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The relationship between EGCG targeted regulation of Nrf2⁃Keap1 signaling pathway and neuroprotective effect in cerebral infarction
Received date: 2023-07-25
Online published: 2024-02-22
Objective The preventive effect of epigallocatechin gallate （EGCG） on hyperglycemia?induced hemorrhagic transformation （HT） was analyzed， and the underlying mechanisms were further explored. Methods Male SD rats were randomly divided into sham operation group （Sham， n = 20）， model group （n = 27）， hyperglycemia model group （HG， n = 43）， and EGCG group （n = 43）. In the model group， only the electrocoagulation cerebral ischemia model was established， and the HG group and the EGCG group were used to establish the HT model with acute hyperglycemia combined with electrocoagulation cerebral ischemia model. In addition， EGCG was administered by gavage for 5 days before cerebral ischemia at a dose of 50 mg/kg/d. Further studies confirmed the relevant targets by using network pharmacology to predict the potential targets and pathways of EGCG in the occurrence of HT. Results Compared with the model group， the mortality rate of the rats in the HG group was significantly increased ［21.2% （6/27） vs. 51.2% （22/43）， P < 0.05］. The mortality of rats in the EGCG group was significantly lower than that in the HG group ［30.20% （13/43） vs. 51.2% （22/43）， P < 0.05］. Second， mNSS， Longa score and infarct volume in the EGCG group were significantly lower than those in the HG group （P < 0.05）. The incidence of HT in the HG group was higher than that in the model group （59.3% vs. 90.7%）. EGCG significantly reduced the incidence of hyperglycemia?induced HT to 69.8%. Compared with the HG group， EGCG decreased the hemoglobin content from （53.42 ±?5.11） mg/dL to （37.04?±?2.39）?mg/dL respectively （P < 0.05）. Network pharmacology revealed that Nrf2?Keap1?mediated neuroinflammation may be associated with hyperglycemia?induced HT. The expression of Nrf2 and Keap1 was significantly decreased and the expression of TLR4 and phosphorylation of NF?κB was significantly increased in the HG group， but EGCG reversed this process. Conclusion EGCG pretreatment prevents the occurrence of HT， which may be related to the neuroprotection mediated by activation of the Nrf2?Keap1 signaling pathway.
Xiangzhi XIAO , Guanxiong CHEN , Zhiwen HU . The relationship between EGCG targeted regulation of Nrf2⁃Keap1 signaling pathway and neuroprotective effect in cerebral infarction[J]. The Journal of Practical Medicine, 2024 , 40(3) : 309 -315 . DOI: 10.3969/j.issn.1006-5725.2024.03.005
| 1 | SHI K， ZOU M， JIA D M， et al. tPA mobilizes immune cells that exacerbate hemorrhagic transformation in stroke［J］. Circ Res， 2021， 128（1）： 62-75. doi:10.1161/circresaha.120.317596 |
| 2 | WANG Q， REPS J M， KOSTKA K F， et al. Development and validation of a prognostic model predicting symptomatic hemorrhagic transformation in acute ischemic stroke at scale in the OHDSI network［J］. PLoS One， 2020， 15（1）： e0226718. doi:10.1371/journal.pone.0226718 |
| 3 | ZHANG G， HE M， XU Y， et al. Hemoglobin A1c predicts hemorrhagic transformation and poor outcomes after acute anterior stroke［J］. Eur J Neurol， 2018， 25（12）： 1432-e122. doi:10.1111/ene.13747 |
| 4 | LV G， WANG G， XIA Z， et al. Influences of blood lipids on the occurrence and prognosis of hemorrhagic transformation after acute cerebral infarction： a case-control study of 732 patients［J］. Mil Med Res， 2019， 6（1）： 2. doi:10.1186/s40779-019-0191-z |
| 5 | 汪洋， 张辉， 伍冬冬， 等. 表没食子儿茶素没食子酸酯对低氧环境下肺心病大鼠呼吸衰竭的改善作用［J］. 实用医学杂志， 2022， 38（3）： 330-334. doi:10.3969/j.issn.1006-5725.2022.03.013 |
| 6 | 杨鹏， 郭倩， 许舒婷， 等. 靶向脑淀粉斑的载EGCG纳米递释系统的构建及其治疗阿尔茨海默病小鼠的研究［J］. 四川大学学报（医学版）， 2021， 52（4）： 605-611. |
