Diminazene Alleviates Neuroinflammation in Ischemic Stroke by Inhibiting Astrocytic Endoplasmic Reticulum Stress and Oxidative Stress | Neurochemical Research

Home Neurochemical Research Article
Diminazene Alleviates Neuroinflammation in Ischemic Stroke by Inhibiting Astrocytic Endoplasmic Reticulum Stress and Oxidative Stress
Research
Published: 21 August 2025
Volume 50, article number 272, (2025)
Cite this article
Neurochemical Research
Aims and scope
Submit manuscript
Caidong Liu, Qiang Peng, Shiyao Wang, Zhaohan Xu, Ye Hong, Lin Zhu, Mengmeng Gu, Jinfeng Lyu, Yingdong Zhang & Rui Duan
Abstract
Acute ischemic stroke (AIS) is a common medical emergency worldwide, and reducing cerebral ischemia/reperfusion injury (CI/RI) is a crucial strategy for AIS treatment. Diminazene aceturate (DIZE) has demonstrated therapeutic potential in alleviating neurodegenerative diseases, but its specific functions in AIS remain a puzzle. This research aims to investigate the role and mechanisms of DIZE in CI/RI. C57BL/6J mice were treated with DIZE via intracerebroventricular injection for a week and middle cerebral artery occlusion/reperfusion (MCAO/R) models were established. Neurobehavioral tests, TTC staining and HE staining were adapted to detect neuroprotective effect of DIZE on MCAO/R mice. Primary cultures of astrocytes were prepared and exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate in vitro ischemia/reperfusion. The IL-1β, IL-6 and TNF-α levels were detected by qRT-PCR and ELISA. Oxidative stress and lipid peroxidation indicators were measured using commercial assay kits. Western blot and immunofluorescence staining were used to measure the related protein levels. We found that DIZE alleviated neuronal injury and suppressed both neuroinflammation and astrocyte reactive changes in MCAO/R mice. In vitro, DIZE inhibited the release of inflammatory factors in primary cultures of astrocytes subjected to OGD/R. Furthermore, DIZE inhibited endoplasmic reticulum stress-mediated IRE1α-NF-κB pathway, increased NRF2 levels and suppressed oxidative stress, which was consistently observed in vivo and in vitro. Our study indicated that DIZE exerts a protective effect on CI/RI, and this effect may be achieved by DIZE inhibiting endoplasmic reticulum stress and oxidative stress in astrocytes, thereby suppressing astrocyte-mediated neuroinflammation.
This is a preview of subscription content, log in via an institution to check access.
Access this article
Log in via an institution
Subscribe and save
Springer+
from ¥17,985 /Month
Starting from 10 chapters or articles per month
Access and download chapters and articles from more than 300k books and 2,500 journals
Cancel anytime
View plans
Buy Now
Buy article PDF ￥ 4,980
Price includes VAT (Japan)
Instant access to the full article PDF.
Institutional subscriptions
Explore related subjects
Discover the latest articles, books and news in related subjects, suggested using machine learning.
Alzheimer's disease
Astrocyte
Brain Cancer
Cellular Stress
Neurology
Neurodegeneration
Data Availability
The data that support this study are available from the corresponding author upon reasonable request.
