{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T07:46:54Z","timestamp":1774079214459,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>(\u2212)-Epigallocatechin 3-gallate (EGCG) is a potent natural antioxidant, but its strong bitterness and poor palatability limit its application in animal production. This study aimed to evaluate the protective effects and underlying mechanisms of chemically synthesized EGCG derivatives against oxidative stress using a diquat-induced mouse model. A total of 36 male ICR mice were randomly assigned into six groups (n = 6): Control (T0), Diquat (T1), EGCG + Diquat (T2), Epigallocatechin octanoate (EGCO) + Diquat (T3), Epigallocatechin p-chloromethylbenzoate (EGCP) + Diquat (T4), and Epigallocatechin ibuprofen ester (EGCI) + Diquat (T5). Oxidative stress was induced by intraperitoneal injection of diquat at day 27 of the experiment, while EGCG or its derivatives were administered via dietary supplementation. At day 28, the mice were weighed, killed, and the tissues were sampled. Diquat challenge significantly impaired growth, increased serum injury markers (ALT, AST, DAO, and D-LA) (p &lt; 0.05), suppressed hepatic and jejunal antioxidant enzymes (GPx, SOD, and TAOC) while elevating MDA (p &lt; 0.05), damaged jejunal morphology (villus atrophy) (p &lt; 0.05), and downregulated tight junction proteins (ZO-1 and Occludin) (p &lt; 0.05). Chemically synthesized EGCG derivatives, especially EGCI, effectively alleviated diquat-induced growth impairment and hepatic and intestinal oxidative damage by improving intestinal barrier function and enhancing systemic antioxidant capacity, possibly in part through activation of the nuclear factor erythroid 2-related factor 2\/heme oxygenase-1 (Nrf2\/HO-1) signaling pathway. Compared with EGCG, EGCI exhibited reduced bitterness and improved palatability, which favored normal feed intake. These findings provide strong theoretical support for the future application of EGCG derivatives, especially EGCI, as functional antioxidant additives in broiler production.<\/jats:p>","DOI":"10.3390\/ani16060966","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:01Z","timestamp":1773934681000},"page":"966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EGCG Derivatives Alleviate Diquat-Induced Liver and Gut Damage in Mice by Activating an Antioxidant Pathway and Enhancing Barrier Function"],"prefix":"10.3390","volume":"16","author":[{"given":"Liting","family":"Xu","sequence":"first","affiliation":[{"name":"College of Science, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caiwei","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9365-847X","authenticated-orcid":false,"given":"Xuyang","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8985-5296","authenticated-orcid":false,"given":"Jianmin","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Science, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1080\/00439339.2019.1680025","article-title":"Genetic selection of broilers and welfare consequences: A review","volume":"76","author":"Hartcher","year":"2020","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.5713\/ajas.18.0538","article-title":"Potential crosstalk of oxidative stress and immune response in poultry through phytochemicals\u2014A review","volume":"32","author":"Lee","year":"2019","journal-title":"Asian-Australas. J. Anim. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mashkoor, J., Al-Saeed, F., Zhang, G., Alsayeqh, A., Gul, S., Hussain, R., Ahmad, L., Mustafa, R., Farooq, U., and Khan, A. (2023). Oxidative stress and toxicity produced by arsenic and chromium in broiler chicks and application of vitamin E and bentonite as ameliorating agents. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1128522"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113148","DOI":"10.1016\/j.ecoenv.2021.113148","article-title":"Total flavonoids of rhizoma drynariae protect hepatocytes against aflatoxin B1-induced oxidative stress and apoptosis in broiler chickens","volume":"230","author":"Lin","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102912","DOI":"10.1016\/j.redox.2023.102912","article-title":"Selenomethionine alleviates environmental heat stress induced hepatic lipid accumulation and glycogen infiltration of broilers via maintaining mitochondrial and endoplasmic reticulum homeostasis","volume":"67","author":"Jing","year":"2023","journal-title":"Redox Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"El-Ghareeb, W., Kishawy, A., Anter, R., Gouda, A., Abdelaziz, W., Alhawas, B., Meligy, A., Abdel-Raheem, S., Ismail, H., and Ibrahim, D. (2023). Novel antioxidant insights of myricetin on the performance of broiler chickens and alleviating experimental infection with Eimeria spp.: Crosstalk between oxidative stress and inflammation. Antioxidants, 12.","DOI":"10.3390\/antiox12051026"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103761","DOI":"10.1016\/j.psj.2024.103761","article-title":"Ethoxyquin attenuates enteric oxidative stress and inflammation by promoting cytokine expressions and symbiotic microbiota in heat-stressed broilers","volume":"103","author":"Elokil","year":"2024","journal-title":"Poult. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Eid, Y., EL-Soud, S., Gamel, M., El-Kassas, S., Azzam, M., Cerbo, A., Elolimy, A., Alagawany, M., and Kirrella, A. (2025). Dietary lysophospholipids enhance broiler performance, immune response, meat quality, and mitigate oxidative stress. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1572314"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.aninu.2023.09.001","article-title":"Plant-derived squalene supplementation improves growth performance and alleviates acute oxidative stress-induced growth retardation and intestinal damage in piglets","volume":"15","author":"Tian","year":"2023","journal-title":"Anim. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137656","DOI":"10.1016\/j.jhazmat.2025.137656","article-title":"Amino acid metabolism disorder and oxidative stress took part in EGCG alleviating Mn-caused ferroptosis via miR-9-5p\/got1 axis","volume":"489","author":"Zhou","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1742-2094-9-161","article-title":"(\u2212)-Epigallocatechin gallate inhibits endotoxin-induced expression of inflammatory cytokines in human cerebral microvascular endothelial cells","volume":"9","author":"Li","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ma, X., Ni, J., Wang, W., Zhu, Y., Zhang, Y., and Sun, M. (2024). Protective Effect of Epigallocatechin-3-gallate against Hepatic Oxidative Stress Induced by tert-Butyl Hydroperoxide in Yellow-Feathered Broilers. Antioxidants, 13.","DOI":"10.3390\/antiox13101153"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1111\/jpn.13062","article-title":"The effect of Epigallocatechin-3-gallate on small intestinal morphology, antioxidant capacity and anti-inflammatory effect in heat-stressed broilers","volume":"103","author":"Song","year":"2019","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ma, Y., Liu, G., Tang, M., Fang, J., and Jiang, H. (2021). Epigallocatechin gallate can protect mice from acute stress induced by LPS while stabilizing gut microbes and serum metabolites levels. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.640305"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.2147\/IJGM.S535716","article-title":"Identification of Potential Therapeutic Targets for Sepsis Using Mendelian Randomization and Integrated eQTL\/pQTL Analysis","volume":"18","author":"Yue","year":"2025","journal-title":"Int. J. Gen. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8241","DOI":"10.12681\/jhvms.36511","article-title":"The effect of green tea leaf on broiler\u2019s performance, blood profiles, and immunity","volume":"75","author":"Qui","year":"2025","journal-title":"J. Hell. Vet. Med. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114544","DOI":"10.1016\/j.anifeedsci.2020.114544","article-title":"Effect of different tea polyphenol products on egg production performance, egg quality and antioxidative status of laying hens","volume":"267","author":"Zhu","year":"2020","journal-title":"Anim. Feed. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3923\/ijps.2008.491.496","article-title":"Effects of green tea powder feed supplement on performance of hens in the late stage of laying","volume":"7","author":"Kojima","year":"2008","journal-title":"Int. J. Poult. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.bbrc.2011.01.079","article-title":"Evaluation of the bitterness of green tea catechins by a cell-based assay with the human bitter taste receptor hTAS2R39","volume":"405","author":"Narukawa","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1081\/CLT-100100926","article-title":"Mechanisms of toxicity, clinical features, and management of diquat poisoning: A review","volume":"38","author":"Jones","year":"2000","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lu, S., Xu, S., Chen, L., Deng, Y., and Feng, J. (2022). Periplaneta americana extract pretreatment alleviates oxidative stress and inflammation and increases the abundance of gut akkermansia muciniphila in diquat-induced Mice. Antioxidants, 11.","DOI":"10.3390\/antiox11091806"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103132","DOI":"10.1016\/j.psj.2023.103132","article-title":"Dietary curcumin supplementation alleviates diquat-induced oxidative stress in the liver of broilers","volume":"102","author":"Wu","year":"2023","journal-title":"Poult. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102479","DOI":"10.1016\/j.psj.2023.102479","article-title":"Effects of dietary supplementation with chlorogenic acid on growth performance, antioxidant capacity, and hepatic inflammation in broiler chickens subjected to diquat-induced oxidative stress","volume":"102","author":"Zha","year":"2023","journal-title":"Poult. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104997","DOI":"10.1016\/j.psj.2025.104997","article-title":"Lactobacillus reuteri alleviates diquat-induced hepatic impairment and mitochondrial dysfunction via activation of the Nrf2 antioxidant system and suppression of NF-\u03baB inflammatory response","volume":"104","author":"Zhan","year":"2025","journal-title":"Poult. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jare.2021.06.023","article-title":"Activation of Nrf2\/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress","volume":"34","author":"Zhang","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xiao, Y., Gao, X., and Yuan, J. (2024). Comparative study of an antioxidant compound and ethoxyquin on feed oxidative stability and on performance, antioxidant capacity, and intestinal health in starter broiler chickens. Antioxidants, 13.","DOI":"10.20944\/preprints202409.1166.v1"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Morsy, M., Ibrahim, Y., Hafez, S., Zenhom, N., Nair, A., Venugopala, K., Shinu, P., and Abdel-Gaber, S. (2022). Paeonol attenuates hepatic ischemia\/reperfusion injury by modulating the Nrf2\/HO-1 and TLR4\/MYD88\/NF-\u03baB signaling pathways. Antioxidants, 11.","DOI":"10.3390\/antiox11091687"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chiang, S., Chen, S., and Chang, L. (2021). The role of HO-1 and its crosstalk with oxidative stress in cancer cell survival. Cells, 10.","DOI":"10.3390\/cells10092401"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117014","DOI":"10.1016\/j.lfs.2019.117014","article-title":"Protective effects of epigallocatechin gallate against ischemia reperfusion injury in rat skeletal muscle via activating Nrf2\/HO-1 signaling pathway","volume":"239","author":"Zhao","year":"2019","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e71248","DOI":"10.1002\/fsn3.71248","article-title":"Epigallocatechin-3-Gallate mitigates atopic dermatitis-like skin lesions and psychiatric comorbidities by reducing oxidative stress","volume":"13","author":"Tang","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1016\/j.psj.2020.01.021","article-title":"Pterostilbene as a protective antioxidant attenuates diquat-induced liver injury and oxidative stress in 21-day-old broiler chickens","volume":"99","author":"Chen","year":"2020","journal-title":"Poult. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1039\/C8FO02091D","article-title":"Resveratrol improves intestinal barrier function, alleviates mitochondrial dysfunction and induces mitophagy in diquat challenged piglets1","volume":"10","author":"Cao","year":"2019","journal-title":"Food Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.freeradbiomed.2025.01.034","article-title":"CXCR3 inhibition ameliorates mitochondrial function to mitigate oxidative damage through NCOA4-mediated ferritinophagy and improves the gut microbiota in mice","volume":"229","author":"Gao","year":"2025","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e02020","DOI":"10.1016\/j.heliyon.2019.e02020","article-title":"EGCG intestinal absorption and oral bioavailability enhancement using folic acid-functionalized nanostructured lipid carriers","volume":"5","author":"Granja","year":"2019","journal-title":"Heliyon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s12974-022-02543-6","article-title":"Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain","volume":"19","author":"Peng","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1017\/S0029665110002545","article-title":"Nutritional imbalances and infections affect the thymus: Consequences on T-cell-mediated immune responses","volume":"69","author":"Savino","year":"2010","journal-title":"Proc. Nutr. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/10286020801892292","article-title":"Neuroprotection of ginsenoside Re in cerebral ischemia\u2013reperfusion injury in rats","volume":"10","author":"Chen","year":"2008","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kong, S., Li, J., Li, S., Liao, M., Li, C., Zheng, P., Guo, M., Tan, W., Zheng, Z., and Hu, Z. (2018). Anti-aging effect of chitosan oligosaccharide on d-galactose-induced subacute aging in mice. Mar. Drugs, 16.","DOI":"10.3390\/md16060181"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nong, K., Liu, Y., Fang, X., Liu, Z., and Zhang, H. (2023). Effects of the vitamin D3 on alleviating the oxidative stress induced by diquat in Wenchang chickens. Animals, 13.","DOI":"10.3390\/ani13040711"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, L., Yuan, Y., and Tao, J. (2021). Flavonoid-rich extract of paeonia lactiflora petals alleviate d-galactose-induced oxidative stress and restore gut microbiota in ICR mice. Antioxidants, 10.","DOI":"10.3390\/antiox10121889"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1017\/S0007114518000740","article-title":"Dietary l-threonine supplementation attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage of broiler chickens at an early age","volume":"119","author":"Chen","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yang, Y., Liu, L., Liu, X., Zhang, Y., Shi, H., Jia, W., Zhu, H., Jia, H., Liu, M., and Bai, X. (2020). Extracellular vesicles derived from trichinella spiralis muscle larvae ameliorate TNBS-induced colitis in mice. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01174"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1039\/D0FO00132E","article-title":"Biogenic selenium nanoparticles synthesized by Lactobacillus casei ATCC 393 alleviate diquat-induced intestinal barrier dysfunction in C57BL\/6 mice through their antioxidant activity","volume":"11","author":"Qiao","year":"2020","journal-title":"Food Funct."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101212","DOI":"10.1016\/j.redox.2019.101212","article-title":"Enhanced Keap1-Nrf2 signaling protects the myocardium from isoproterenol-induced pathological remodeling in mice","volume":"27","author":"Shanmugam","year":"2019","journal-title":"Redox Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"111994","DOI":"10.1016\/j.intimp.2024.111994","article-title":"Endotoxin tolerance ameliorates lipopolysaccharide\/D-galactosamine-induced acute liver failure by negative regulation of the NF-\u03baB\/NLRP3 and activation of Nrf2\/HO-1 via Sitr1","volume":"132","author":"Shi","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106263","DOI":"10.1016\/j.psj.2025.106263","article-title":"Sodium butyrate ameliorates lipid metabolism disorder, intestinal injury, and microbial dysbiosis in broilers under lipopolysaccharide-induced immune stress condition","volume":"105","author":"Wang","year":"2026","journal-title":"Poult. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.aninu.2025.04.020","article-title":"Mechanisms of Bacillus amyloliquefaciens on alleviating lipopolysaccharide-induced oxidative stress in broilers","volume":"24","author":"Chen","year":"2026","journal-title":"Anim. Nutr."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/6\/966\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:12:50Z","timestamp":1774069970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/6\/966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":47,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ani16060966"],"URL":"https:\/\/doi.org\/10.3390\/ani16060966","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]}}}