{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:37Z","timestamp":1785412537798,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"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":"crossref","award":["32472943"],"award-info":[{"award-number":["32472943"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32472943"],"award-info":[{"award-number":["32472943"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Jiangsu Modern Agricultural Industry Technology System Construction Project","award":["JATS [2023]425"],"award-info":[{"award-number":["JATS [2023]425"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Dietary protein oxidation impairs animal health, yet effective interventions remain limited. This study investigated whether quercetin (Q) supplementation protects against protein-oxidized soybean meal (OS)-induced oxidative stress and inflammatory injury in rats. A 2 \u00d7 2 factorial experiment was conducted with 48 three-week-old Sprague-Dawley rats randomly assigned to four dietary treatments (n = 12): fresh soybean meal (FS), FS + 400 mg\/kg Q, OS, and OS + 400 mg\/kg Q for 28 days. Serum biochemistry, intestinal and hepatic histology, antioxidant status, inflammatory markers, and transcriptomic pathways were analyzed. As a result, OS feeding elevated serum glucose and urea nitrogen, induced duodenal, jejunal and hepatic lesions, reduced total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) activity, glutathione (GSH) level, increased reactive oxygen species (ROS) and malondialdehyde (MDA) content (p &lt; 0.05), and increased IgG and IL-6 levels (p &lt; 0.05). Transcriptomic analysis revealed upregulation of heme biosynthesis and ROS synthesis pathways in jejunum and liver (p &lt; 0.05). Q supplementation mitigated these adverse effects by improving antioxidant status, reducing inflammatory lesions, downregulating heme and ROS pathways, and normalizing the expression of key genes (Ccl20, RT1-M2) and protein (Ccl20) in jejunum (p &lt; 0.05), and key genes (Duox1, Cyp4a2) and protein (Duox1) in liver (p &lt; 0.05). These findings demonstrate that Q alleviates OS-induced oxidative stress, inflammation, and tissue damage through the modulation of heme and ROS pathways.<\/jats:p>","DOI":"10.3390\/antiox15040504","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin Attenuates Oxidative Stress and Immune Inflammation via Modulating Heme and ROS Pathways in Rats Fed Protein-Oxidized Soybean Meal"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2873-8779","authenticated-orcid":false,"given":"Zhiyong","family":"Wang","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"Hunan Institute of Microbiology, Hunan Academy of Agricultural Sciences, Changsha 410009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6067-5778","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4178-2326","authenticated-orcid":false,"given":"Yanmin","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-338X","authenticated-orcid":false,"given":"Leli","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9193-0032","authenticated-orcid":false,"given":"Su","family":"Zhuang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.5713\/ab.24.0011","article-title":"Storage causes protein oxidation of soybean meal and affects antioxidant status, digestive performance and meat quality of broilers","volume":"37","author":"Wang","year":"2024","journal-title":"Anim. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Huang, Y., Cao, X., Liu, W., Jiang, G., and Wang, A. (2024). Effects of oxidized soybean meal and oxidized soybean oil on the muscle oxidative stability, flesh quality, amino acid profile, and fatty acid profile of Megalobrama amblycephala. Antioxidants, 13.","DOI":"10.3390\/antiox13111356"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115075","DOI":"10.1016\/j.foodres.2024.115075","article-title":"Thermal-induced interactions between soy protein isolate and malondialdehyde: Effects on protein digestibility, structure, and formation of advanced lipoxidation end products","volume":"196","author":"Ji","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3382\/ps\/pey344","article-title":"Heat-induced protein oxidation of soybean meal impairs growth performance and antioxidant status of broilers","volume":"98","author":"Lu","year":"2019","journal-title":"Poult. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"742394","DOI":"10.1016\/j.aquaculture.2025.742394","article-title":"Effects of oxidized soybean meal and oxidized soybean oil on growth, intestinal oxidative stability, inflammation, structure, digestive and absorptive capacity of Megalobrama amblycephala","volume":"603","author":"Huang","year":"2025","journal-title":"Aquaculture"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00726-021-03085-6","article-title":"Protein carbonylation in food and nutrition: A concise update","volume":"54","year":"2022","journal-title":"Amino Acids"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chiang, M.C., Tsai, T.Y., and Wang, C.J. (2023). The potential benefits of quercetin for brain health: A review of anti-inflammatory and neuroprotective mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076328"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102433","DOI":"10.1016\/j.psj.2022.102433","article-title":"Quercetin alleviates intestinal inflammation and improves intestinal functions via modulating gut microbiota composition in LPS-challenged laying hens","volume":"102","author":"Feng","year":"2023","journal-title":"Poult. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1168262","DOI":"10.1155\/2023\/1168262","article-title":"Quercetin application for Common Carp (Cyprinus carpio): I. effects on growth performance, humoral immunity, antioxidant status, immune-related genes, and resistance against heat stress","volume":"2023","author":"Armobin","year":"2023","journal-title":"Aquac. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100930","DOI":"10.1016\/j.jpha.2023.12.020","article-title":"New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation","volume":"14","author":"Zhang","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jiang, Z., Lhamo, G., Ma, M., Ye, X., Chen, J., He, Y., Xu, J., and Huang, L. (2025). Quercetin as a therapeutic agent for acute pancreatitis: A comprehensive review of antioxidant, anti-inflammatory, and immunomodulatory mechanisms. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1587314"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Alharbi, H.O.A., Alshebremi, M., Babiker, A.Y., and Rahmani, A.H. (2025). The role of quercetin, a flavonoid in the management of pathogenesis through regulation of oxidative stress, inflammation, and biological activities. Biomolecules, 15.","DOI":"10.3390\/biom15010151"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/mnfr.201000392","article-title":"Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57\/BL6J mice","volume":"55","author":"Kobori","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e70048","DOI":"10.1111\/aji.70048","article-title":"Quercetin supplementation reduces oxidative stress in the testes of wistar rats fed a high-fat diet","volume":"93","author":"Quadreli","year":"2025","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, Z., Wang, P., Zhou, Y., and Zhuang, S. (2024). Quercetin supplementation improves intestinal digestive and absorptive functions and microbiota in rats fed protein-oxidized soybean meal: Transcriptomics and microbiomics insights. Animals, 14.","DOI":"10.3390\/ani14162326"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.14202\/vetworld.2026.149-164","article-title":"Dose-dependent effects of dietary quercetin on performance, egg quality, metabolic health, and antioxidant defense in laying hens: A systematic review and meta-analysis","volume":"19","author":"Hartanto","year":"2026","journal-title":"Vet. World"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110348","DOI":"10.1016\/j.abb.2025.110348","article-title":"The impact of oxidative stress on abnormal lipid metabolism-mediated disease development","volume":"766","author":"Li","year":"2025","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mukai, E., Fujimoto, S., and Inagaki, N. (2022). Role of reactive oxygen species in glucose metabolism disorder in diabetic pancreatic \u03b2-cells. Biomolecules, 12.","DOI":"10.3390\/biom12091228"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.psj.2019.12.021","article-title":"Quercetin improves immune function in Arbor Acre broilers through activation of NF-\u03baB signaling pathway","volume":"99","author":"Yang","year":"2020","journal-title":"Poult. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"skab029","DOI":"10.1093\/jas\/skab029","article-title":"Feeding oxidized chicken byproduct meal impacts digestibility more than performance and oxidative status in nursery pigs","volume":"99","author":"Frame","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"124862","DOI":"10.1016\/j.envpol.2024.124862","article-title":"Quercetin intervention mitigates small intestinal damage and immunologic derangement induced by polystyrene nanoplastics: Insights from multi-omics analysis in mice","volume":"361","author":"Zhao","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.ajpath.2023.06.002","article-title":"Oxidative stress induced liver damage and remodeling of the liver vasculature","volume":"193","author":"Banerjee","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jare.2024.07.005","article-title":"Reveal the mechanism of hepatic oxidative stress in mice induced by photo-oxidation milk using multi-omics analysis techniques","volume":"72","author":"Tan","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.14341\/probl12561","article-title":"Full transcriptome analysis of gene expression in liver of mice in a comparative study of quercetin efficiency on two obesity models","volume":"66","author":"Trusov","year":"2020","journal-title":"Probl. Endokrinol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Guzel, A., Yunusoglu, S., Calapoglu, M., Candan, I.A., Onaran, I., Oncu, M., Ergun, O., and Oksay, T. (2021). Protective effects of quercetin on oxidative stress-induced tubular epithelial damage in the experimental rat hyperoxaluria model. Medicina, 57.","DOI":"10.3390\/medicina57060566"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Xu, D., Hu, M.J., Wang, Y.Q., and Cui, Y.L. (2019). Antioxidant activities of quercetin and its complexes for medicinal application. Molecules, 24.","DOI":"10.3390\/molecules24061123"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Merino de Paz, N., Carrillo-Palau, M., Hern\u00e1ndez-Camba, A., Abreu-Gonz\u00e1lez, P., de Vera-Gonz\u00e1lez, A., Gonz\u00e1lez-Delgado, A., Mart\u00edn-Gonz\u00e1lez, C., Gonz\u00e1lez-Gay, M.