{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:55:44Z","timestamp":1790873744967,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002865","name":"Chongqing Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-MSX0685"],"award-info":[{"award-number":["CSTB2023NSCQ-MSX0685"]}],"id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002865","name":"Chongqing Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["CSTB2023TIAD-KPX0101"],"award-info":[{"award-number":["CSTB2023TIAD-KPX0101"]}],"id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016834","name":"Chongqing Municipal Health Commission","doi-asserted-by":"crossref","award":["Yu Zhong Yi [2021] 16"],"award-info":[{"award-number":["Yu Zhong Yi [2021] 16"]}],"id":[{"id":"10.13039\/100016834","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chongqing Municipal Committee of Agriculture and Rural Affairs","award":["CQMAITS202409"],"award-info":[{"award-number":["CQMAITS202409"]}]},{"name":"National Key Research and Development Program of China","award":["2021YFD1601005"],"award-info":[{"award-number":["2021YFD1601005"]}]},{"name":"Chongqing Municipal Science and Technology Bureau, Chongqing Traditional Chinese Medicine Innovation Team Project","award":["Yu Zhong Yi [2022] 33"],"award-info":[{"award-number":["Yu Zhong Yi [2022] 33"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oxidative stress in intestinal epithelial cells has been increasingly recognized as a key factor in various intestinal disorders. Gastrodia elata polysaccharide-2 (GEP-2), a water-soluble polysaccharide known for its antioxidant properties, has shown potential against intestinal injury. However, its effects on intestinal epithelial cells and the molecular mechanisms involved are not yet fully understood. In this study, we established a hydrogen peroxide (H2O2)-induced oxidative stress model using human colonic epithelial cells (NCM460) to evaluate the protective effects of GEP-2. We assessed cell viability, antioxidant enzyme activities, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP). The results demonstrated that GEP-2 pretreatment significantly improved the viability of NCM460 cells subjected to H2O2 damage. Additionally, it could enhance the antioxidant defense, reduce the levels of ROS, malondialdehyde (MDA), and maintain the MMP. Transcriptomic analysis identified 169 differentially expressed genes upregulated in the glutathione metabolism. JAK-STAT pathway and downregulated in inflammation. Furthermore, it was shown that GEP-2 treatment activated the Nuclear factor erythroid 2-related factor 2 (Nrf2)\/quinone oxidoreductase 1 (NQO1)-mediated antioxidant response and promoted the Janus kinase (JAK)\/signal transducer and activator of transcription (STAT) signaling pathway. Therefore, GEP-2 exerts multi-targeted cell protection by coordinating the Nrf2\/NQO1 antioxidant axis and the JAK\/STAT survival signaling pathway, providing a theoretical basis for the development of novel antioxidants.<\/jats:p>","DOI":"10.3390\/ijms27062655","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:10:43Z","timestamp":1773655843000},"page":"2655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective Effect of Gastrodia elata Polysaccharide GEP-2 Against Oxidative Stress in Intestinal Epithelial NCM460 Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Yongjiang","family":"Yao","sequence":"first","affiliation":[{"name":"Key Laboratory of Chinese Medicinal Resource from Lingnan (Ministry of Education), School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1389-6446","authenticated-orcid":false,"given":"Xingjian","family":"Wen","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"He","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"},{"name":"Bioengineering College, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liao","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"},{"name":"Bioengineering College, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"},{"name":"Bioengineering College, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuyu","family":"Fan","sequence":"additional","affiliation":[{"name":"Bioengineering College, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liang","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"},{"name":"Bioengineering College, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Medicinal Resource from Lingnan (Ministry of Education), School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Medicinal Resource from Lingnan (Ministry of Education), School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Chongqing Academy of Chinese Materia Medica, Nanshan Road 34, Chongqing 400065, China"},{"name":"Bioengineering College, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s41419-019-2086-z","article-title":"Keep