{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:38:30Z","timestamp":1791293910732,"version":"4.1.0"},"reference-count":161,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Brain ischemia-reperfusion (I\/R) injury, commonly occurring in ischemic stroke and post-cardiac arrest scenarios, results in complex secondary damage involving oxidative stress, inflammation, apoptosis, and blood-brain barrier (BBB) breakdown. Despite decades of research, no pharmacological agent has yet been clinically approved for post-I\/R neuroprotection. Natural compounds have recently gained attention for their multimodal therapeutic potential, including antioxidant, anti-inflammatory, anti-apoptotic, and neuroregenerative effects. This review highlights nine promising candidates\u2014resveratrol, curcumin, quercetin, berberine, ginkgolide B, baicalin, naringin, fucoidan, and astaxanthin\u2014that exhibit efficacy in experimental models of I\/R injury when administered after the insult. Their chemical structures, pharmacokinetics, and mechanisms of action are described in detail, focusing on key signaling pathways such as nuclear factor erythroid 2-related (Nrf2), nuclear factor kappa B (NF-\u03baB), phosphatidylinositol 3-kinase\/protein kinase B (PI3K\/Akt), and brain-derived neurotrophic factor (BDNF). Importantly, we outline the selection criteria for these compounds, including demonstrated neuroprotective efficacy, mechanistic clarity, and translational feasibility. While several challenges remain\u2014such as limited bioavailability, BBB penetration, and species-specific metabolism\u2014emerging strategies like nanoparticle delivery, synthetic analogs, and drug combinations offer potential solutions. By emphasizing the therapeutic versatility and mechanistic diversity of these natural agents, this review supports their clinical potential and encourages further preclinical optimization and biomarker-guided human trials.<\/jats:p>","DOI":"10.3390\/biology14091153","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:28:15Z","timestamp":1756715295000},"page":"1153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic Potential of Natural Compounds for Brain Ischemia-Reperfusion Injury"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-275X","authenticated-orcid":false,"given":"Ki-Yeon","family":"Yoo","sequence":"first","affiliation":[{"name":"Department of Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea"},{"name":"Research Institute for Dental Engineering, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-6501","authenticated-orcid":false,"given":"Moo-Ho","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyeon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan 50510, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Ha","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.2174\/1570159X22666240131121032","article-title":"Metabolic reprogramming in Gliocyte post-cerebral ischemia\/reperfusion: From pathophysiology to therapeutic potential","volume":"22","author":"Gong","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neuroscience.2022.10.020","article-title":"Emerging Treatment Strategies for Cerebral Ischemia\u2013Reperfusion Injury","volume":"507","author":"Li","year":"2022","journal-title":"Neuroscience"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1001\/jama.2020.26867","article-title":"Diagnosis and management of transient ischemic attack and acute ischemic stroke: A review","volume":"325","author":"Mendelson","year":"2021","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lochhead, J.J., Ronaldson, P.T., and Davis, T.P. (2024). The role of oxidative stress in blood\u2013brain barrier disruption during ischemic stroke: Antioxidants in clinical trials. Biochem. Pharmacol., 228.","DOI":"10.1016\/j.bcp.2024.116186"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1552127","DOI":"10.1155\/2021\/1552127","article-title":"Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia\/macrophage pyroptosis through NF-\u03baB suppression and NLRP3 inflammasome inhibition","volume":"2021","author":"Ran","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhang, X., Xiong, X., Zhu, H., Chen, R., Zhang, S., Chen, G., and Jian, Z. (2022). Nrf2 regulates oxidative stress and its role in cerebral ischemic stroke. Antioxidants, 11.","DOI":"10.3390\/antiox11122377"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104877","DOI":"10.1016\/j.phrs.2020.104877","article-title":"Therapeutic targets of oxidative\/nitrosative stress and neuroinflammation in ischemic stroke: Applications for natural product efficacy with omics and systemic biology","volume":"158","author":"Chen","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhu, T., Wang, L., Wang, L.-p., and Wan, Q. (2022). Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke: Applications for natural compounds from medicinal herbs. Biomed. Pharmacother., 148.","DOI":"10.1016\/j.biopha.2022.112719"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s13244-018-0624-3","article-title":"Clinical applications of diffusion weighted imaging in neuroradiology","volume":"9","author":"Boto","year":"2018","journal-title":"Insights Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/toxsci\/kfw167","article-title":"Hydroquinone strongly alleviates focal ischemic brain injury via blockage of blood\u2013brain barrier disruption in rats","volume":"154","author":"Yoo","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_11","first-page":"107","article-title":"Altered Nurr1 protein expression in the hippocampal CA1 region following transient global cerebral ischemia","volume":"21","author":"Park","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, L., Jiang, W., Yu, B., Liang, H., Mao, S., Hu, X., Feng, Y., Xu, J., and Chu, L. (2023). Quercetin improves cerebral ischemia\/reperfusion injury by promoting microglia\/macrophages M2 polarization via regulating PI3K\/Akt\/NF-\u03baB signaling pathway. Biomed. Pharmacother., 168.","DOI":"10.1016\/j.biopha.2023.115653"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1016\/j.bmcl.2015.07.014","article-title":"Cheminformatic comparison of approved drugs from natural product versus synthetic origins","volume":"25","author":"Stratton","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s10753-020-01212-1","article-title":"lncRNA ZFAS1 improves neuronal injury and inhibits inflammation, oxidative stress, and apoptosis by sponging miR-582 and upregulating NOS3 expression in cerebral ischemia\/reperfusion injury","volume":"43","author":"Zhang","year":"2020","journal-title":"Inflammation"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Z., and Xing, J. (2024). Nuclear factor erythroid 2-related factor-mediated signaling alleviates ferroptosis during cerebral ischemia-reperfusion injury. Biomed. Pharmacother., 180.","DOI":"10.1016\/j.biopha.2024.117513"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1007\/s11064-022-03565-5","article-title":"Dose-dependent effects of astaxanthin on ischemia\/reperfusion induced brain injury in mcao model rat","volume":"47","author":"Taheri","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1590\/S0102-86502013000800003","article-title":"Oxidative stress evaluation of ischemia and reperfusion in kidneys under various degrees of hypothermia in rats","volume":"28","author":"Santos","year":"2013","journal-title":"Acta Cir. Bras."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1134\/S1607672924600313","article-title":"Neuroprotective Effect of Ganoderic Acid against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion in the Rats via Suppression of Oxidative Stress and Inflammation","volume":"518","author":"Liu","year":"2024","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-0102(01)00282-6","article-title":"Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils","volume":"41","author":"Mhadu","year":"2001","journal-title":"Neurosci. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0168-0102(03)00184-6","article-title":"Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils","volume":"47","author":"Alvarez","year":"2003","journal-title":"Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, G.E., Tae, H.J., Lee, T.K., Park, Y.E., Cho, J.H., Kim, D.W., Park, J.H., Ahn, J.H., Ryoo, S., and Kim, Y.M. (2019). Risperidone Treatment after Transient Ischemia Induces Hypothermia and Provides Neuroprotection in the Gerbil Hippocampus by Decreasing Oxidative Stress. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184621"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Park, J.H., Lee, T.K., Kim, D.W., Sim, H., Lee, J.C., Kim, J.D., Ahn, J.H., Lee, C.H., Kim, Y.M., and Won, M.H. (2021). Neuroprotective Effects of Salicin in a Gerbil Model of Transient Forebrain Ischemia by Attenuating Oxidative Stress and Activating PI3K\/Akt\/GSK3beta Pathway. Antioxidants, 10.","DOI":"10.3390\/antiox10040629"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.neulet.2008.04.058","article-title":"Genistein attenuates oxidative stress and neuronal damage following transient global cerebral ischemia in rat hippocampus","volume":"438","author":"Liang","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s10571-009-9365-7","article-title":"Effect of antioxidant treatment in global ischemia and ischemic postconditioning in the rat hippocampus","volume":"29","author":"Domorakova","year":"2009","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s11011-024-01410-y","article-title":"Morin attenuated the global cerebral ischemia via antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats","volume":"39","author":"Alla","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"112915","DOI":"10.1016\/j.intimp.2024.112915","article-title":"Erianin alleviates cerebral ischemia-reperfusion injury by inhibiting microglial cell polarization and inflammation via the PI3K\/AKT and NF-kappaB pathways","volume":"141","author":"Jia","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.nbd.2015.03.028","article-title":"Astrocytic response to cerebral ischemia is influenced by sex differences and impaired by aging","volume":"85","author":"Chisholm","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7355","DOI":"10.1523\/JNEUROSCI.0115-20.2020","article-title":"Neuron-Derived Estrogen Is Critical for Astrocyte Activation and Neuroprotection of the Ischemic Brain","volume":"40","author":"Lu","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s11626-023-00846-3","article-title":"Administration with curcumin alleviates spinal cord ischemia-reperfusion injury by regulating anti-oxidative stress and microglia activation-mediated neuroinflammation via Nrf2\/NF-kappaB axis","volume":"60","author":"Wu","year":"2024","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jns.2010.06.004","article-title":"Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide","volume":"296","author":"Yu","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kim, D.W., Lee, T.K., Ahn, J.H., Yang, S.R., Shin, M.C., Cho, J.H., Won, M.H., Kang, I.J., and