{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:04:19Z","timestamp":1784624659644,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry for Education and Research","doi-asserted-by":"publisher","award":["01ZX1903A"],"award-info":[{"award-number":["01ZX1903A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cerebral ischemia\u2013reperfusion injury is a key determinant of a poor outcome after stroke. The mitochondrial uncoupling protein 2 (UCP2) has been implicated in cerebral ischemia-reperfusion injury and in the outcome of ischemic stroke, although its role remains controversial. In C57BL\/6J and B6.129S4-Ucp2tm1Lowl\/J (UCP2\u2212\/\u2212) mice, we analyzed cognitive function and lifespan. In an MCAO model induced for one hour, infarct volumes, neurological deficits, and gene expression patterns were determined after 24 h. The UCP2 inhibitor genipin was used in an oxygen-glucose deprivation (OGD) model to investigate synaptic transmission in the hippocampus. Compared to controls, UCP2\u2212\/\u2212 mice exhibited a reduced lifespan and displayed impaired cognition. However, in 6-month-old UCP2\u2212\/\u2212 mice, the infarct volume was reduced, primarily due to a smaller core size, but not in 18-month-old animals. In both strains, ischemia induced upregulation of antioxidant defense genes, including catalase and SOD1. In the ex vivo ODG model, synaptic transmission was depressed, but pretreatment with genipin prevented the tissue from this impairment. Our findings indicate an infarct-reducing effect of UCP2 deficiency, especially in young-adult mice, and, mechanistically, a neuroprotective effect by genipin in hippocampal slices.<\/jats:p>","DOI":"10.3390\/cells15141299","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:14:27Z","timestamp":1784621667000},"page":"1299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Cerebral Infarct Volume in Young UCP2\u2212\/\u2212 Mice and Preserved Synaptic Transmission by Genipin"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7094-7644","authenticated-orcid":false,"given":"Gesine","family":"Reichart","sequence":"first","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrieke","family":"Koch","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Sellmann","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Einsle","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Mayer","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"},{"name":"Department of Human Medicine, MSH Medical School Hamburg, 20457 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8220-4570","authenticated-orcid":false,"given":"Robert","family":"Jaster","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutritional Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Kirschstein","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8782-5205","authenticated-orcid":false,"given":"Falko","family":"Lange","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-4898","authenticated-orcid":false,"given":"R\u00fcdiger","family":"K\u00f6hling","sequence":"additional","affiliation":[{"name":"Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","unstructured":"GBD 2023 Causes of Death Collaborators (2025). Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990\u20132023: A systematic analysis for the Global Burden of Disease Study 2023. Lancet, 406, 1811\u20131872."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1161\/STROKEAHA.115.012577","article-title":"Eligibility and Predictors for Acute Revascularization Procedures in a Stroke Center","volume":"47","author":"Vanacker","year":"2016","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sun, Y., Jou, E., Nguyen, T.N., Mofatteh, M., Liang, Q., Abdalkader, M., Yan, Z., Feng, M., Li, X., and Li, G. (2023). Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: A multi-center study. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1279366"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jurcau, A., and Ardelean, A.I. (2022). Oxidative Stress in Ischemia\/Reperfusion Injuries following Acute Ischemic Stroke. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030574"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","unstructured":"Wu, L., Xiong, X., Wu, X., Ye, Y., Jian, Z., Zhi, Z., and Gu, L. (2020). Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00028"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yu, Q., Zhang, Y., Wu, Y., Ma, X., and Chen, Y. (2025). Advanced Insights of Oxidative Stress in Ischemic Stroke: Pathogenesis, Diagnosis and Treatment. Neurological Problems in the Elderly\u2014Bridging Current State and New Outlooks, IntechOpen.","DOI":"10.5772\/intechopen.1009844"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fang, S., Huang, W., Qu, X., and Chai, W. (2024). The mitochondria as a potential therapeutic target in cerebral I\/R injury. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1500647"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Meng, X., Zheng, Z., Yang, L., Yang, C., Li, X., and Hao, Y. (2025). Dynamic mechanisms and targeted interventions in cerebral ischemia-reperfusion injury: Pathological cascade from ischemia to reperfusion and promising therapeutic strategies. Front. Neurosci., 19.","DOI":"10.3389\/fnins.2025.1649533"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Luo, B., Shang, T., Wei, Z., and Zou, W. (2026). Cerebral Ischemia-Reperfusion Injury: Unraveling the Mitophagy-Oxidative Stress Axis for Neuroprotective Strategies. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052448"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nesci, S., and Rubattu, S. (2024). UCP2, a Member of the Mitochondrial Uncoupling Proteins: An Overview from Physiological to Pathological Roles. