Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO‐1 signaling pathway in mice

Xu, Lili; Gao, Yaran; Hu, Ming; Dong, Yanhong; Xu, Jing; Zhang, Jiawei; Lv, Peiyuan

doi:10.1111/fcp.12782

Cited by 27 publications

(9 citation statements)

References 60 publications

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“…Neuroinflammation is one of the key factors of I/R injury, which has a profound impact on the prognosis of cerebral I/R. It is worth noting that C.EDA can reduce the levels of inflammatory factors and free radicals, and protect neurons in the models of cerebral ischemia and post‐stroke depression (Xu et al, 2022; Yajie Zhang et al, 2022). However, the specific function and anti‐inflammatory mechanism of C.EDA in I/R injury is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Edaravone dexborneol alleviates cerebral ischemia‐reperfusion injury through NF‐κB/NLRP3 signal pathway

Shen

Lou

et al. 2023

The Anatomical Record

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Inflammatory injury following ischemia‐reperfusion (I/R) severely limits the efficacy of stroke treatment. Edaravone dexborneol (C.EDA) has been shown to reduce inflammation following a cerebral hemorrhage. However, the precise anti‐inflammatory mechanism of C.EDA is unknown. In this study, we investigated whether C.EDA provides neuroprotection after I/R in rats, as well as the potential mechanisms involved. A middle cerebral artery occlusion/reperfusion (I/R) model was created using Sprague‐Dawley rats. The blood flow of the central cerebral artery was monitored by a laser speckle imaging system. The neurological score was used to assess behavioral improvement. Cerebral infarction volume was measured by TTC staining. And the integrity of the blood–brain barrier was detected by Evan's blue staining. The expression of the nuclear factor kappa‐B (NF‐κB)/ the NOD‐like receptor protein (NLRP3) inflammasome signal pathway and microglia polarization were detected by immunofluorescence and Western blotting. The cerebral blood flow ratio indicates that the cerebral I/R model was successfully established. After reperfusion for 72 h, the improvement of neurological scores, infarct volume reduction, and integrity of the blood–brain barrier was observed in I/R rats with C.EDA treatment. Meanwhile, the immunofluorescence result showed that the expression of iNOS, NLRP3, and NF‐κB protein was decreased and the level of Arg1 was increased. Western blot analysis showed that the expression of NF‐κB/NLRP3 signal pathway‐related protein was decreased. In conclusion, this study indicates that C.EDA alleviates I/R injury by blocking the activation of the NLRP3 inflammasome and regulating the polarization of M1/M2 microglia via the NF‐κB signal pathway.

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Section: Discussionmentioning

confidence: 99%

Edaravone dexborneol alleviates cerebral ischemia‐reperfusion injury through NF‐κB/NLRP3 signal pathway

Shen

Lou

et al. 2023

The Anatomical Record

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“…For stroke, it was revealed that Eda.B could scavenge free radicals, decrease infarct area, and inhibit proinflammatory mediator expression in rats [ 14 ]. After 2020, more researches about Eda.B on stroke and subarachnoid hemorrhage were conducted [ 21 , 22 ]. These studies still focused on the anti-inflammatory effects of Eda.B.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study demonstrated that Eda.B could promote M2 macrophage polarization via the JAK2-STAT3 signaling pathway [ 15 ]. A recently published study pointed that Eda.B could stimulate the Nrf2/HO-1 pathway to inhibit NADPH oxidase 2 expression in mice after stroke [ 22 ]. Considering the relative mechanism of NET production, the apoptotic pathways may play an important role in the pharmacological effect of Eda.B.…”

Section: Discussionmentioning

confidence: 99%

Edaravone Dexborneol Downregulates Neutrophil Extracellular Trap Expression and Ameliorates Blood-Brain Barrier Permeability in Acute Ischemic Stroke