References
Lin W, Zhao XY, Cheng JW, Li LT, Jiang Q, Zhang YX, Han F (2023) Signaling pathways in brain ischemia: mechanisms and therapeutic implications. Pharmacol Ther 251:108541
CAS
PubMed
Google Scholar
Feigin VL, Brainin M, Norrving B, Martins S, Sacco RL, Hacke W, Fisher M, Pandian J, Lindsay P (2022) World stroke organization (WSO): global stroke fact sheet 2022. Int J Stroke: Official J Int Stroke Soc 17:18–29
Google Scholar
Katsanos AH, Tsivgoulis G (2019) Is intravenous thrombolysis still necessary in patients who undergo mechanical thrombectomy? Curr Opin Neurol 32:3–12
PubMed
Google Scholar
Gariel F, Lapergue B, Bourcier R, Berge J, Barreau X, Mazighi M, Kyheng M, Labreuche J, Fahed R, Blanc R, Gory B, Duhamel A, Saleme S, Costalat V, Bracard S, Desal H, Detraz L, Consoli A, Piotin M, Marnat G (2018) Mechanical thrombectomy outcomes with or without intravenous thrombolysis. Stroke 49:2383–2390
PubMed
Google Scholar
Wang X, Phillips MI, Mehta JL (2011) LOX-1 and angiotensin receptors, and their interplay. Cardiovasc Drugs Ther 25:401–417
CAS
PubMed
PubMed Central
Google Scholar
Bihl JC, Zhang C, Zhao Y, Xiao X, Ma X, Chen Y, Chen S, Zhao B, Chen Y (2015) Angiotensin-(1–7) counteracts the effects of Ang II on vascular smooth muscle cells, vascular remodeling and hemorrhagic stroke: role of the NFкB inflammatory pathway. Vascul Pharmacol 73:115–123
CAS
PubMed
PubMed Central
Google Scholar
Jiang T, Gao L, Lu J, Zhang YD (2013) ACE2-Ang-(1–7)-Mas axis in brain: a potential target for prevention and treatment of ischemic stroke. Curr Neuropharmacol 11:209–217
CAS
PubMed
PubMed Central
Google Scholar
Qaradakhi T, Gadanec LK, McSweeney KR, Tacey A, Apostolopoulos V, Levinger I, Rimarova K, Egom EE, Rodrigo L, Kruzliak P, Kubatka P, Zulli A (2020) The potential actions of angiotensin-converting enzyme II (ACE2) activator diminazene aceturate (DIZE) in various diseases. Clin Exp Pharmacol Physiol 47:751–758
CAS
PubMed
Google Scholar
Coutinho DCO, Santos-Miranda A, Joviano-Santos JV, Foureaux G, Santos A, Rodrigues-Ferreira C, Martins-Júnior PA, Resende RR, Medei E, Vieyra A, Santos RAS, Cruz JS, Ferreira AJ (2022) Diminazene aceturate, an angiotensin converting enzyme 2 (ACE2) activator, promotes cardioprotection in ischemia/reperfusion-induced cardiac injury. Peptides 151:170746
CAS
PubMed
Google Scholar
Li T, Huang HY, Wang HD, Gao CC, Liang H, Deng CL, Zhao X, Han YL, Zhou ML (2022) Restoration of brain angiotensin-converting enzyme 2 alleviates neurological deficits after severe traumatic brain injury via mitigation of pyroptosis and apoptosis. J Neurotrauma 39:423–434
PubMed
Google Scholar
Tiwari P, Elgazzaz M, Lazartigues E, Hanif K (2024) Effect of diminazene aceturate, an ACE2 activator, on platelet CD40L signaling induced glial activation in rat model of hypertension. Int Immunopharmacol 139:112654
CAS
PubMed
Google Scholar
Wang L, de Kloet AD, Pati D, Hiller H, Smith JA, Pioquinto DJ, Ludin JA, Oh SP, Katovich MJ, Frazier CJ, Raizada MK, Krause EG (2016) Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors. Neuropharmacology 105:114–123
PubMed
PubMed Central
Google Scholar