Park, J.H. (2024). Porphyran Attenuates Neuronal Loss in the Hippocampal CA1 Subregion Induced by Ischemia and Reperfusion in Gerbils by Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation. Mar. Drugs, 22.","DOI":"10.3390\/md22040170"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.5213\/inj.2014.18.3.115","article-title":"Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase\/Protein Kinase B Signaling Pathway","volume":"18","author":"Kim","year":"2014","journal-title":"Int. Neurourol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s12264-022-00859-0","article-title":"Neuronal death mechanisms and therapeutic strategy in ischemic stroke","volume":"38","author":"Mao","year":"2022","journal-title":"Neurosci. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"468","DOI":"10.17113\/ftb.52.04.14.3622","article-title":"Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity","volume":"52","author":"Chang","year":"2014","journal-title":"Food Technol. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0304-3940(92)90108-J","article-title":"Neuroprotective actions of riluzole in rodent models of global and focal cerebral ischaemia","volume":"140","author":"Pratt","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0014-2999(93)90804-Q","article-title":"Effect of riluzole on focal cerebral ischemia in rats","volume":"230","author":"Wahl","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1161\/STROKEAHA.107.506048","article-title":"Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat","volume":"39","author":"Sun","year":"2008","journal-title":"Stroke"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00701-003-0013-6","article-title":"Neuroprotective efficacy of intra-arterial and intravenous magnesium sulfate in a rat model of transient focal cerebral ischemia","volume":"145","author":"Westermaier","year":"2003","journal-title":"Acta Neurochir."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2174\/1568007053544183","article-title":"NMDA\/NR2B selective antagonists in the treatment of ischemic brain injury","volume":"4","author":"Wang","year":"2005","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12974-024-03033-7","article-title":"Mitochondrial stress: A key role of neuroinflammation in stroke","volume":"21","author":"Gao","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","article-title":"Reperfusion injury and reactive oxygen species: The evolution of a concept","volume":"6","author":"Granger","year":"2015","journal-title":"Redox Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0024-3205(02)02267-1","article-title":"Restricted clinical efficacy of cyclosporin A on rat transient middle cerebral artery occlusion","volume":"72","author":"Matsumoto","year":"2002","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.expneurol.2010.06.009","article-title":"Evaluation of cyclosporine A in a stroke model in the immature rat brain","volume":"230","author":"Leger","year":"2011","journal-title":"Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"121895","DOI":"10.1016\/j.lfs.2023.121895","article-title":"MitoQ alleviates hippocampal damage after cerebral ischemia: The potential role of SIRT6 in regulating mitochondrial dysfunction and neuroinflammation","volume":"328","author":"Ibrahim","year":"2023","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s12031-016-0843-3","article-title":"Prevention of Cyclophilin D-Mediated mPTP Opening Using Cyclosporine-A Alleviates the Elevation of Necroptosis, Autophagy and Apoptosis-Related Markers Following Global Cerebral Ischemia-Reperfusion","volume":"61","author":"Fakharnia","year":"2017","journal-title":"J. Mol. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.molbrainres.2003.11.006","article-title":"Neuroprotection by cyclosporin A following transient brain ischemia correlates with the inhibition of the early efflux of cytochrome C to cytoplasm","volume":"121","author":"Buzanska","year":"2004","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101883","DOI":"10.1016\/j.mito.2024.101883","article-title":"Mitochondrial mechanisms in Cerebral Ischemia-Reperfusion Injury: Unravelling the intricacies","volume":"77","author":"Singh","year":"2024","journal-title":"Mitochondrion"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lan, X., Wang, Q., Liu, Y., You, Q., Wei, W., Zhu, C., Hai, D., Cai, Z., Yu, J., and Zhang, J. (2024). Isoliquiritigenin alleviates cerebral ischemia-reperfusion injury by reducing oxidative stress and ameliorating mitochondrial dysfunction via activating the Nrf2 pathway. Redox Biol., 77.","DOI":"10.1016\/j.redox.2024.103406"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"tkad016","DOI":"10.1093\/burnst\/tkad016","article-title":"Regulated necrosis pathways: A potential target for ischemic stroke","volume":"11","author":"Ren","year":"2023","journal-title":"Burn. Trauma."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41392-023-01688-x","article-title":"Ischemia-reperfusion injury: Molecular mechanisms and therapeutic targets","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shen, M., Wu, R.X., Zhao, L., Li, J., Guo, H.T., Fan, R., Cui, Y., Wang, Y.M., Yue, S.Q., and Pei, J.M. (2012). Resveratrol attenuates ischemia\/reperfusion injury in neonatal cardiomyocytes and its underlying mechanism. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051223"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphotobiol.2018.05.010","article-title":"Curcumin attenuates cerebral ischemia injury in Sprague-Dawley rats and PC12 cells by suppressing overactivated autophagy","volume":"184","author":"Zhang","year":"2018","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"He, R., Jiang, Y., Shi, Y., Liang, J., and Zhao, L. (2020). Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis. Mater. Sci. Eng. C Mater. Biol. Appl., 117.","DOI":"10.1016\/j.msec.2020.111314"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1111\/j.1460-9568.2012.08229.x","article-title":"Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3beta and CREB through PI3-K\/Akt pathways","volume":"36","author":"Simao","year":"2012","journal-title":"Eur. J. Neurosci."},{"key":"ref_55","first-page":"358","article-title":"Assessment of global ischemic\/reperfusion and Tacrolimus administration on CA1 region of hippocampus: Gene expression profiles of BAX and BCL2 genes","volume":"117","author":"Badr","year":"2016","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_56","first-page":"1532","article-title":"Effects of magnesium sulfate on neuron apoptosis and expression of caspase-3, bax and bcl-2 after cerebral ischemia-reperfusion injury","volume":"116","author":"Zhou","year":"2003","journal-title":"Chin. Med. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"C135","DOI":"10.1152\/ajpcell.00136.2018","article-title":"Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke","volume":"316","author":"Yang","year":"2019","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"C343","DOI":"10.1152\/ajpcell.00095.2018","article-title":"Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection","volume":"315","author":"Abdullahi","year":"2018","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zheng, X., Ren, B., and Gao, Y. (2023). Tight junction proteins related to blood-brain barrier and their regulatory signaling pathways in ischemic stroke. Biomed. Pharmacother., 165.","DOI":"10.1016\/j.biopha.2023.115272"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Filchenko, I., Blochet, C., Buscemi, L., Price, M., Badaut, J., and Hirt, L. (2020). Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00371"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00109-020-01920-z","article-title":"CU06-1004 (endothelial dysfunction blocker) ameliorates astrocyte end-feet swelling by stabilizing endothelial cell junctions in cerebral ischemia\/reperfusion injury","volume":"98","author":"Kim","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/sj.jcbfm.9600375","article-title":"Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat","volume":"27","author":"Yang","year":"2007","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_65","first-page":"8509","article-title":"Retigabine protects the blood-brain barrier by regulating tight junctions between cerebral vascular endothelial cells in cerebral ischemia-reperfusion rats","volume":"22","author":"Zhao","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s11011-025-01570-5","article-title":"Effects of a mitochondrial calcium uniporter and P-selectin inhibitors on neural injury induced by global cerebral ischemia-reperfusion in male rats","volume":"40","author":"Javanmardi","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1007\/s11064-011-0526-y","article-title":"Effect of baicalin on matrix metalloproteinase-9 expression and blood-brain barrier permeability following focal cerebral ischemia in rats","volume":"36","author":"Tu","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/mmr.2017.6671","article-title":"Transient cerebral ischemia induces albumin expression in microglia only in the CA1 region of the gerbil hippocampus","volume":"16","author":"Park","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1007\/s11064-021-03362-6","article-title":"Comparison of Neuronal Death, Blood-Brain Barrier Leakage and Inflammatory Cytokine Expression in the Hippocampal CA1 Region Following Mild and Severe Transient Forebrain Ischemia in Gerbils","volume":"46","author":"Lee","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lee, T.K., Kang, I.J., Sim, H., Lee, J.C., Ahn, J.H., Kim, D.W., Park, J.H., Lee, C.H., Kim, J.D., and Won, M.H. (2021). Therapeutic Effects of Decursin and Angelica gigas Nakai Root Extract in Gerbil Brain after Transient Ischemia via Protecting BBB Leakage and Astrocyte Endfeet Damage. Molecules, 26.","DOI":"10.3390\/molecules26082161"},{"key":"ref_71","first-page":"3445","article-title":"Animal models of ischemic stroke and their application in clinical research","volume":"9","author":"Fluri","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chen, Q., Wan, J., Zhang, Y., He, Y., Bao, Y., Yu, L., and Yang, J. (2022). Pharmacokinetic-pharmacodynamic modeling analysis for hydroxysafflor yellow A-calycosin in compatibility in normal and cerebral ischemic rats: A comparative study. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.112950"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1161\/STROKEAHA.122.041354","article-title":"Improving Large Animal Ischemic Stroke Models for Translational Studies in the Era of Recanalization","volume":"54","author":"Li","year":"2023","journal-title":"Stroke"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s12975-023-01164-2","article-title":"Neutralizing RGMa with Elezanumab Promotes Cerebroprotection and Recovery in Rabbit Middle Cerebral Artery Occlusion","volume":"15","author":"Jacobson","year":"2024","journal-title":"Transl. Stroke Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/0091270006299090","article-title":"Pharmacokinetics of arundic acid, an astrocyte modulating agent, in acute ischemic stroke","volume":"47","author":"Ishibashi","year":"2007","journal-title":"J. Clin. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"106832","DOI":"10.1016\/j.ejps.2024.106832","article-title":"Safety, tolerability, and pharmacokinetic of HY0721 in Chinese healthy subjects: A first-in-human randomized, double-blind, placebo-controlled dose escalation phase I study","volume":"200","author":"Zhang","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100013","DOI":"10.1124\/jpet.124.002152","article-title":"Evaluation of systemic and brain pharmacokinetic parameters for repurposing metformin using intravenous bolus administration","volume":"392","author":"Sharma","year":"2025","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, Y., Han, Y., Tian, Y., Wu, P., Xin, A., Wei, X., Shi, Y., Zhang, Z., and Su, G. (2020). Pharmacokinetics, tissue distribution, and safety evaluation of a ligustilide derivative (LIGc). J. Pharm. Biomed. Anal., 182.","DOI":"10.1016\/j.jpba.2020.113140"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e34121","DOI":"10.1016\/j.heliyon.2024.e34121","article-title":"A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke","volume":"10","author":"Owjfard","year":"2024","journal-title":"Heliyon"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"105725","DOI":"10.1016\/j.phrs.2021.105725","article-title":"Resveratrol and endothelial function: A literature review","volume":"170","author":"Parsamanesh","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.nbd.2015.08.018","article-title":"Sustained neurological recovery induced by resveratrol is associated with angioneurogenesis rather than neuroprotection after focal cerebral ischemia","volume":"83","author":"Hermann","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1139\/cjpp-2019-0188","article-title":"Effects of resveratrol postconditioning on cerebral ischemia in mice: Role of the sirtuin-1 pathway","volume":"97","author":"Grewal","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.pneurobio.2016.06.006","article-title":"Mitochondrial function in hypoxic ischemic injury and influence of aging","volume":"157","author":"Ham","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"79247","DOI":"10.18632\/oncotarget.13018","article-title":"Resveratrol post-treatment protects against neonatal brain injury after hypoxia-ischemia","volume":"7","author":"Pan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Shi, N., Zhu, C., and Li, L. (2016). Rehabilitation Training and Resveratrol Improve the Recovery of Neurological and Motor Function in Rats after Cerebral Ischemic Injury through the Sirt1 Signaling Pathway. Biomed. Res. Int., 2016.","DOI":"10.1155\/2016\/1732163"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00280-010-1525-4","article-title":"Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats","volume":"68","author":"Kapetanovic","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Marton, L.T., Pescinini-e-Salzedas, L.M., Camargo, M.E.C., Barbalho, S.M., Haber, J.F.d.S., Sinatora, R.V., Detregiachi, C.R.P., Girio, R.J., Buchaim, D.V., and Cincotto dos Santos Bueno, P. (2021). The effects of curcumin on diabetes mellitus: A systematic review. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.669448"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Yang, K., Zeng, L., He, Q., Wang, S., Xu, H., and Ge, J. (2024). Advancements in research on the immune-inflammatory mechanisms mediated by NLRP3 inflammasome in ischemic stroke and the regulatory role of natural plant products. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1250918"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Liu, Z., Ran, Y., Huang, S., Wen, S., Zhang, W., Liu, X., Ji, Z., Geng, X., Ji, X., and Du, H. (2017). Curcumin Protects against Ischemic Stroke by Titrating Microglia\/Macrophage Polarization. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00233"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1002\/ptr.6334","article-title":"Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials","volume":"33","author":"Ostadmohammadi","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1002\/ptr.7144","article-title":"Quercetin and metabolic syndrome: A review","volume":"35","author":"Hosseini","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1080\/10286020.2021.1949302","article-title":"Quercetin attenuates ischemia reperfusion injury by protecting the blood-brain barrier through Sirt1 in MCAO rats","volume":"24","author":"Yang","year":"2022","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Mahyar, M., Ghadirzadeh, E., Nezhadnaderi, P., Moayedi, Z., Maboud, P., Ebrahimi, A., Siahposht-Khachaki, A., and Karimi, N. (2025). Neuroprotective effects of quercetin on hippocampal CA1 neurons following middle cerebral artery ischemia-reperfusion in male rats: A behavioral, biochemical, and histological study. BMC Neurol., 25.","DOI":"10.1186\/s12883-024-04017-z"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/S0891-5849(00)00195-7","article-title":"Bioavailability and metabolism of the flavonol quercetin in the