Huang

Zhang

et al. 2022

Mediators of Inflammation

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Background. Our previous work has shown that inflammatory processes play a detrimental role in the pathophysiology of acute ischemic stroke (AIS). Neutrophil extracellular traps (NETs) have been recognized as a key contributor to the proinflammatory response in AIS and could aggravate blood-brain barrier (BBB) damage. Recently, experimental and clinical researches showed that Edaravone Dexborneol (Eda.B), which is comprised of two active ingredients, Edaravone and (+)-Borneol, was effective in treatment of AIS. However, it is not clear whether the effects of Eda.B against AIS are related to NETs and BBB permeability. Methods. Experiment 1 was to detect the effects of Eda.B in AIS patients. Serum samples of volunteers and AIS patients were collected before and 3 days after Edaravone Dexborneol treatment. Markers of NETs and occludin were detected by ELISA kit. Experiment 2 was to explore the effects of Eda.B on experimental stroke mice. Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (MCAO) and treated with vehicle, Eda.B, or DeoxyribonueleaseI (DNase I). After stroke, the neurobehavioral tests, infarct volume, and cerebral blood flow evaluation were determined. Leakage of Evans blue was to assess the integrity of BBB. Western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence were used to examine the expression of NETs and tight junction- (TJ-) associated proteins. Results. Eda.B significantly improved neurological function and cerebral blood flow but reduced infarct volume after experimental stroke. Eda.B downregulated level of NETs in serum samples of AIS patients and tissue samples of MCAO mouse cortex. Eda.B and DNase I alleviated BBB permeability by upregulating TJ-associated proteins. Conclusion. NETs are related to the early stage of AIS. Eda.B exerted neuroprotective effects and ameliorated BBB permeability after AIS.

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“…The American Heart/Stroke Association’s journal Stroke published the results of China’s ED phase III trial online ( Xu et al, 2021 ). It was found that ED can protect hippocampal HT22 neurons, astrocytes, and vascular endothelial cells under stress, indicating that it can protect the entire neurovascular unit and inhibit neural apoptosis ( Lee et al, 2010 ; Chen et al, 2022 ; Xu et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction

Liu

Liu²,

Wei³

et al. 2023

Front. Neurosci.

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ObjectiveThis study aimed to investigate the effect of Edaravone Dexborneol (ED) on impaired learning and memory in docetaxel (DTX)-treated rats using cognitive behavior assessments and magnetic resonance diffusion tensor imaging (DTI).Materials and methodsIn total, 24 male Sprague–Dawley rats were divided into control, low-dose DTX (L-DTX) model, and high-dose DTX(H-DTX) model groups, with eight rats in each group, numbered 1–8. The rats were intraperitoneally injected with 1.5 mL of either normal saline (control group), or 3 mg/kg and 6 mg/kg DTX (L-DTX and H-DTX groups, respectively), once a week for 4 weeks. The learning and memory abilities of each group were tested using a water maze. At the end of the water maze test, rats 1–4 in each group were treated with ED (3 mg/kg, 1 mL), and rats 5–8 were injected with an equal volume of normal saline once a day for 2 weeks. The learning and memory abilities of each group were evaluated again using the water maze test, and the image differences in the hippocampus of each group were analyzed using DTI.Results(1) H-DTX group (32.33 ± 7.83) had the longest escape latency, followed by the L-DTX group (27.49 ± 7.32), and the Control group (24.52 ± 8.11) having the shortest, with the difference being statistically significant (p < 0.05). (2) Following ED treatment, compared to rats treated with normal saline, the escape latency of the L-DTX (12.00 ± 2.79 vs. 10.77 ± 3.97, p < 0.05), and the H-DTX (12.52 ± 3.69 vs. 9.11 ± 2.88, p < 0.05) rats were significantly shortened. The residence time in the target quadrant of H-DTX rats was significantly prolonged (40.49 ± 5.82 vs. 55.25 ± 6.78, p < 0.05). The CNS damage in the L-DTX rats was repaired to a certain extent during the interval between the two water maze tests (28.89 ± 7.92 vs. 12.00 ± 2.79, p < 0.05). (3) The fractional anisotropy (FA) value of DTI in the hippocampus of rats in the different groups showed variable trends. After treatment with ED, though the FA values of most areas in the hippocampus of rats in L-DTX and H-DTX groups were higher than before, they did not reach the normal level.ConclusionED can ameliorate the cognitive dysfunctions caused by DTX in rats by improving the learning and memory impairment, which is reflected in the recovery of biological behavior and DTI indicators of the hippocampus.

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Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO‐1 signaling pathway in mice

Cited by 27 publications

References 60 publications

Edaravone dexborneol alleviates cerebral ischemia‐reperfusion injury through NF‐κB/NLRP3 signal pathway

Edaravone dexborneol alleviates cerebral ischemia‐reperfusion injury through NF‐κB/NLRP3 signal pathway

Edaravone Dexborneol Downregulates Neutrophil Extracellular Trap Expression and Ameliorates Blood-Brain Barrier Permeability in Acute Ischemic Stroke

Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction

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