neurological scores, cerebral infarct sizes, the levels of inflammatory cytokines, apoptotic neural cells, and the levels of TLR4, NF-κB p65, and IκBα were estimated. The results showed that an obvious improvement of neurological scores and infarct sizes was observed in DAP-treated mice after MCAO/R. DAP treatment decreased the overexpression of TNF-α, IL-1β, and IL-6 and attenuated neural cells apoptosis. Moreover, DAP treatment decreased the TLR4 expression, IκB-α degradation, and nuclear translocation of NF-κB. Taken together, our results suggested that DAP exerted neuroprotective and anti-inflammatory effects on cerebral I/R injury. The potential mechanism was involved in the inhibition of TLR4/NF-κB mediated inflammatory signaling pathway.

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“…Subsequently, DAP was found to prevent and treat numerous diseases, including cerebral ischaemia/reperfusion injury, rheumatoid arthritis, colitis and endotoxin-induced lung injury, due to its powerful anti-inflammatory activities (24,(27)(28)(29)(30)(31)(32). At present, DAP is an anti-inflammatory agent used in some inflammation-related diseases (33)(34)(35). Li et al (33) reported that DAP inhibited inflammation in the systemic lupus erythematosus murine model via inhibition of NF-κB activity.…”

Section: Introductionmentioning

confidence: 99%

Daphnetin suppresses experimental abdominal aortic aneurysms in mice via inhibition of aortic mural inflammation

Xie

Guan

et al. 2020

Exp Ther Med

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Rupture of abdominal aortic aneurysm (AAA) is a devastating event that can be prevented by inhibiting the growth of small aneurysms. Therapeutic strategies targeting certain events that promote the development of AAA must be developed, in order to alter the course of AAA. Chronic inflammation of the aortic mural is a major characteristic of AAA and is related to AAA formation, development and rupture. Daphnetin (DAP) is a coumarin derivative with anti-inflammatory properties that is extracted from Daphne odora var. However, the effect of DAP on AAA development remains unclear. The present study investigated the effect of DAP on the formation and development of experimental AAAs and its potential underlying mechanisms. A mice AAA model was established by intra-aortic infusion of porcine pancreatic elastase (PPE), and mice were intraperitoneally injected with DAP immediately after PPE infusion. The maximum diameter of the abdominal aorta was measured by ultrasound system, and aortic mural changes were investigated by Elastica van Gieson (EVG) staining and immunohistochemical staining. The results demonstrated that DAP significantly suppressed PPE-induced AAA formation and attenuated the depletion of aortic medial elastin and smooth muscle cells in the media of the aorta. Furthermore, the density of mural macrophages, T cells and B cells were significantly attenuated in DAP-treated AAA mice. In addition, treatment with DAP resulted in a significant reduction in mural neovessels. These findings indicated that DAP may limit the formation and progression of experimental aneurysms by inhibiting mural inflammation and angiogenesis. These data confirmed the translational potential of DAP inclinical AAA inhibition strategies.

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Daphnetin Alleviates Experimental Autoimmune Encephalomyelitis via Regulating Dendritic Cell Activity

Abstract: Our findings for the first time demonstrate the property of daphnetin in regulating DCs' function and subsequently Th development. Given the low or absent toxicity associated with daphnetin, our data may suggest a novel safe and effective approach to control autoimmune neuroinflammation.

Cited by 17 publications

References 61 publications

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance

Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway

Daphnetin suppresses experimental abdominal aortic aneurysms in mice via inhibition of aortic mural inflammation

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Daphnetin Alleviates Experimental Autoimmune Encephalomyelitis via Regulating Dendritic Cell Activity

Abstract: Our findings for the first time demonstrate the property of daphnetin in regulating DCs' function and subsequently Th development. Given the low or absent toxicity associated with daphnetin, our data may suggest a novel safe and effective approach to control autoimmune neuroinflammation.

Cited by 17 publications

References 61 publications

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T reg /T h 17 balance

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T reg /T h 17 balance

Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway

Daphnetin suppresses experimental abdominal aortic aneurysms in mice via inhibition of aortic mural inflammation

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Product

Resources

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Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance

Daphnetin ameliorates experimental colitis by modulating microbiota composition and T _reg /T _h 17 balance