Calm: The Intestinal Barrier at the Interface of Peace and War","volume":"10","author":"Thoo","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2015.02.118","article-title":"Food-Associated Stimuli Enhance Barrier Properties of Gastrointestinal Mucus","volume":"54","author":"Yildiz","year":"2015","journal-title":"Biomaterials"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2560019","DOI":"10.1080\/19490976.2025.2560019","article-title":"Regulatory Roles of Intestinal CD4+ T Cells in Inflammation and Their Modulation by the Intestinal Microbiota","volume":"17","author":"Ma","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.freeradbiomed.2016.01.024","article-title":"Physical Exercise, Reactive Oxygen Species and Neuroprotection","volume":"98","author":"Radak","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/s41586-022-05308-6","article-title":"Identification of Environmental Factors That Promote Intestinal Inflammation","volume":"611","author":"Sanmarco","year":"2022","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.carbpol.2014.06.047","article-title":"Purification, Characterisation and Protective Effects of Polysaccharides from Alfalfa on Hepatocytes","volume":"112","author":"Wang","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"112146","DOI":"10.1016\/j.foodres.2022.112146","article-title":"Preparation, Structural Characterization and Neuroprotective Effects to against H2O2-Induced Oxidative Damage in PC12 Cells of Polysaccharides from Pleurotus Ostreatus","volume":"163","author":"Wang","year":"2023","journal-title":"Food Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0278-6915(99)00085-X","article-title":"Safety Assessment of Butylated Hydroxyanisole and Butylated Hydroxytoluene as Antioxidant Food Additives","volume":"37","author":"Williams","year":"1999","journal-title":"Food Chem. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115716","DOI":"10.1016\/j.jep.2022.115716","article-title":"Ginseng Polysaccharide Attenuates Red Blood Cells Oxidative Stress Injury by Regulating Red Blood Cells Glycolysis and Liver Gluconeogenesis","volume":"300","author":"Wang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125124","DOI":"10.1016\/j.ijbiomac.2023.125124","article-title":"Structural Characterization and In Vitro Hepatoprotective Activity of a Novel Antioxidant Polysaccharide from Fruiting Bodies of the Mushroom Pleurotus ferulae","volume":"243","author":"Muhaxi","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, H., and Ding, F. (2017). Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases. Nutrients, 9.","DOI":"10.3390\/nu9070778"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117462","DOI":"10.1016\/j.foodres.2025.117462","article-title":"Valorization and Evaluation of Acidic and Neutral Polysaccharides from Panax ginseng Processing Residues for the Mitigating Effects on Skin Aging","volume":"221","author":"Xiong","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108609","DOI":"10.1016\/j.bioorg.2025.108609","article-title":"Structural Characterization and Effect of Activating Autophagy and Regulating Oxidative Stress of Polysaccharide from Fibrous Roots of Atractylodes chinensis","volume":"162","author":"Wang","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Y., and Liu, J. (2025). Structural Characterization of, and Protective Effects Against, CoCl2-Induced Hypoxia Injury to a Novel Neutral Polysaccharide from Lycium barbarum L.. Foods, 14.","DOI":"10.3390\/foods14030339"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107383","DOI":"10.1016\/j.ultsonch.2025.107383","article-title":"Deep Eutectic Solvent Extraction of Polysaccharides from Gastrodiae elata with Ultrasonic and Enzymes Assistance: Process Optimization, Structure, and Antioxidant Activity","volume":"119","author":"Zhou","year":"2025","journal-title":"Ultrason. Sonochem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Y., and Zhao, M. (2024). Fermented Gastrodia Elata Bl. Alleviates Cognitive Deficits by Regulating Neurotransmitters and Gut Microbiota in D-Gal\/AlCl3-Induced Alzheimer\u2019s Disease-like Mice. Foods, 13.","DOI":"10.3390\/foods13132154"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116087","DOI":"10.1016\/j.foodres.2025.116087","article-title":"Probiotic-Fermented Ginger-Processed Gastrodia elata BI. Ameliorates AlCl3-Induced Cognitive Dysfunction in an Alzheimer\u2019s Disease Rat Model by Regulating the Gut Microbiota and CREB\/BDNF Pathway","volume":"207","author":"Huang","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1002\/jsfa.12491","article-title":"Effects of Polysaccharides from Gastrodia elata on the Immunomodulatory Activity and Gut Microbiota Regulation in