Research Papers: Neuroscience:

5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury

Jia Zhou _, Yi-hua Zhang, Hui-zhu Song, Hui Ji, Xiao-li Wang, Lei Wang, Jun Qian, Jing-jing Ling and Feng-feng Ping

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Oncotarget. 2016; 7:39444-39457. https://doi.org/10.18632/oncotarget.8548

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Jia Zhou1,*, Yi-hua Zhang2,*, Hui-zhu Song3, Hui Ji2, Xiao-li Wang1, Lei Wang3, Jun Qian3, Jing-jing Ling3 and Feng-feng Ping3

1 School of Pharmaceutical Science, Jiangnan University, Wuxi, P.R. China

2 State Key Laboratory of Natural Medicines, Center of Drug discovery, China Pharmaceutical University, Nanjing, P.R. China

3 Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, P.R. China

* These authors have contributed equally to this work

Correspondence to:

Jing-jing Ling, email:

Feng-feng Ping, email:

Keywords: 5d; neuroprotection; CK2; NADPH oxidase; ROS; Neuroscience

Received: December 07, 2015 Accepted: May 05, 2016 Published: May 12, 2016


5d, a novel analogue of the racemic 3-n-butylphthalide (NBP), has been reported for its free radical scavenging activity in vitro and preventive neuroprotection in vivo. Nevertheless, the mechanism by which 5d attenuated ischemia/reperfusion (I/R) injury is still unknown. Our results showed that 5d significantly increased CK2 activity as well as CK2α and 2α’ protein levels after I/R injury. Besides, 5d suppressed the translocation of cytosolic p47phox and Rac1 to the membrane, decreased NOX4 expression and ROS generation. Furthermore, 5d blocked the dissociation between CK2α and Rac1 so as to decrease NADPH oxidase activity. Based on these findings, we propose that the neuroprotective effect of 5d is due to an increase of CK2 activity, which blocks I/R-induced dissociation between CK2α and Rac1, decreases NADPH oxidase activity, inhibits ROS production and finally realizes the neuroprotection of I/R. These findings point to that 5d might be considered an attractive candidate for further studies in ischemic stroke.

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