Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis
Shao, CW (Shao, Chenwen)[ 1,2 ] ; Yuan, JW (Yuan, Jiwen)[ 2 ] ; Liu, YN (Liu, Yani)[ 2 ] ; Qin, YJ (Qin, Yajuan)[ 3 ] ; Wang, XA (Wang, Xueao)[ 2 ] ; Gu, J (Gu, Jin)[ 2 ] ; Chen, GQ (Chen, Guiquan)[ 4 ] ; Zhang, B (Zhang, Bing)[ 5 ] ; Liu, HK (Liu, Hong-Ke)[ 1 ] ; Zhao, J (Zhao, Jing)[ 2 ]*; Zhu, HL (Zhu, Hai-Liang)[ 2 ]*; Qian, Y (Qian, Yong)[ 1,2 ]*（钱勇）

[ 1 ] Nanjing Normal Univ, Sch Chem & Mat Sci, Nanjing 210046, Peoples R China
[ 2 ] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China
[ 3 ] Nanjing Med Univ, Sch Pharm, Nanjing 211166, Peoples R China
[ 4 ] Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing 210061, Peoples R China
[ 5 ] Nanjing Univ, Dept Radiol, Sch Med, Affiliated Drum Tower Hosp, Nanjing 210008, Peoples R China

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,202005,117(19),10155-10164

Myeloperoxidase (MPO)-mediated oxidative stress has been suggested to play an important role in the pathological dysfunction of epileptic brains. However, there is currently no robust brain-imaging tool to detect real-time endogenous hypochlorite (HClO) generation by MPO or a fluorescent probe for rapid high-throughput screening of antiepileptic agents that control the MPO-mediated chlorination stress. Herein, we report an efficient two-photon fluorescence probe (named HCP) for the real-time detection of endogenous HClO signals generated by MPO in the brain of kainic acid (KA)-induced epileptic mice, where HClO-dependent chlorination of quinolone fluorophore gives the enhanced fluorescence response. With this probe, we visualized directly the endogenous HClO fluxes generated by the overexpression of MPO activity in vivo and ex vivo in mouse brains with epileptic behaviors. Notably, by using HCP, we have also constructed a high-throughput screening approach to rapidly screen the potential antiepileptic agents to control MPO-mediated oxidative stress. Moreover, from this screen, we identified that the flavonoid compound apigenin can relieve the MPO-mediated oxidative stress and inhibit the ferroptosis of neuronal cells. Overall, this work provides a versatile fluorescence tool for elucidating the role of HClO generation by MPO in the pathology of epileptic seizures and for rapidly discovering additional antiepileptic agents to prevent and treat epilepsy.

文章链接：
https://www.pnas.org/content/117/19/10155

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