Cyclophosphamide-treated Mice","volume":"103","author":"Li","year":"2023","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"150385","DOI":"10.1016\/j.ijbiomac.2026.150385","article-title":"Low Molecular Weight Water-Soluble Gastrodia elata Polysaccharide GEP-2 Alleviates DSS-Induced Ulcerative Colitis by Enhancing the Intestinal Barrier, Modulating Gut Microbiota, and Suppressing Inflammation","volume":"343","author":"Li","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123007","DOI":"10.1016\/j.talanta.2021.123007","article-title":"Visualization of Peroxynitrite in Cyclophosphamide-Induced Oxidative Stress by an Activatable Probe","volume":"238","author":"Li","year":"2022","journal-title":"Talanta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1248\/cpb.c22-00348","article-title":"Protective Effect of Apple Polyphenols on H2O2-Induced Oxidative Stress Damage in Human Colon Adenocarcinoma CaCO2 Cells","volume":"71","author":"Miao","year":"2023","journal-title":"Chem. Pharm. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2411320","DOI":"10.1002\/advs.202411320","article-title":"Redox-Induced Stabilization of AMBRA1 by USP7 Promotes Intestinal Oxidative Stress and Colitis Through Antagonizing DUB3-Mediated Nrf2 Deubiquitination","volume":"12","author":"Xu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sun, Y., and Wang, X. (2024). The Role of Gut Microbiota in Intestinal Disease: From an Oxidative Stress Perspective. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1328324"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.freeradbiomed.2025.03.022","article-title":"Kirenol Alleviates Cerebral Ischemia-Reperfusion Injury by Reducing Oxidative Stress and Ameliorating Mitochondrial Dysfunction via Activating the CK2\/AKT Pathway","volume":"232","author":"Zhang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2410747","DOI":"10.1002\/advs.202410747","article-title":"Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential","volume":"12","author":"Kim","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e14456","DOI":"10.1111\/cns.14456","article-title":"Neutral Polysaccharide from Gastrodia elata Alleviates Cerebral Ischemia\u2013Reperfusion Injury by Inhibiting Ferroptosis-mediated Neuroinflammation via the Nrf2\/HO-1 Signaling Pathway","volume":"30","author":"Zhang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, J.-J., and Ng, S.-C. (2022). Galangin Reverses H2O2-Induced Dermal Fibroblast Senescence via SIRT1-PGC-1\u03b1\/Nrf2 Signaling. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031387"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"144630","DOI":"10.1016\/j.ijbiomac.2025.144630","article-title":"Gastrodia elata Polysaccharide Alleviates Depression via Gut Microbiota Modulation and Keap1-Nrf2\/BDNF-TrkB Pathway Activation","volume":"317","author":"Wen","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","first-page":"1182","article-title":"Neuroprotective Effect of Polysaccharides from Gastrodia elata Blume against Corticosterone-induced Apoptosis in PC12 Cells via Inhibition of the Endoplasmic Reticulum Stress-mediated Pathway","volume":"17","author":"Zhou","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.intimp.2017.07.017","article-title":"Interleukin-10 Inhibits Neuroinflammation-Mediated Apoptosis of Ventral Mesencephalic Neurons via JAK-STAT3 Pathway","volume":"50","author":"Zhu","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116746","DOI":"10.1016\/j.jep.2023.116746","article-title":"Centella Asiatica Alleviates Psoriasis through JAK\/STAT3-Mediated Inflammation: An in Vitro and in Vivo Study","volume":"317","author":"Lin","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114385","DOI":"10.1016\/j.biopha.2023.114385","article-title":"Chaihu-Shugan-San Inhibits Neuroinflammation in the Treatment of Post-Stroke Depression through the JAK\/STAT3-GSK3\u03b2\/PTEN\/Akt Pathway","volume":"160","author":"Fan","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"JAK\/STAT3 Pathway Inhibition Blocks Skeletal Muscle Wasting Downstream of IL-6 and in Experimental Cancer Cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e54729","DOI":"10.15252\/embr.202254729","article-title":"Chronic Inflammation Decreases HSC Fitness by Activating the Druggable Jak\/Stat3 Signaling Pathway","volume":"24","author":"Grusanovic","year":"2023","journal-title":"EMBO Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2655\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:25:43Z","timestamp":1773725143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,14]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062655"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062655","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,14]]}}}