Evans CE, Miners JS, Piva G, Willis CL, Heard DM, Kidd EJ, Good MA, Kehoe PG (2020) ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of alzheimer’s disease. Acta Neuropathol 139:485–502
CAS
PubMed
PubMed Central
Google Scholar
Mecca AP, Regenhardt RW, O’Connor TE, Joseph JP, Raizada MK, Katovich MJ, Sumners C (2011) Cerebroprotection by angiotensin-(1–7) in endothelin-1-induced ischaemic stroke. Exp Physiol 96:1084–1096
CAS
PubMed
Google Scholar
Bennion DM, Haltigan EA, Irwin AJ, Donnangelo LL, Regenhardt RW, Pioquinto DJ, Purich DL, Sumners C (2015) Activation of the neuroprotective angiotensin-converting enzyme 2 in rat ischemic stroke. Hypertension 66:141–148
CAS
PubMed
Google Scholar
Ravichandran KA, Heneka MT (2024) Inflammasomes in neurological disorders - mechanisms and therapeutic potential. Nat Rev Neurol 20:67–83
PubMed
Google Scholar
Anrather J, Iadecola C (2016) Inflammation and stroke: an overview. Neurotherapeutics 13:661–670
CAS
PubMed
PubMed Central
Google Scholar
Ebadpour N, Mahmoudi M, Kamal Kheder R, Abavisani M, Baridjavadi Z, Abdollahi N, Esmaeili SA (2024) From mitochondrial dysfunction to neuroinflammation in Parkinson’s disease: pathogenesis and mitochondrial therapeutic approaches. Int Immunopharmacol 142:113015
CAS
PubMed
Google Scholar
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and alzheimer’s disease. Neurobiol Aging 21:383–421
CAS
PubMed
PubMed Central
Google Scholar
Gupta S, Tiwari V, Tiwari P, Parul, Mishra A, Hanif K, Shukla S (2022) Angiotensin-converting enzyme 2 activation mitigates behavioral deficits and neuroinflammatory burden in 6-OHDA induced experimental models of parkinson’s disease. ACS Chem Neurosci 13:1491–1504
CAS
PubMed
Google Scholar
Duan R, Xue X, Zhang QQ, Wang SY, Gong PY, Jiang EY, Zhang T YD (2020) ACE2 activator diminazene aceturate ameliorates alzheimer’s disease-like neuropathology and rescues cognitive impairment in SAMP8 mice. Aging 12:14819–14829
CAS
PubMed
PubMed Central
Google Scholar
Sun X, Deng Y, Ge P, Peng Q, Soufiany I, Zhu L, Duan R (2023) Diminazene ameliorates neuroinflammation by suppression of astrocytic miRNA-224-5p/NLRP3 axis in alzheimer’s disease model. J Inflamm Res 16:1639–1652
CAS
PubMed
PubMed Central
Google Scholar
Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453–462
CAS
PubMed
PubMed Central
Google Scholar
Shirley R, Ord EN, Work LM (2014) Oxidative stress and the use of antioxidants in stroke. Antioxid (Basel) 3:472–501
Google Scholar
Orellana-Urzúa S, Rojas I, Líbano L, Rodrigo R (2020) Pathophysiology of ischemic stroke: role of oxidative stress. Curr Pharm Des 26:4246–4260
PubMed
Google Scholar
Araki K, Nagata K (2011) Protein folding and quality control in the ER. Cold Spring Harb Perspect Biol 3:a007526
PubMed
PubMed Central
Google Scholar
Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13:89–102
CAS
PubMed
Google Scholar
Li Y, Li M, Feng S, Xu Q, Zhang X, Xiong X, Gu L (2024) Ferroptosis and endoplasmic reticulum stress in ischemic stroke. Neural Regen Res 19:611–618
CAS
PubMed
Google Scholar
Lin Y, Jiang M, Chen W, Zhao T, Wei Y (2019) Cancer and ER stress: mutual crosstalk between autophagy, oxidative stress and inflammatory response. Biomed Pharmacother 118:109249
CAS
PubMed
Google Scholar