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061307"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100941","DOI":"10.1016\/j.preteyeres.2021.100941","article-title":"Uncoupling proteins in the mitochondrial defense against oxidative stress","volume":"83","author":"Hass","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1800353","DOI":"10.1002\/pmic.201800353","article-title":"UCP2 Overexpression Redirects Glucose into Anabolic Metabolic Pathways","volume":"19","author":"Sreedhar","year":"2019","journal-title":"Proteomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1073\/pnas.1317400111","article-title":"UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation","volume":"111","author":"Vozza","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"148428","DOI":"10.1016\/j.bbabio.2021.148428","article-title":"Mitochondrial proton leaks and uncoupling proteins","volume":"1862","author":"Nicholls","year":"2021","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1440-1789.2007.00815.x","article-title":"Amplified expression of uncoupling proteins in human brain ischemic lesions","volume":"27","author":"Nakase","year":"2007","journal-title":"Neuropathology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8705","DOI":"10.1074\/jbc.M006938200","article-title":"Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation","volume":"276","author":"Pecqueur","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/(SICI)1096-9861(19980810)397:4<549::AID-CNE7>3.0.CO;2-1","article-title":"Distribution of the uncoupling protein 2 mRNA in the mouse brain","volume":"397","author":"Richard","year":"1998","journal-title":"J. Comp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Simon-Areces, J., Dietrich, M.O., Hermes, G., Garcia-Segura, L.M., Arevalo, M.A., and Horvath, T.L. (2012). UCP2 induced by natural birth regulates neuronal differentiation of the hippocampus and related adult behavior. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042911"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1038\/jcbfm.2010.52","article-title":"Deletion of mitochondrial uncoupling protein-2 increases ischemic brain damage after transient focal ischemia by altering gene expression patterns and enhancing inflammatory cytokines","volume":"30","author":"Haines","year":"2010","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.7150\/ijms.49849","article-title":"Deletion of mitochondrial uncoupling protein 2 exacerbates mitophagy and cell apoptosis after cerebral ischemia and reperfusion injury in mice","volume":"17","author":"He","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s12035-024-04288-0","article-title":"Mitochondrial Uncoupling Protein-2 Ameliorates Ischemic Stroke by Inhibiting Ferroptosis-Induced Brain Injury and Neuroinflammation","volume":"62","author":"Wang","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1111\/j.1471-4159.2004.02432.x","article-title":"Resistance to cerebral ischemic injury in UCP2 knockout mice: Evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels","volume":"89","author":"Arsenijevic","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cho, Y.S. (2022). Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105637"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cmet.2006.04.010","article-title":"Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets","volume":"3","author":"Zhang","year":"2006","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejphar.2018.12.028","article-title":"Genipin protects against cerebral ischemia-reperfusion injury by regulating the UCP2-SIRT3 signaling pathway","volume":"845","author":"Zhao","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"288","DOI":"10.2203\/dose-response.13-035.Ristow","article-title":"Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)","volume":"12","author":"Ristow","year":"2014","journal-title":"Dose Response"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2014.01.011","article-title":"Mitohormesis","volume":"19","author":"Yun","year":"2014","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1038\/s41598-020-62336-w","article-title":"RIPC provides neuroprotection against ischemic stroke by suppressing apoptosis via the mitochondrial pathway","volume":"10","author":"Lv","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s10495-017-1425-8","article-title":"Remote ischemic preconditioning protects human neural stem cells from oxidative stress","volume":"22","author":"Motomura","year":"2017","journal-title":"Apoptosis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1038\/s41598-023-29475-2","article-title":"Effects of different remote ischemia perconditioning methods on cerebral infarct volume and neurological impairment in rats","volume":"13","author":"Otsuka","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_32","first-page":"2908","article-title":"Ischemic Stroke and the Biological Hallmarks of Aging","volume":"16","author":"Cheng","year":"2024","journal-title":"Aging Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mito.2016.06.004","article-title":"Uncoupling protein 2 protects mice from aging","volume":"30","author":"Hirose","year":"2016","journal-title":"Mitochondrion"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s00424-025-03123-2","article-title":"Mitochondrial ATP synthase 8 single-nucleotide polymorphism affects oxidative stress and survival of mice","volume":"477","author":"Reichart","year":"2025","journal-title":"Pflug. Arch."},{"key":"ref_35","first-page":"1","article-title":"Experimental studies of ischemic brain edema","volume":"8","author":"Nakazawa","year":"1986","journal-title":"Jpn. J. Stroke"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dirnagl, U., and Members of the MCAO-SOP Group (2012). Standard operating procedures (SOP) in experimental stroke research: SOP for middle cerebral artery occlusion in the mouse. Nat. Preced.","DOI":"10.1038\/npre.2012.3492.3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible middle cerebral artery occlusion without craniectomy in rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E621","DOI":"10.1152\/ajpendo.90903.2008","article-title":"Uncoupling protein-2 regulates lifespan in mice","volume":"296","author":"Andrews","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1126\/science.1132191","article-title":"Transgenic mice with a reduced core body temperature have an increased life span","volume":"314","author":"Conti","year":"2006","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cmet.2005.01.005","article-title":"Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly","volume":"1","author":"Fridell","year":"2005","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e13214","DOI":"10.1111\/apha.13214","article-title":"Mitochondrial complex IV mutation increases reactive oxygen species production and reduces lifespan in aged mice","volume":"225","author":"Reichart","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.molmet.2016.04.002","article-title":"Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation","volume":"5","author":"Hermes","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Haines, B., and Li, P.A. (2012). Overexpression of mitochondrial uncoupling protein 2 inhibits inflammatory cytokines and activates cell survival factors after cerebral ischemia. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031739"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/nm903","article-title":"Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma","volume":"9","author":"Mattiasson","year":"2003","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2891","DOI":"10.1038\/cddis.2017.278","article-title":"Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat","volume":"8","author":"Rubattu","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.exger.2010.03.014","article-title":"How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)","volume":"45","author":"Ristow","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1111\/j.1582-4934.2008.00252.x","article-title":"The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats","volume":"12","author":"Buga","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41419-019-2219-4","article-title":"UCP2-induced hypoxia promotes lipid accumulation and tubulointerstitial fibrosis during ischemic kidney injury","volume":"11","author":"Ke","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e155475","DOI":"10.1172\/jci.insight.155475","article-title":"UCP2 modulates cardiomyocyte cell cycle activity, acetyl-CoA, and histone acetylation in response to moderate hypoxia","volume":"7","author":"Rigaud","year":"2022","journal-title":"JCI Insight"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"M\u00fcller, S., Kaiser, H., Kr\u00fcger, B., Fitzner, B., Lange, F., Bock, C.N., Nizze, H., Ibrahim, S.M., Fuellen, G., and Wolkenhauer, O. (2014). Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094494"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0022-510X(01)00557-3","article-title":"Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats","volume":"189","author":"Chen","year":"2001","journal-title":"J. Neurol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.hest.2020.09.001","article-title":"Behavioral tests in rodent models of stroke","volume":"1","author":"Ruan","year":"2020","journal-title":"Brain Hemorrhages"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1002\/1873-3468.13546","article-title":"UCP2 gene polymorphisms in obesity and diabetes, and the role of UCP2 in cancer","volume":"593","author":"Li","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sobolewska, D., Galanty, A., Grabowska, K., Makowska-W\u0105s, J., Podolak, I., and Wr\u00f3bel-Biedrawa, D. (2025). Genipin-Simple but Significant Bioactive Iridoid for Therapeutical Application and Beyond: A Review. Life, 15.","DOI":"10.3390\/life15020159"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1016\/j.bpj.2019.10.021","article-title":"Molecular Mechanisms Responsible for Pharmacological Effects of Genipin on Mitochondrial Proteins","volume":"117","author":"Kreiter","year":"2019","journal-title":"Biophys. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Jo, M.J., Jeong, S., Yun, H.K., Kim, D.Y., Kim, B.R., Kim, J.L., Na, Y.J., Park, S.H., Jeong, Y.A., and Kim, B.G. (2019). Genipin induces mitochondrial dysfunction and apoptosis via downregulation of Stat3\/mcl-1 pathway in gastric cancer. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5957-x"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101952","DOI":"10.18632\/oncotarget.21882","article-title":"Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1002\/jcb.23077","article-title":"Signal transducer and activator of transcription 3 pathway mediates genipin-induced apoptosis in U266 multiple myeloma cells","volume":"112","author":"Lee","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1093\/carcin\/bgs253","article-title":"Mitochondrial uncoupling protein 2 regulates the effects of paclitaxel on Stat3 activation and cellular survival in lung cancer cells","volume":"33","author":"Su","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/glia.22594","article-title":"Stat3 mediates LIF-induced protection of astrocytes against toxic ROS by upregulating the UPC2 mRNA pool","volume":"62","author":"Lapp","year":"2014","journal-title":"Glia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.brainres.2013.11.020","article-title":"Neuroprotection by genipin against reactive oxygen and reactive nitrogen species-mediated injury in organotypic hippocampal slice cultures","volume":"1543","author":"Hughes","year":"2014","journal-title":"Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1002\/jcb.27512","article-title":"Genipin induces cell death via intrinsic apoptosis pathways in human glioblastoma cells","volume":"120","author":"Ahani","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"20231","DOI":"10.1038\/s41598-024-71123-w","article-title":"Genipin promotes the apoptosis and autophagy of neuroblastoma cells by suppressing the PI3K\/AKT\/mTOR pathway","volume":"14","author":"Liu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1007\/s00424-015-1727-z","article-title":"UCP2 modulates single-channel properties of a MCU-dependent Ca2+ inward current in mitochondria","volume":"467","author":"Bondarenko","year":"2015","journal-title":"Pflug. Arch."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.mito.2020.10.003","article-title":"The contribution of uncoupling protein 2 to mitochondrial Ca2+ homeostasis in health and disease\u2014A short revisit","volume":"55","author":"Koshenov","year":"2020","journal-title":"Mitochondrion"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105616","DOI":"10.1016\/j.fitote.2023.105616","article-title":"Synthesis and neuroprotective effects of new genipin derivatives against glutamate-induced oxidative damage","volume":"169","author":"Luo","year":"2023","journal-title":"Fitoterapia"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:33:01Z","timestamp":1784622781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":66,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15141299"],"URL":"https:\/\/doi.org\/10.3390\/cells15141299","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}