pig","volume":"28","author":"Ader","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"104385","DOI":"10.1016\/j.phrs.2019.104385","article-title":"Berberine protects against ischemia-reperfusion injury: A review of evidence from animal models and clinical studies","volume":"148","author":"Liu","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/03602532.2017.1306544","article-title":"The metabolism of berberine and its contribution to the pharmacological effects","volume":"49","author":"Wang","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhao, L., Li, H., Gao, Q., Xu, J., Zhu, Y., Zhai, M., Zhang, P., Shen, N., Di, Y., and Wang, J. (2021). Berberine attenuates cerebral ischemia-reperfusion injury induced neuronal apoptosis by down-regulating the CNPY2 signaling pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.609693"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jchemneu.2017.04.008","article-title":"Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines","volume":"87","author":"Maleki","year":"2018","journal-title":"J. Chem. Neuroanat."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1124\/dmd.110.033936","article-title":"Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats","volume":"38","author":"Liu","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.2174\/1568026615666150610142647","article-title":"Neuroprotective Effects of Ginkgolide B Against Ischemic Stroke: A Review of Current Literature","volume":"15","author":"Nabavi","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.apsb.2023.09.014","article-title":"Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba","volume":"14","author":"Ye","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.4103\/1673-5374.232476","article-title":"Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia\/reperfusion injury, both in vivo and in vitro","volume":"13","author":"Zheng","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ejps.2011.07.014","article-title":"Therapeutic neuroprotective effects of ginkgolide B on cortex and basal ganglia in a rat model of transient focal ischemia","volume":"44","author":"Lv","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_106","first-page":"137","article-title":"[Pharmacokinetic properties of Bilobalide and Ginkgolides A and B in healthy subjects after intravenous and oral administration of Ginkgo biloba extract (EGb 761)]","volume":"50","author":"Fourtillan","year":"1995","journal-title":"Therapie"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Wen, Y., Wang, Y., Zhao, C., Zhao, B., and Wang, J. (2023). The pharmacological efficacy of baicalin in inflammatory diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119317"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bbrc.2010.11.042","article-title":"Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor kappaB p65 activation","volume":"403","author":"Xue","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.lfs.2005.04.072","article-title":"Absorption and enterohepatic circulation of baicalin in rats","volume":"78","author":"Xing","year":"2005","journal-title":"Life Sci."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Shilpa, V., Shams, R., Dash, K.K., Pandey, V.K., Dar, A.H., Ayaz Mukarram, S., Hars\u00e1nyi, E., and Kov\u00e1cs, B. (2023). Phytochemical properties, extraction, and pharmacological benefits of naringin: A review. Molecules, 28.","DOI":"10.3390\/molecules28155623"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s12017-023-08771-0","article-title":"Effect of 2-Week Naringin Supplementation on Neurogenesis and BDNF Levels in Ischemia\u2013Reperfusion Model of Rats","volume":"26","author":"Yilmaz","year":"2024","journal-title":"NeuroMolecular Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"12106","DOI":"10.1007\/s12035-025-05050-w","article-title":"Effect of 2 Weeks Naringin Application on Neurological Function and Neurogenesis After Brain Ischemia\u2013Reperfusion in Ovariectomized Rats","volume":"62","author":"Keskin","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Bai, Y., Peng, W., Yang, C., Zou, W., Liu, M., Wu, H., Fan, L., Li, P., Zeng, X., and Su, W. (2020). Pharmacokinetics and Metabolism of Naringin and Active Metabolite Naringenin in Rats, Dogs, Humans, and the Differences Between Species. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00364"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Luthuli, S., Wu, S., Cheng, Y., Zheng, X., Wu, M., and Tong, H. (2019). Therapeutic effects of fucoidan: A review on recent studies. Mar. Drugs, 17.","DOI":"10.3390\/md17090487"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1007\/s00343-022-2225-8","article-title":"Pharmacokinetics of fucoidan and low molecular weight fucoidan from Saccharina japonica after oral administration to mice","volume":"41","author":"Tan","year":"2023","journal-title":"J. Oceanol. Limnol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2022.12816","article-title":"Biological and neurological activities of astaxanthin","volume":"26","author":"Si","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3164\/jcbn.10-29","article-title":"Neuroprotective Effects of Astaxanthin in Oxygen-Glucose Deprivation in SH-SY5Y Cells and Global Cerebral Ischemia in Rat","volume":"47","author":"Lee","year":"2010","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0928-0987(03)00135-0","article-title":"Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations","volume":"19","author":"Lignell","year":"2003","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1089\/ars.2010.3576","article-title":"Oxidative