Mosaoa RM, Al-Rabia MW, Asfour HZ, Alhakamy NA, Mansouri RA, El-Agamy DS, Abdulaal WH, Mohamed GA, Ibrahim SRM, Elshal M (2024) Targeting SIRT1/AMPK/Nrf2/NF-кB by sitagliptin protects against oxidative stress-mediated ER stress and inflammation during ANIT-induced cholestatic liver injury. Toxicology 507:153889
CAS
PubMed
Google Scholar
Jiang T, Xue LJ, Yang Y, Wang QG, Xue X, Ou Z, Gao Q, Shi JQ, Wu L, Zhang YD (2018) AVE0991, a nonpeptide analogue of Ang-(1–7), attenuates aging-related neuroinflammation. Aging 10:645–657
CAS
PubMed
PubMed Central
Google Scholar
Costa LA, Mourão FAG, Alenina N, Bader M, Campagnole-Santos MJ, Kangussu LM (2025) Diminazene aceturate (DIZE) ameliorates hypertension and induces anxiolytic- and antidepressant-like effects in TGR(mRen2)27. Protein Pept Lett 32:243-252
Kalange AS, Kokare DM, Singru PS, Upadhya MA, Chopde CT, Subhedar NK (2007) Central administration of selective melanocortin 4 receptor antagonist HS014 prevents morphine tolerance and withdrawal hyperalgesia. Brain Res 1181:10–20
CAS
PubMed
Google Scholar
Knight WD, Swoap SJ, Parsons AD, Overton JM (2006) Central thyrotropin-releasing hormone infusion opposes cardiovascular and metabolic suppression during caloric restriction. Neuroendocrinology 83:69–76
CAS
PubMed
Google Scholar
Yuan Y, Zhai Y, Chen J, Xu X, Wang H (2021) Kaempferol ameliorates oxygen-glucose deprivation/reoxygenation-induced neuronal ferroptosis by activating Nrf2/SLC7A11/GPX4 axis. Biomolecules 11:923
Schaar KL, Brenneman MM, Savitz SI (2010) Functional assessments in the rodent stroke model. Exp Transl Stroke Med 2:13
PubMed
PubMed Central
Google Scholar
Skauli N, Zohoorian N, Banitalebi S, Geiseler S, Salameh M, Rao SB, Morland C, Ottersen OP, Amiry-Moghaddam M (2024) Aquaporin-4 deletion leads to reduced infarct volume and increased peri-infarct astrocyte reactivity in a mouse model of cortical stroke. J Physiol 602:3151–3168
CAS
PubMed
Google Scholar
Liu X, Ye Q, Huang Z, Li X, Zhang L, Liu X, Wu YC, Brockmeier U, Hermann DM, Wang YC, Ren L (2023) BAG3 overexpression attenuates ischemic stroke injury by activating autophagy and inhibiting apoptosis. Stroke 54:2114–2125
CAS
PubMed
Google Scholar
Hu J, Duan H, Zou J, Ding W, Wei Z, Peng Q, Li Z, Duan R, Sun J, Zhu J (2024) METTL3-dependent N6-methyladenosine modification is involved in berberine-mediated neuroprotection in ischemic stroke by enhancing the stability of NEAT1 in astrocytes. Aging 16:299-321
Deng Y, Duan R, Ding W, Gu Q, Liu M, Zhou J, Sun J, Zhu J (2022) Astrocyte-derived exosomal nicotinamide phosphoribosyltransferase (Nampt) ameliorates ischemic stroke injury by targeting ampk/mtor signaling to induce autophagy. Cell Death Dis 13:1057
CAS
PubMed
PubMed Central
Google Scholar
Begum G, Kintner D, Liu Y, Cramer SW, Sun D (2012) DHA inhibits ER Ca2 + release and ER stress in astrocytes following in vitro ischemia. J Neurochem 120:622–630
CAS
PubMed
PubMed Central
Google Scholar
Qi J, Xian XH, Li L, Zhang M, Hu YY, Zhang JG, Li WB (2018) Sulbactam protects hippocampal neurons against oxygen-glucose deprivation by up-regulating astrocytic GLT-1 via p38 MAPK signal pathway. Front Mol Neurosci 11:281
PubMed
PubMed Central
