ReferenceID 1731

Daphnetin inhibits corneal inflammation and neovascularization on a mouse model of corneal alkali burn

Int Immunopharmacol

Alkali burn is a significant contributor to corneal injury. Alkali burn-induced corneal inflammation often causes vision loss due to corneal neovascularization. Daphnetin (DAP) has been studied for its anti-inflammatory

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Reference Id
1731
Evidence Id
18321
Core Evidence Id
18321
Source Reference Id
3442
Herb2 Reference Id
HBREF004239
Subject Paper Key
HBIN022677_34920334
Pubmed Id
34920334
Doi
10.1016/j.intimp.2021.108434
Paper Title
Daphnetin inhibits corneal inflammation and neovascularization on a mouse model of corneal alkali burn
Paper Abstract
Alkali burn is a significant contributor to corneal injury. Alkali burn-induced corneal inflammation often causes vision loss due to corneal neovascularization. Daphnetin (DAP) has been studied for its anti-inflammatory and antiangiogenic properties with encouraging results. Driven by those encouraging results, we sought to explore the effects of DAP in treating alkali burn-induced corneal inflammation and neovascularization and its mechanism of action. We found that the angiogenesis processes of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor A (VEGF-A) were primarily attenuated by treatment with DAP, including proliferation, migration, and tube formation. Treatment of DAP significantly suppressed the VEGF-A-induced protein expression of VEGF receptor2 (VEGFR2), as well as the activation of downstream signal transducer and activator of transcription 3 (STAT3), AKT, and extracellular signal-regulated kinase (ERK) signaling. In the mouse corneal alkali burn model, the inflammatory cell infiltrations and neovascularization in the cornea caused by alkali burn were inhibited by 10 µM DAP eye drops. Alkali burn-induced corneal protein expression of VEGF-A, VEGFR2, phosphorylated (p-)STAT3, p-AKT, and p-ERK in corneal tissue were reduced mainly by DAP. Moreover, the upregulation of inflammatory caused by alkali burn in the pathological process was significantly neutralized by DAP. Mechanistically, the inflammatory response could be alleviated by DAP in the way of inhibiting the expression levels of TLR4, p-NF-κB, NLRP3, ASC, Cleaved-caspase-1 (p20), mature-IL-1β (p17), and N-GSDM. In conclusion, our findings confirmed that the corneal inflammation and neovascularization caused by alkali burn could be inhibited by DAP in vitro and in vivo, elucidating the underlying mechanisms of its protective effects. DAP may have tremendous therapeutic potential for the treatment of corneal alkali burn.
Journal
Int Immunopharmacol
Publish Year
2021
Experiment Subject
mouse; human; huvecs
Experiment Type
Cell Experiment
Phenotype Related
Corneal Neovascularization; Alkali Burn-induced Corneal Inflammation; Corneal Inflammation; Neovascularization; Corneal Alkali Burn; Alkali Burn; Corneal Injury; Vision Loss
Paper Title Cn
Paper Title En
Daphnetin inhibits corneal inflammation and neovascularization on a mouse model of corneal alkali burn
Bilingual Status
semi_complete