4.6

CiteScore

2.2

Impact Factor
  • ISSN 1674-8301
  • CN 32-1810/R
Huanyu Ni, Yixuan Song, Haiyin Wu, Lei Chang, Chunxia Luo, Dongya Zhu. 2-Methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine, an edaravone analog, exerts neuroprotective effects against acute ischemic injury via inhibiting oxidative stress[J]. The Journal of Biomedical Research, 2018, 32(4): 270-280. DOI: 10.7555/JBR.32.20180014
Citation: Huanyu Ni, Yixuan Song, Haiyin Wu, Lei Chang, Chunxia Luo, Dongya Zhu. 2-Methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine, an edaravone analog, exerts neuroprotective effects against acute ischemic injury via inhibiting oxidative stress[J]. The Journal of Biomedical Research, 2018, 32(4): 270-280. DOI: 10.7555/JBR.32.20180014

2-Methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine, an edaravone analog, exerts neuroprotective effects against acute ischemic injury via inhibiting oxidative stress

Funds: 

This work was supported by grants from National Natural Science Foundation of China (31530091,91232304), National Key Research and Development Program of China (2016YFC1306703) and Natural Science Foundation of Jiangsu Province (BK20140905),and by the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine. We thank Nanjing Zhongrui Pharmaceutical Co., Ltd. for the technical assistance.

More Information
  • Received Date: January 31, 2018
  • Revised Date: March 12, 2018
  • Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia. Inhibiting oxidative stress has been considered as an effective approach for stroke treatment. Edaravone, a free radical scavenger, has been shown to prevent cerebral ischemic injury. However, the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions (O2$–). Here, we report that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3] oxazin-5-imine, a novel small-molecule compound structurally related to edaravone, showed a stronger inhibitory effect on oxidative stress in vitro. In vivo, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde, two proteins crucial for oxidative stress,suggesting a strengthened antioxidant system. Moreover, 2-methyl-5H-benzo[d] pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability. Then, we found that 2-methyl-5Hbenzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone. More importantly, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period, indicating enhanced neuroprotection, sensorimotor function and spatial memory. Together, thesevfindings suggest that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.
  • Related Articles

    [1]Zhaoye Qian, Zhe Zhang, Lanqi Cen, Yaohua Ke, Jie Shao, Manman Tian, Baorui Liu. Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy[J]. The Journal of Biomedical Research, 2024, 38(4): 369-381. DOI: 10.7555/JBR.38.20240049
    [2]Lulu Fan, Hao Wang, Shuai Ben, Yifei Cheng, Silu Chen, Zhutao Ding, Lingyan Zhao, Shuwei Li, Meilin Wang, Gong Cheng. Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression[J]. The Journal of Biomedical Research, 2024, 38(2): 149-162. DOI: 10.7555/JBR.37.20230049
    [3]Cui Qi, Jiaqi Zhang, Yuanyuan Wang, Mingyan Lin, Jun Gao, Haiying Lu. Valproic acid enhances neurosphere formation in cultured rat embryonic cortical cells through TGFβ1 signaling[J]. The Journal of Biomedical Research, 2022, 36(2): 127-140. DOI: 10.7555/JBR.36.20210109
    [4]Xu Wenbin, Yan Han, Xu Lulu, Li Mingna, Gao Wentao, Jiang Kuirong, Wu Junli, Miao Yi. Correlation between radiologic features on contrast-enhanced CT and pathological tumor grades in pancreatic neuroendocrine neoplasms[J]. The Journal of Biomedical Research, 2021, 35(3): 179-188. DOI: 10.7555/JBR.34.20200039
    [5]Yang Lukun, Tautz Timothy, Zhang Shulin, Fomina Alla, Liu Hong. The current status of malignant hyperthermia[J]. The Journal of Biomedical Research, 2020, 34(2): 75-85. DOI: 10.7555/JBR.33.20180089
    [6]Huanqiang Wang, Congying Yang, Siyuan Wang, Tian Wang, Jingling Han, Kai Wei, Fucun Liu, Jida Xu, Xianzhen Peng, Jianming Wang. Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer[J]. The Journal of Biomedical Research, 2018, 32(6): 424-433. DOI: 10.7555/JBR.32.20170065
    [7]Cuiying Li, Haiyan Gong, Lijun Ling, Liwen Du, Tong Su, Shui Wang, Jie Wang. Diagnostic performance of contrast-enhanced ultrasound and enhanced magnetic resonance for breast nodules[J]. The Journal of Biomedical Research, 2018, 32(3): 198-207. DOI: 10.7555/JBR.32.20180015
    [8]Nolan B. Ayers, Chenming Sun, Shi-You Chen. Transforming growth factor-β signaling in systemic sclerosis[J]. The Journal of Biomedical Research, 2018, 32(1): 3-12. DOI: 10.7555/JBR.31.20170034
    [9]Jun Han, Chuanbing Shi, Xiaogang Dong, Jie Wang, Hao Wen, Baolin Wang, Zhenyu He. Laparoscopic abdomino-perineal resection for patients with anorectal malignant melanoma: a report of 4 cases[J]. The Journal of Biomedical Research, 2016, 30(5): 436-440. DOI: 10.7555/JBR.27.20120099
    [10]Subhasree Nag, Jiangjiang Qin, Kalkunte S. Srivenugopal, Minghai Wang, Ruiwen Zhang. The MDM2-p53 pathway revisited[J]. The Journal of Biomedical Research, 2013, 27(4): 254-271. DOI: 10.7555/JBR.27.20130030
  • Cited by

    Periodical cited type(5)

    1. Langyan S, Bhardwaj R, Kumari J, et al. Nutritional Diversity in Native Germplasm of Maize Collected From Three Different Fragile Ecosystems of India. Front Nutr, 2022, 9: 812599. DOI:10.3389/fnut.2022.812599
    2. Juvinao-Quintero DL, Cardenas A, Perron P, et al. Associations between an integrated component of maternal glycemic regulation in pregnancy and cord blood DNA methylation. Epigenomics, 2021, 13(18): 1459-1472. DOI:10.2217/epi-2021-0220
    3. Zhang J, Wu X. Predict Health Care Accessibility for Texas Medicaid Gap. Healthcare (Basel), 2021, 9(9): 1214. DOI:10.3390/healthcare9091214
    4. Ayati M, Koyutürk M. PoCos: Population Covering Locus Sets for Risk Assessment in Complex Diseases. PLoS Comput Biol, 2016, 12(11): e1005195. DOI:10.1371/journal.pcbi.1005195
    5. Zhang Q, Zhao Y, Zhang R, et al. A Comparative Study of Five Association Tests Based on CpG Set for Epigenome-Wide Association Studies. PLoS One, 2016, 11(6): e0156895. DOI:10.1371/journal.pone.0156895

    Other cited types(0)

Catalog

    Article Metrics

    Article views (3616) PDF downloads (174) Cited by(5)
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return