{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:16:57Z","timestamp":1790662617581,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:00:00Z","timestamp":1499299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81541072"],"award-info":[{"award-number":["81541072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson\u2019s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H2O2). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H2O2 were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H2O2 were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.<\/jats:p>","DOI":"10.3390\/molecules22071122","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T10:55:45Z","timestamp":1499338545000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Dengke","family":"Bao","sequence":"first","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingkai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nursing, NanYang Medical College, NanYang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Pang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,6]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Selective neuronal vulnerability to oxidative stress in the brain","volume":"2","author":"Wang","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.siny.2010.04.003","article-title":"Oxygen toxicity: Chemistry and biology of reactive oxygen species","volume":"15","author":"Buonocore","year":"2010","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.freeradbiomed.2007.07.001","article-title":"Reactive oxygen species and cellular oxygen sensing","volume":"43","author":"Cash","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","article-title":"Reactive oxygen species, cellular redox systems, and apoptosis","volume":"48","author":"Circu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s12017-014-8294-x","article-title":"Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson\u2019s disease","volume":"16","author":"Gaki","year":"2014","journal-title":"Neuromol. Med."},{"key":"ref_6","first-page":"3","article-title":"Oxidative stress mediates the pathogenic effect of different Alzheimer\u2019s disease risk factors","volume":"2","author":"Guglielmotto","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0014-5793(98)00367-6","article-title":"Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties","volume":"426","author":"Manach","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.foodchem.2014.06.079","article-title":"Quercetin-3-O-beta-d-glucopyranoside, a dietary flavonoid, protects PC12 cells from H2O2-induced cytotoxicity through inhibition of reactive oxygen species","volume":"167","author":"Shokoohinia","year":"2015","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.canlet.2008.03.046","article-title":"Multitargeted cancer prevention by quercetin","volume":"269","author":"Murakami","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.3892\/ijo.2014.2539","article-title":"Sulforaphane, quercetin and catechins complement each other in elimination of advanced pancreatic cancer by miR-let-7 induction and K-ras inhibition","volume":"45","author":"Appari","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3892\/mmr.2014.2734","article-title":"Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen-activated protein kinase\/extracellular signal-regulated kinase\/c-Jun N-terminal kinase signaling in multidrug-resistant leukemia K562 cells","volume":"11","author":"Chen","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/1097-4547(20001201)62:5<730::AID-JNR13>3.0.CO;2-K","article-title":"Quercetin inhibits c-fos, heat shock protein, and glial fibrillary acidic protein expression in injured astrocytes","volume":"62","author":"Wu","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.redox.2016.06.006","article-title":"Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction","volume":"9","author":"Li","year":"2016","journal-title":"Redox Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"633","DOI":"10.6026\/97320630009633","article-title":"Exploring in silico affinity of flavonoids and tannins to human fibroblast growth factorinducible14 (Fn14), a member of TNF receptor super family","volume":"9","author":"Prasad","year":"2013","journal-title":"Bioinformation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.bbagen.2013.10.024","article-title":"Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells\u2014Up regulation of Nrf2 expression and down regulation of NF-kappaB and COX-2","volume":"1840","author":"Ramyaa","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.jep.2013.12.033","article-title":"Myrsine seguinii ethanolic extract and its active component quercetin inhibit macrophage activation and peritonitis induced by LPS by targeting to Syk\/Src\/IRAK-1","volume":"151","author":"Yang","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ijpharm.2016.12.043","article-title":"Dermal quercetin lipid nanocapsules: Influence of the formulation on antioxidant activity and cellular protection against hydrogen peroxide","volume":"518","author":"Hatahet","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01616412.2016.1240393","article-title":"Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K\/Akt signaling pathway","volume":"38","author":"Du","year":"2016","journal-title":"Neurol. Res."},{"key":"ref_19","first-page":"133","article-title":"Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses","volume":"7","author":"Gholami","year":"2016","journal-title":"Vet. Res. Forum Int. Quart. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1254\/jphs.FP0070247","article-title":"Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats","volume":"104","author":"Pu","year":"2007","journal-title":"J. Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuroscience.2016.02.055","article-title":"Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus","volume":"324","author":"Sharma","year":"2016","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1476-5381.2010.00773.x","article-title":"Neuroprotective potential of CB1 receptor agonists in an in vitro model of Huntington\u2019s disease","volume":"160","author":"Scotter","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6873","DOI":"10.1523\/JNEUROSCI.0519-10.2010","article-title":"Tyk2\/STAT3 signaling mediates beta-amyloid-induced neuronal cell death: Implications in Alzheimer\u2019s disease","volume":"30","author":"Wan","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_24","first-page":"51958","article-title":"Paired whole cell recordings in organotypic hippocampal slices","volume":"91","author":"Fourie","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0165-0270(81)90003-0","article-title":"Organotypic monolayer cultures of nervous tissue","volume":"4","author":"Gahwiler","year":"1981","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.redox.2013.07.006","article-title":"Biological markers of oxidative stress: Applications to cardiovascular research and practice","volume":"1","author":"Ho","year":"2013","journal-title":"Redox Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0166-2236(97)01122-3","article-title":"Organotypic slice cultures: A technique has come of age","volume":"20","author":"Gahwiler","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.2147\/IJN.S127206","article-title":"Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia","volume":"12","author":"Pohland","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.taap.2013.09.031","article-title":"Toxicological and pharmacological concerns on oxidative stress and related diseases","volume":"273","author":"Saeidnia","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_30","first-page":"336","article-title":"Quercetin protects against chronic aluminum-induced oxidative stress and ensuing biochemical, cholinergic, and neurobehavioral impairments in rats","volume":"23","author":"Sharma","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0891-5849(01)00724-9","article-title":"Reactive oxygen species, antioxidants, and the mammalian thioredoxin system","volume":"31","author":"Nordberg","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.nut.2016.07.018","article-title":"Role of oxidative stress and antioxidants in daily nutrition and human health","volume":"33","author":"Bjorklund","year":"2017","journal-title":"Nutrition"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.abb.2007.12.008","article-title":"Comparative study of catalase-peroxidases (KatGs)","volume":"471","author":"Singh","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.bbagen.2012.11.020","article-title":"Glutathione peroxidases","volume":"1830","author":"Maiorino","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Magalingam, K.B., Radhakrishnan, A., and Haleagrahara, N. (2014). Protective effects of flavonol isoquercitrin, against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-49"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.brainres.2008.04.044","article-title":"Supplementation with a synthetic polyphenol limits oxidative stress and enhances neuronal cell viability in response to hypoxia-re-oxygenation injury","volume":"1219","author":"Duong","year":"2008","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/0394632015613039","article-title":"Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells","volume":"29","author":"Magalingam","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0891-5849(00)00302-6","article-title":"Triggering and modulation of apoptosis by oxidative stress","volume":"29","author":"Chandra","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1007\/s11033-010-0466-7","article-title":"Aucubin modulates Bcl-2 family proteins expression and inhibits caspases cascade in H2O2-induced PC12 cells","volume":"38","author":"Xue","year":"2011","journal-title":"Mol. Biol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9038","DOI":"10.1074\/jbc.M110.198457","article-title":"Amphipathic tail-anchoring peptide and Bcl-2 homology domain-3 (BH3) peptides from Bcl-2 family proteins induce apoptosis through different mechanisms","volume":"286","author":"Ko","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2174\/1567202043362018","article-title":"Apoptosis: A key in neurodegenerative disorders","volume":"1","author":"Ekshyyan","year":"2004","journal-title":"Curr. Neurovascular Res."},{"key":"ref_42","first-page":"117","article-title":"Apoptosis regulators","volume":"7","author":"Harada","year":"2003","journal-title":"Rev. Clin. Exp. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/archneur.60.3.369","article-title":"Caspase gene expression in the brain as a function of the clinical progression of Alzheimer disease","volume":"60","author":"Pompl","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_44","first-page":"1799","article-title":"Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo","volume":"9","author":"Miyashita","year":"1994","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/neu.480260307","article-title":"Lamina-specific synaptic connections of hippocampal neurons in vitro","volume":"26","author":"Frotscher","year":"1995","journal-title":"J. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0165-0270(91)90128-M","article-title":"A simple method for organotypic cultures of nervous tissue","volume":"37","author":"Stoppini","year":"1991","journal-title":"J. Neurosci. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1042\/BJ20100208","article-title":"What does the commonly used DCF test for oxidative stress really show?","volume":"428","author":"Karlsson","year":"2010","journal-title":"Biochem. J."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/7\/1122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:41:44Z","timestamp":1760208104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/7\/1122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,6]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["molecules22071122"],"URL":"https:\/\/doi.org\/10.3390\/molecules22071122","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,6]]}}}