Google Scholar
Babu M, Singh N, Datta A (2022) In vitro oxygen glucose deprivation model of ischemic stroke: a proteomics-driven systems biological perspective. Mol Neurobiol 59:2363–2377
CAS
PubMed
Google Scholar
Han Y, Yuan M, Guo YS, Shen XY, Gao ZK, Bi X (2021) Mechanism of endoplasmic reticulum stress in cerebral ischemia. Front Cell Neurosci 15:704334
CAS
PubMed
PubMed Central
Google Scholar
Li W, Cao T, Luo C, Cai J, Zhou X, Xiao X, Liu S (2020) Crosstalk between ER stress, NLRP3 inflammasome, and inflammation. Appl Microbiol Biotechnol 104:6129–6140
CAS
PubMed
Google Scholar
Zhou Y, Tong Z, Jiang S, Zheng W, Zhao J, Zhou X (2020) The roles of endoplasmic reticulum in NLRP3 inflammasome activation. Cells 9:1219
PubMed
PubMed Central
Google Scholar
Xu G, Dong F, Su L, Tan ZX, Lei M, Li L, Wen D, Zhang F (2024) The role and therapeutic potential of nuclear factor κB (NF-κB) in ischemic stroke. Biomed Pharmacother 171:116140
CAS
PubMed
Google Scholar
Christian F, Smith EL, Carmody RJ (2016) The regulation of NF-κB subunits by phosphorylation. Cells 5:12
Vomund S, Schäfer A, Parnham MJ, Brüne B, von Knethen A (2017) Nrf2, the master regulator of Anti-Oxidative responses. Int J Mol Sci 18:2772
Zhao Y, Zhang X, Chen X, Wei Y (2022) Neuronal injuries in cerebral infarction and ischemic stroke: from mechanisms to treatment (Review). Int J Mol Med 49:15
Wang H, Zhang S, Xie L, Zhong Z, Yan F (2023) Neuroinflammation and peripheral immunity: focus on ischemic stroke. Int Immunopharmacol 120:110332
CAS
PubMed
Google Scholar
Kuriakose S, Uzonna JE (2014) Diminazene aceturate (Berenil), a new use for an old compound? Int Immunopharmacol 21:342–345
CAS
PubMed
Google Scholar
Qiu Y, Shil PK, Zhu P, Yang H, Verma A, Lei B, Li Q (2014) Angiotensin-converting enzyme 2 (ACE2) activator diminazene aceturate ameliorates endotoxin-induced uveitis in mice. Invest Ophthalmol Vis Sci 55:3809–3818
CAS
PubMed
PubMed Central
Google Scholar
Shenoy V, Gjymishka A, Jarajapu YP, Qi Y, Afzal A, Rigatto K, Ferreira AJ, Fraga-Silva RA, Kearns P, Douglas JY, Agarwal D, Mubarak KK, Bradford C, Kennedy WR, Jun JY, Rathinasabapathy A, Bruce E, Gupta D, Cardounel AJ, Mocco J, Patel JM, Francis J, Grant MB, Katovich MJ, Raizada MK (2013) Diminazene attenuates pulmonary hypertension and improves angiogenic progenitor cell functions in experimental models. Am J Respir Crit Care Med 187:648–657
CAS
PubMed
PubMed Central
Google Scholar
Giovannoni F, Quintana FJ (2020) The role of astrocytes in CNS inflammation. Trends Immunol 41:805–819
CAS
PubMed
PubMed Central
Google Scholar
Cekanaviciute E, Buckwalter MS (2016) Astrocytes: integrative regulators of neuroinflammation in stroke and other neurological diseases. Neurotherapeutics 13:685–701
CAS
PubMed
PubMed Central
Google Scholar
Jiang N, Wang C, Xie B, Xie H, Wu A, Kong X, Gu L, Jiang Y, Peng J (2024) Identification of endoplasmic reticulum stress genes in human stroke based on bioinformatics and machine learning. Neurobiol Dis 199:106583
CAS
PubMed
Google Scholar
Sovolyova N, Healy S, Samali A, Logue SE (2014) Stressed to death - mechanisms of ER stress-induced cell death. Biol Chem 395:1–13
CAS
PubMed
Google Scholar