| 7 | LUO Z L， SUN H Y， WU X B， et al. Epigallocatechin-3-gallate attenuates acute pancreatitis induced lung injury by targeting mitochondrial reactive oxygen species triggered NLRP3 inflammasome activation［J］. Food Funct， 2021， 12（12）： 5658-5667. doi:10.1039/d1fo01154e |
| 8 | HE H， WANG L， QIAO Y， et al. Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy［J］. Redox Biol， 2021， 48： 102185. doi:10.1016/j.redox.2021.102185 |
| 9 | DENG J， MEI H， SHI W， et al. Recombinant tissue plasminogen activator-conjugated nanoparticles effectively targets thrombolysis in a rat model of middle cerebral artery occlusion［J］. Curr Med Sci， 2018， 38（3）： 427-435. doi:10.1007/s11596-018-1896-z |
| 10 | ZHANG Y， HAN M， SUN X， et al. EGCG promotes neurite outgrowth through the integrin β1/FAK/p38 signaling pathway after subarachnoid hemorrhage［J］. Evid Based Complement Alternat Med， 2021， 2021： 8810414. doi:10.1155/2021/8810414 |
| 11 | CHEN C， CHU S， ZHANG Z， et al. CKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia［J］. Int Immunopharmacol， 2020， 85： 106577. doi:10.1016/j.intimp.2020.106577 |
| 12 | VAN KRANENDONK K R， TREURNIET K M， BOERS A M M， et al. Hemorrhagic transformation is associated with poor functional outcome in patients with acute ischemic stroke due to a large vessel occlusion［J］. J Neurointerv Surg， 2019， 11（5）： 464-468. doi:10.1136/neurintsurg-2018-014141 |
| 13 | YAN Y， AO L， ZHOU L， et al. Therapeutic effects of JLX001 on cerebral ischemia through inhibiting platelet activation and thrombus formation in rats［J］. Biomed Pharmacother， 2018， 106： 805-812. doi:10.1016/j.biopha.2018.07.023 |
| 14 | CHEN Y， KONG L， WANG H， et al. The role of pinocembrin in t-PA thrombolysis-induced hemorrhagic transformation［J］. Acta Pharm Sin， 2019： 448-453. |
| 15 | MACHIN A， SUSILO I， PURWANTO D A. Green tea and its active compound epigallocathechin-3-gallate （EGCG） inhibit neuronal apoptosis in a middle cerebral artery occlusion （MCAO） model［J］. J Basic Clin Physiol Pharmacol， 2021， 32（4）： 319-325. doi:10.1515/jbcpp-2020-0454 |
| 16 | QIN S， CHEN M， FANG W， et al. Cerebral protection of epigallocatechin gallate （EGCG） via preservation of mitochondrial function and ERK inhibition in a rat resuscitation model［J］. Drug Des Devel Ther， 2019， 13： 2759-2768. doi:10.2147/dddt.s215358 |
| 17 | CHEN L， CAO J， CAO D， et al. Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury： An in vivo and in vitro study［J］. Life Sci， 2019， 235： 116553. doi:10.1016/j.lfs.2019.116553 |
| 18 | CHEN H， GUAN B， CHEN S， et al. Peroxynitrite activates NLRP3 inflammasome and contributes to hemorrhagic transformation and poor outcome in ischemic stroke with hyperglycemia［J］. Free Radic Biol Med， 2021， 165： 171-183. doi:10.1016/j.freeradbiomed.2021.01.030 |
| 19 | ZHANG R， ZHU X， BAI H， et al. Network pharmacology databases for traditional Chinese medicine： review and assessment［J］. Front Pharmacol， 2019， 10： 123. doi:10.3389/fphar.2019.00123 |
| 20 | 王东娟， 李恒栋， 谢小玲， 等. 胰高血糖素样肽1通过Keap1-Nrf2信号通路减轻糖尿病大鼠心肌微血管损伤［J］. 中国病理生理杂志， 2019， 35（12）： 2143-2149. doi:10.3969/j.issn.1000-4718.2019.12.005 |
| 21 | IMAI T， TAKAGI T， KITASHOJI A， et al. Nrf2 activator ameliorates hemorrhagic transformation in focal cerebral ischemia under warfarin anticoagulation［J］. Neurobiol Dis， 2016， 89： 136-146. doi:10.1016/j.nbd.2016.02.001 |
| 22 | LEBDA M A， ELMASSRY I H， TAHA N M， et al. Nanocurcumin alleviates inflammation and oxidative stress in LPS-induced mastitis via activation of Nrf2 and suppressing TLR4-mediated NF-κB and HMGB1 signaling pathways in rats［J］. Environ Sci Pollut Res Int， 2022， 29（6）： 8294-8305. doi:10.1007/s11356-021-16309-9 |
| 23 | ZHANG R， LU M， ZHANG S， et al. Renoprotective effects of Tilianin in diabetic rats through modulation of oxidative stress via Nrf2-Keap1 pathway and inflammation via TLR4/MAPK/NF-κB pathways［J］. Int Immunopharmacol， 2020， 88： 106967. doi:10.1016/j.intimp.2020.106967 |
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