stress in ischemic brain damage: Mechanisms of cell death and potential molecular targets for neuroprotection","volume":"14","author":"Chen","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"698","DOI":"10.2174\/1871527311312050015","article-title":"Oxidative stress and pathophysiology of ischemic stroke: Novel therapeutic opportunities","volume":"12","author":"Rodrigo","year":"2013","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"176264","DOI":"10.1016\/j.ejphar.2023.176264","article-title":"Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2\/HO-1 signaling pathway","volume":"963","author":"Peng","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"114773","DOI":"10.1016\/j.jep.2021.114773","article-title":"Identification of potential regulating effect of baicalin on NFkappaB\/CCL2\/CCR2 signaling pathway in rats with cerebral ischemia by antibody-based array and bioinformatics analysis","volume":"284","author":"Xu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"114186","DOI":"10.1016\/j.intimp.2025.114186","article-title":"Baicalin improves neurological outcomes in mice with ischemic stroke by inhibiting astrocyte activation and neuroinflammation","volume":"149","author":"Li","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Laein, G.D., Boumeri, E., Ghanbari, S., Bagherian, A., Ahmadinasab, F., Poudineh, V., Payandeh, S., and Rashidi, N. (2025). Neuroprotective effects of berberine in preclinical models of ischemic stroke: A systematic review. BMC Pharmacol. Toxicol., 26.","DOI":"10.1186\/s40360-025-00843-0"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/s41401-018-0160-1","article-title":"Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-kappaB nuclear translocation","volume":"39","author":"Zhu","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1161\/STROKEAHA.110.608257","article-title":"Blood-brain barrier breakdown in acute and chronic cerebrovascular disease","volume":"42","author":"Yang","year":"2011","journal-title":"Stroke"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.neuron.2014.03.003","article-title":"Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke","volume":"82","author":"Knowland","year":"2014","journal-title":"Neuron"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e13006","DOI":"10.1111\/bpa.13006","article-title":"Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke","volume":"32","author":"Zhu","year":"2022","journal-title":"Brain Pathol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejphar.2006.12.028","article-title":"Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage","volume":"561","author":"Jiang","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"783","DOI":"10.3892\/etm.2021.10215","article-title":"Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood-brain barrier","volume":"22","author":"Wu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.1016\/j.biomaterials.2011.03.072","article-title":"The promotion of cerebral ischemia recovery in rats by laminin-binding BDNF","volume":"32","author":"Han","year":"2011","journal-title":"Biomaterials"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1089\/ars.2011.4459","article-title":"Mitochondrial pathways, permeability transition pore, and redox signaling in cardioprotection: Therapeutic implications","volume":"18","author":"Penna","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Yang, Y., Duan, Y., Yue, J., Yin, Y., Ma, Y., Wan, X., and Shao, J. (2025). Exosomes: An innovative therapeutic target for cerebral ischemia-reperfusion injury. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1552500"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1186\/s12967-025-06283-y","article-title":"Human neural stem cell-derived exosomes activate PINK1\/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke","volume":"23","author":"Zhao","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"786","DOI":"10.62641\/aep.v52i6.1713","article-title":"Quercetin Regulates the Polarization of Microglia through the NRF2\/HO1 Pathway and Mitigates Alzheimer\u2019s Disease","volume":"52","author":"Feng","year":"2024","journal-title":"Actas Esp. Psiquiatr."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3892\/mmr.2022.12730","article-title":"Curcumin improves the function of umbilical vein endothelial cells by inhibiting H2O2-induced pyroptosis","volume":"25","author":"Yuan","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1248\/bpb.33.1644","article-title":"Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction","volume":"33","author":"Eom","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Yu, J., Xiao, X., Chen, B., Deng, Z., Chen, X., Fan, Y., and Li, H. (2024). Synergistic and Antagonistic Activity of Selected Dietary Phytochemicals against Oxidative Stress-Induced Injury in Cardiac H9c2 Cells via the Nrf2 Signaling Pathway. Foods, 13.","DOI":"10.3390\/foods13152440"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Liu, H., Jin, X., Liu, S., Liu, X., Pei, X., Sun, K., Li, M., Wang, P., Chang, Y., and Wang, T. (2025). Recent advances in self-targeting natural product-based nanomedicines. J. Nanobiotechnology, 23.","DOI":"10.1186\/s12951-025-03092-9"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/mnfr.201100143","article-title":"Resveratrol and health--a