Peng Q, Wang S, Huang S, Deng Y, Li Z, Liu C, Hong Y, Duan R, Xue X, Ge P (2025) FTO/miR-503-5p/USP10 axis regulates neuronal endoplasmic reticulum stress-mediated apoptosis in ischemic stroke. Int Immunopharmacol 149:114150
CAS
PubMed
Google Scholar
Sims SG, Cisney RN, Lipscomb MM, Meares GP (2022) The role of endoplasmic reticulum stress in astrocytes. Glia 70:5–19
CAS
PubMed
Google Scholar
Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–1086
CAS
PubMed
Google Scholar
Kou JJ, Shi JZ, He YY, Hao JJ, Zhang HY, Luo DM, Song JK, Yan Y, Xie XM, Du GH, Pang XB (2022) Luteolin alleviates cognitive impairment in Alzheimer’s disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation. Acta Pharmacol Sin 43:840–849
CAS
PubMed
Google Scholar
Meng F, Song J, Huang X, Zhang M, Sun X, Jing Q, Cao S, Xie Z, Liu Q, Zhang H, Li C (2024) Inhibiting endoplasmic reticulum stress alleviates perioperative neurocognitive disorders by reducing neuroinflammation mediated by NLRP3 inflammasome activation. CNS Neurosci Ther 30:e70049
CAS
PubMed
PubMed Central
Google Scholar
Rajapaksha IG, Mak KY, Huang P, Burrell LM, Angus PW, Herath CB (2018) The small molecule drug diminazene aceturate inhibits liver injury and biliary fibrosis in mice. Sci Rep 8:10175
PubMed
PubMed Central
Google Scholar
Wang LF, Sun YY, Pan Q, Yin YQ, Tian XM, Liu Y, Bu T, Zhang Q, Wang YA, Zhao J, Luo Y (2021) Diminazen aceturate protects pulmonary ischemia-reperfusion injury via inhibition of ADAM17-mediated angiotensin-converting enzyme 2 shedding. Front Pharmacol 12:713632
CAS
PubMed
PubMed Central
Google Scholar
Ramos-González EJ, Bitzer-Quintero OK, Ortiz G, Hernández-Cruz JJ, Ramírez-Jirano LJ (2024) Relationship between inflammation and oxidative stress and its effect on multiple sclerosis. Neurologia (Engl Ed) 39:292–301
PubMed
Google Scholar
Yoon SH, Kang HB, Kim J, Yoo K, Han SJ (2022) Diminazene aceturate attenuates hepatic ischemia/reperfusion injury in mice. Sci Rep 12:18158
CAS
PubMed
PubMed Central
Google Scholar
Fang Y, Gao F, Liu Z (2019) Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways. QJM 112:914–924
CAS
PubMed
Google Scholar
Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K (2014) Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int 2014:761264
PubMed
PubMed Central
Google Scholar
Tu W, Wang H, Li S, Liu Q, Sha H (2019) The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging Dis 10:637–651
PubMed
PubMed Central
Google Scholar
Takagi T, Kitashoji A, Iwawaki T, Tsuruma K, Shimazawa M, Yoshimura S, Iwama T, Hara H (2014) Temporal activation of Nrf2 in the penumbra and Nrf2 activator-mediated neuroprotection in ischemia-reperfusion injury. Free Radic Biol Med 72:124–133
CAS
PubMed
Google Scholar
Shokri F, Zarei M, Komaki A, Raoufi S, Ramezani-Aliakbari F (2024) Effect of diminazene on cardiac hypertrophy through mitophagy in rat models with hyperthyroidism induced by levothyroxine. Naunyn Schmiedebergs Arch Pharmacol 397:1151–1162
CAS
PubMed
Google Scholar
Chen L, Zhao X, Sheng R, Lazarovici P, Zheng W (2025) Artemisinin alleviates astrocyte overactivation and neuroinflammation by modulating the IRE1/NF-κB signaling pathway in in vitro and in vivo Alzheimer’s disease models. Free Radic Biol Med 229:96–110