\u00c1., and Ferraz-Amaro, I. (2024). Association of serum malondialdehyde levels with lipid profile and liver function in patients with inflammatory bowel disease. Antioxidants, 13.","DOI":"10.3390\/antiox13101171"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s00204-024-03696-4","article-title":"Several lines of antioxidant defense against oxidative stress: Antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants","volume":"98","author":"Jomova","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41423-022-00902-0","article-title":"Redox regulation of the immune response","volume":"19","author":"Morris","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wen, X., Tang, L., Zhong, R., Liu, L., Chen, L., and Zhang, H. (2023). Role of mitophagy in regulating intestinal oxidative damage. Antioxidants, 12.","DOI":"10.3390\/antiox12020480"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41538-025-00629-y","article-title":"Development of an intestinal allergy model to evaluate the initial introduction of infant rice cereal","volume":"9","author":"Zhang","year":"2025","journal-title":"NPJ Sci. Food"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/1828051X.2023.2276263","article-title":"Effects of rutin supplementation on intestinal morphology, antioxidant capacity, immunity, and gut microbiota of laying hens fed a diet containing stored soybean meal","volume":"22","author":"Li","year":"2023","journal-title":"Ital. J. Anim. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1016\/j.immuni.2025.10.022","article-title":"Sequential class switching generates antigen-specific gut IgA from IgG1 B cells","volume":"58","author":"Siniscalco","year":"2025","journal-title":"Immunity"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, H., Huang, T., and Ma, Y. (2025). Mechanisms and therapeutic strategies of macrophages and neutrophils inducing ulcerative colitis progression. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1615340"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/labinvest.2014.114","article-title":"Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver","volume":"94","author":"Lei","year":"2014","journal-title":"Lab. Investig. A J. Tech. Methods Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41575-023-00771-6","article-title":"Gut-liver axis: Barriers and functional circuits","volume":"20","author":"Pabst","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Netea, M.G., Simon, A., van de Veerdonk, F., Kullberg, B.-J., Van der Meer, J.W.M., and Joosten, L.A.B. (2010). IL-1\u03b2 processing in host defense: Beyond the inflammasomes. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000661"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155865","DOI":"10.1016\/j.phymed.2024.155865","article-title":"Quercetin ameliorates atherosclerosis by inhibiting inflammation of vascular endothelial cells via Piezo1 channels","volume":"132","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100264","DOI":"10.1016\/j.mocell.2025.100264","article-title":"Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy","volume":"48","author":"Jiang","year":"2025","journal-title":"Mol. Cells"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100262","DOI":"10.1016\/j.mocell.2025.100262","article-title":"Multifaceted role of serine hydroxymethyltransferase in health and disease","volume":"48","author":"Zhang","year":"2025","journal-title":"Mol. Cells"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104248","DOI":"10.1016\/j.jff.2020.104248","article-title":"New insights in intestinal oxidative stress damage and the health intervention effects of nutrients: A review","volume":"75","author":"Wang","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, S., and Fan, Z. (2022). Effects of dietary protein restriction on colonic microbiota of finishing pigs. Animals, 13.","DOI":"10.3390\/ani13010009"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e70757","DOI":"10.1002\/fsn3.70757","article-title":"Quercetin improves lipopolysaccharide-induced septic liver injury by inhibiting the activation of ROCK\/NF-\u03baB\/NLRP3 pathway","volume":"13","author":"Xiao","year":"2025","journal-title":"Food Sci. Nutr."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/504\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:15:16Z","timestamp":1776744916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antiox15040504"],"URL":"https:\/\/doi.org\/10.3390\/antiox15040504","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]}}}