comprehensive review of human clinical trials","volume":"55","author":"Smoliga","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/nyas.12214","article-title":"Resveratrol in mammals: Effects on aging biomarkers, age-related diseases, and life span","volume":"1290","author":"Marchal","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/03639045.2023.2252062","article-title":"ApoE-modified liposomes encapsulating resveratrol and salidroside alleviate manifestations of Alzheimer\u2019s disease in APP\/PS-1 mice","volume":"49","author":"Chen","year":"2023","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"9280","DOI":"10.1021\/jf202135j","article-title":"PLGA nanoparticles improve the oral bioavailability of curcumin in rats: Characterizations and mechanisms","volume":"59","author":"Xie","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jconrel.2023.12.030","article-title":"Erythrocyte membrane-coated nanocarriers modified by TGN for Alzheimer\u2019s disease","volume":"366","author":"Gu","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Long, Y., Liu, S., Wan, J., Zhang, Y., Li, D., Yu, S., Shi, A., Li, N., and He, F. (2023). Brain targeted borneol-baicalin liposome improves blood-brain barrier integrity after cerebral ischemia-reperfusion injury via inhibiting HIF-1\u03b1\/VEGF\/eNOS\/NO signal pathway. Biomed. Pharmacother., 160.","DOI":"10.1016\/j.biopha.2023.114240"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Long, Y., Xiang, Y., Liu, S., Zhang, Y., Wan, J., Ci, Z., Cui, M., Shen, L., Li, N., and Guan, Y. (2022). Macrophage membrane modified baicalin liposomes improve brain targeting for alleviating cerebral ischemia reperfusion injury. Nanomed. Nanotechnol. Biol. Med., 43.","DOI":"10.1016\/j.nano.2022.102547"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s00018-008-7452-4","article-title":"Curcumin: From ancient medicine to current clinical trials","volume":"65","author":"Hatcher","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1590\/0004-282x20200010","article-title":"Resveratrol in Alzheimer\u2019s disease: A review of pathophysiology and therapeutic potential","volume":"78","author":"Sousa","year":"2020","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1111\/cns.14276","article-title":"Does resveratrol improve cognition in humans? A scientometric study to an in-depth review","volume":"29","author":"Tu","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"104795","DOI":"10.1016\/j.phrs.2020.104795","article-title":"Nose to brain drug delivery-a promising strategy for active components from herbal medicine for treating cerebral ischemia reperfusion","volume":"159","author":"Long","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1007\/s12035-015-9672-6","article-title":"Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery","volume":"54","author":"Patching","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Sanchez-Navarro, M., and Giralt, E. (2022). Peptide Shuttles for Blood-Brain Barrier Drug Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091874"},{"key":"ref_153","first-page":"59","article-title":"Medicinal plants, human health and biodiversity: A broad review","volume":"147","author":"Sen","year":"2015","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Wieczorek, P.P., Hudz, N., Yezerska, O., Horcinova-Sedlackova, V., Shanaida, M., Korytniuk, O., and Jasicka-Misiak, I. (2022). Chemical Variability and Pharmacological Potential of Propolis as a Source for the Development of New Pharmaceutical Products. Molecules, 27.","DOI":"10.3390\/molecules27051600"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Maher, P. (2019). The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123056"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4155\/tde.11.153","article-title":"Nitroxide radicals and nanoparticles: A partnership for nanomedicine radical delivery","volume":"3","author":"Nagasaki","year":"2012","journal-title":"Ther. Deliv."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1089\/ars.2021.0103","article-title":"Self-Assembling Antioxidants for Ischemia-Reperfusion Injuries","volume":"36","author":"Yoshitomi","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1021\/acs.chemrev.8b00504","article-title":"Structural Simplification of Natural Products","volume":"119","author":"Wang","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/17460441.2016.1272757","article-title":"The structural modification of natural products for novel drug discovery","volume":"12","author":"Yao","year":"2017","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/ana.22553","article-title":"Evolving role of biomarkers in acute cerebrovascular disease","volume":"71","author":"Kernagis","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1161\/STROKEAHA.118.024305","article-title":"Refining Stroke and Bleeding Prediction in Atrial Fibrillation by Adding Consecutive Biomarkers to Clinical Risk Scores","volume":"50","author":"Marin","year":"2019","journal-title":"Stroke"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/9\/1153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:36:58Z","timestamp":1760035018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/9\/1153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":161,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biology14091153"],"URL":"https:\/\/doi.org\/10.3390\/biology14091153","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}