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

Abstract

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.

LncRNA ANRIL protects against oxygen and glucose deprivation (OGD)-induced injury in PC-12 cells: potential role in ischaemic stroke

“…Ischaemic stroke (IS), which accounts for approximately 85% of all strokes is caused by immediate deprivation of both glucose and oxygen caused by the rapid loss in blood flow to brain [1,2]. Accumulating evidence revealed that IS becomes one of the leading cause of mortality and disability in adults all through the world [3]. Nowadays, the therapies for IS are intravenous alteplase administered within 4.5 h after symptom onset and mechanical thrombectomy [4,5].…”

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

“…It has been reported that the TLR4/NF-κB signaling pathway accelerates the inflammatory process in neuroinflammatory injury [39][40][41]. NF-κB is a nuclear transcription factor that regulates the expression of numerous genes that are responsible for regulating apoptosis, tumorigenesis, inflammation, and various autoimmune diseases [42].…”

Daphnetin inhibits RANKL‐induced osteoclastogenesis in vitro

“…Daphnetin is a natural coumarin derivative isolated from the traditional Chinese medicine genus Daphne , which is traditionally used for the treatment of rheumatoid arthritis . Daphnetin has been shown to possess broad bioactivities such as antioxidative, anti‐inflammatory, antitumor, and antiarthritis effects . However, the role of daphnetin in osteoclast formation remains unclear.…”

“…7,8 Daphnetin has been shown to possess broad bioactivities such as antioxidative, anti-inflammatory, antitumor, and antiarthritis effects. [9][10][11][12][13] However, the role of daphnetin in osteoclast formation remains unclear. In this study, we investigated the effects of daphnetin on RANKL-induced osteoclastogenesis using bone marrow-derived macrophages (BMMs).…”