Protective Effects of Chlorogenic Acid on Cerebral lschemia/Reperfusion Injury Rats by Regulating Oxidative Stress-Related Nrf2 Pathway

被引：144
作者：
Liu, Dequan [1 ]
Wang, Huilin [1 ]
Zhang, Yangang [2 ]
Zhang, Zhan [2 ]
机构：
[1] Zhengzhou Univ, Luoyang Cent Hosp, Dept Neurol, Luoyang 471000, Henan, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Childrens Hosp, Dept Ultrasound, Xian 710003, Shaanxi, Peoples R China
来源：
DRUG DESIGN DEVELOPMENT AND THERAPY | 2020年 / 14卷
关键词：
cerebral ischemia/reperfusion injury; chlorogenic acid; oxidative stress; neuroprotection; NF-E2-related factor 2 pathway; ISCHEMIA; ACTIVATION; STROKE; ROLES; BRAIN; CELLS;
D O I：
10.2147/DDDT.S228751
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Introduction: Cerebral ischemia-reperfusion (CI/R) injury is caused by blood flow recovery after ischemic stroke. Chlorogenic acid (CGA, 5-O-caffeoylquinic acid) is a major polyphenol component of Coffea canephora, Coffea arabica L. and Mate (Ilex paraguariensis A. StHil.). Previous studies have shown that CGA has a significant neuroprotective effect and can improve global CI/R injury. However, the underlying molecular mechanism of CGA in CI/R injury has not been fully revealed. Materials: In this study, CI/R rat model was constructed. The rats were randomly divided into nine groups with ten in each group: Control, CGA (500 mg.kg-1), CI/R, CI/R + CGA (20 mg.kg-1), CI/R + CGA (100 mg.kg-1), CI/R + CGA (500 mg.kg-1), ML385 (30 mg.kg-1), CI/R + ML385 (30 mg.kg-1), CI/R + CGA + ML385. Cerebral infarction volume was detected by TTC staining. Brain pathological damage was detected by H&E staining. Apoptosis of cortical cells was detected by TUNEL staining. The expression of related proteins was detected by RT-qPCR and Western blotting. Results: Step-down test and Y maze test showed that CGA dose-dependently mitigated CI/R-induced brain damage and enhanced learning and spatial memory. Besides, CGA promoted the expression of BDNF and NGF in a dose-dependent manner and alleviated CI/R-induced nerve injury. Moreover, CGA increased the activity of SOD and the level of GSH, as well as decreased production of ROS and LDH and the accumulation of MDA. Notably, CGA attenuated oxidative stress-induced brain injury and apoptosis and inhibited the expression of apoptosis-related proteins (cleaved caspase 3 and caspase 9). Additionally, CGA reversed CI/R induced inactivation of Nrf2 pathway and promoted Nrf2, NQO-1 and HO-1 expression. Nrf2 pathway inhibitor ML385 destroyed this promotion. Discussion: All the data indicated that CGA had a neuroprotective effect on the CI/R rats by regulating oxidative stress-related Nrf2 pathway.
引用
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页码：51 / 60
页数：10
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