CAS
PubMed
Google Scholar
Cao SS, Luo KL, Shi L (2016) Endoplasmic reticulum stress interacts with inflammation in human diseases. J Cell Physiol 231:288–294
CAS
PubMed
Google Scholar
Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Et Biophys Acta Mol Basis Dis 1863:585–597
CAS
Google Scholar
Nakka VP, Prakash-Babu P, Vemuganti R (2016) Crosstalk between endoplasmic reticulum stress, oxidative stress, and autophagy: potential therapeutic targets for acute CNS injuries. Mol Neurobiol 53:532–544
CAS
PubMed
Google Scholar
Mozzini C, Cominacini L, Garbin U, Fratta Pasini AM (2017) Endoplasmic reticulum stress, NRF2 signalling and cardiovascular diseases in a nutshell. Curr Atheroscler Rep 19:33
PubMed
Google Scholar
Yuvaraj S, Ajeeth AK, Puhari SSM, Abhishek A, Ramprasath T, Vasudevan V, Vignesh N, Selvam GS (2023) Chrysin protects cardiac H9c2 cells against H2O2-induced endoplasmic reticulum stress by up-regulating the Nrf2/PERK pathway. Mol Cell Biochem 478:539–553
CAS
PubMed
Google Scholar
Download references
Funding
This study was funded by the National Natural Science Foundation of China (82301609), Natural Science Foundation of Jiangsu Province (BK20220196), China Postdoctoral Science Foundation (2022M711666), Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202239) and Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health (YKK22107).
Author information
Author notes
Caidong Liu, Qiang Peng and Shiyao Wang contributed equally to this work.
Authors and Affiliations
Department of Blood Transfusion, Nanjing First Hospital, Pharmaceutical University, Nanjing, 210006, Jiangsu, People’s Republic of China
Caidong Liu
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210006, Jiangsu, People’s Republic of China
Caidong Liu, Yingdong Zhang & Rui Duan
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, People’s Republic of China
Qiang Peng, Shiyao Wang, Zhaohan Xu, Ye Hong, Lin Zhu, Mengmeng Gu, Jinfeng Lyu, Yingdong Zhang & Rui Duan
Contributions
YZ and RD designed and conducted this study. CL, QP and SW performed the experiments and wrote the manuscript. ZX, YH and LZ analyzed the data. MG and JL visualized the data. All authors read and approved the final manuscript.
Corresponding authors
Correspondence to Yingdong Zhang or Rui Duan.
Ethics declarations
Competing Interests
The authors declare no competing interests.
Ethical Approval
The study was approved by the Ethics Committee of Nanjing First Hospital, Nanjing Medical University (approval number: DWSY-23146450). The experimental protocol was conducted as per the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Reprints and permissions
About this article
Cite this article
Liu, C., Peng, Q., Wang, S. et al. Diminazene Alleviates Neuroinflammation in Ischemic Stroke by Inhibiting Astrocytic Endoplasmic Reticulum Stress and Oxidative Stress. Neurochem Res 50, 272 (2025). https://doi.org/10.1007/s11064-025-04530-8
Download citation
Received
22 April 2025
Revised
02 August 2025
Accepted
04 August 2025
Published
21 August 2025
DOI
https://doi.org/10.1007/s11064-025-04530-8
Keywords
Ischemic stroke
DIZE
Endoplasmic reticulum stress
Oxidative stress
Inflammation