Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging RO...Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2 O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 couldemerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.展开更多
The authors regret that there was a picture error in Fig.5D and Fig.5E,owing to the authors’mistakes of copying and pasting in the process of assembling figures and making a diagram.In Fig.5D,the image of the edaravo...The authors regret that there was a picture error in Fig.5D and Fig.5E,owing to the authors’mistakes of copying and pasting in the process of assembling figures and making a diagram.In Fig.5D,the image of the edaravone 6 h group(ED-6h group)was repeated with the model group(NS group),and thus the image of the ED-6h group needs to be corrected.In Fig.5E,the data of the edaravone 3h group(ED-3h group)was repeated with the 336h group(33-6h group),and thus the data of the ED-3h group needs to be corrected.展开更多
基金supported by ZheJiang Province Natural Science Funding of China (Nos. LQ18H280008, Y19B020043, and LY17H160059, China)the National Natural Science Foundation of China (No. 81803580, China)+2 种基金University Students in Zhejiang Science and Technology Innovation Projects (No. 2018R413004, China)National Undergraduate Training Programs for Innovation and Entrepreneurship (No. 201810343025, China)Granted by the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences
文摘Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2 O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 couldemerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.
文摘The authors regret that there was a picture error in Fig.5D and Fig.5E,owing to the authors’mistakes of copying and pasting in the process of assembling figures and making a diagram.In Fig.5D,the image of the edaravone 6 h group(ED-6h group)was repeated with the model group(NS group),and thus the image of the ED-6h group needs to be corrected.In Fig.5E,the data of the edaravone 3h group(ED-3h group)was repeated with the 336h group(33-6h group),and thus the data of the ED-3h group needs to be corrected.
