{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:55:11Z","timestamp":1760057711806,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81872976","KJ2021ZD0061"],"award-info":[{"award-number":["81872976","KJ2021ZD0061"]}]},{"name":"Key Project of the National Science Fund of Anhui Province","award":["81872976","KJ2021ZD0061"],"award-info":[{"award-number":["81872976","KJ2021ZD0061"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Wilson\u2019s disease (WD) is an inherited disorder characterized by abnormal copper metabolism with complex pathological features. Currently, the mechanism of copper overload-induced hepatic injury is unclear. Green tea is a natural chelator, and its main ingredients, green tea polyphenol (GTP) and L-theanine (L-TA) are good at binding to heavy metals like iron and copper. There have been no reports on green tea extracts (GTE) for the treatment of Wilson\u2019s disease. This study investigated the hepatoprotective effect of GTE on WD model mice. Initially, we examined the impact of green tea extract on copper metabolism, excretion, and hepatoprotective effects in WD model toxic milk mice. Then, Ultra performance liquid chromatography (UPLC-DAD) was established to analyze GTP and L-TA in green tea extract. Further screening of eight active components and copper complex active components in green tea extract was carried out by ion analyzer. Finally, we verified the pharmacodynamic effects of these active ingredients at the animal level. The results showed that GTE improves liver function and attenuates liver injury in TX mice by promoting tissue copper excretion and inhibiting oxidative stress, which provides a theoretical basis for green tea\u2019s potential to improve the clinical symptoms of WD.<\/jats:p>","DOI":"10.3390\/foods14040679","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T11:31:17Z","timestamp":1739791877000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Copper Ion Scavenger: Investigation of the Hepatoprotective Effects of Green Tea Extract in Toxic-Milk Mice with Wilson\u2019s Disease Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Delai","family":"Yang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujuan","family":"Xuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-8035","authenticated-orcid":false,"given":"Huan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education of Xinan Medicine, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuge","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education of Xinan Medicine, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6176-9516","authenticated-orcid":false,"given":"An","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China"},{"name":"Anhui Province Key Laboratory of Research and Development of Chinese Medicine, Functional Activity and Resource Utilization on Edible and Medicinal Fungi Joint Laboratory of Anhui Province, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"ref_1","unstructured":"Immergluck, J., and Anilkumar, A.C. (2025). Wilson Disease. StatPearls, StatPearls Publishing. Disclosure: Arayamparambil Anilkumar declares no relevant financial relationships with ineligible companies."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1136\/jnnp-2021-326123","article-title":"Wilson\u2019s disease: Update on pathogenesis, biomarkers and treatments","volume":"92","author":"Shribman","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e18284","DOI":"10.1097\/MD.0000000000018284","article-title":"Relationship between genetic mutations and clinical phenotypes in patients with Wilson disease","volume":"98","author":"Zhu","year":"2019","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Himoto, T., and Masaki, T. (2020). Current Trends of Essential Trace Elements in Patients with Chronic Liver Diseases. Nutrients, 12.","DOI":"10.3390\/nu12072084"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/iub.1611","article-title":"Dynamics of the metal binding domains and regulation of the human copper transporters ATP7B and ATP7A","volume":"69","author":"Yu","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0168-8278(24)02179-2","article-title":"Progress in drug therapy of Wilson\u2019s disease","volume":"32","author":"Zhang","year":"2024","journal-title":"Chin. J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.redox.2015.07.005","article-title":"Role of NADPH oxidases in the redox biology of liver fibrosis","volume":"6","author":"Fabregat","year":"2015","journal-title":"Redox. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2147\/TACG.S79121","article-title":"Update on the clinical management of Wilson\u2019s disease","volume":"10","author":"Hedera","year":"2017","journal-title":"Appl. Clin. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.5582\/irdr.2017.01057","article-title":"Epidemiology, diagnosis, and treatment of Wilson.s disease","volume":"6","author":"Liu","year":"2017","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1074\/jbc.M111.310789","article-title":"BMPER protein is a negative regulator of hepcidin and is up-regulated in hypotransferrinemic mice","volume":"287","author":"Patel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2174\/157340610791321479","article-title":"Effects of green tea on iron accumulation and oxidative stress in livers of iron-challenged thalassemic mice","volume":"6","author":"Saewong","year":"2010","journal-title":"Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.etp.2010.09.001","article-title":"Ameliorated effects of green tea extract on lead induced liver toxicity in rats","volume":"64","author":"Mehana","year":"2012","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1271\/bbb.120598","article-title":"Green tea extract (Camellia sinensis) fermented by Lactobacillus fermentum attenuates alcohol-induced liver damage","volume":"76","author":"Park","year":"2012","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cbi.2014.06.018","article-title":"Protective effects of polyphenols-enriched extract from Huangshan Maofeng green tea against CCl4-induced liver injury in mice","volume":"220","author":"Cui","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1002\/jsfa.10347","article-title":"Black tea polyphenol theaflavin as promising antioxidant and potential copper chelator","volume":"100","author":"Sharma","year":"2020","journal-title":"J. Sci. Food Agric."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1080\/10937404.2023.2224119","article-title":"Effects of green tea polyphenols against metal-induced genotoxic damage: Underlying mechanistic pathways","volume":"26","year":"2023","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_19","unstructured":"Mandel, S., Weinreb, O., Reznichenko, L., Kalfon, L., and Amit, T. (2006). Oxidative Stress and Neuroprotection. Journal of Neural Transmission Supplementa, Springer."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.apjtb.2017.08.005","article-title":"L-theanine: A potential multifaceted natural bioactive amide as health supplement","volume":"7","author":"Rajsekhar","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104699","DOI":"10.1016\/j.jff.2021.104699","article-title":"L-theanine relieves acute alcoholic liver injury by regulating the TNF-\u03b1\/NF-\u03baB signaling pathway in C57BL\/6J mice","volume":"86","author":"Lingli","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7674","DOI":"10.1021\/acs.jafc.8b02293","article-title":"Protective Effect and Mechanism of Theanine on Lipopolysaccharide-Induced Inflammation and Acute Liver Injury in Mice","volume":"66","author":"Wang","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7751","DOI":"10.1021\/acs.jafc.2c01379","article-title":"L-Theanine Inhibits (\u2212)-Epigallocatechin-3-gallate Oxidation via Chelating Copper","volume":"70","author":"Jia","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhu, K., Zeng, H., Yue, L., Huang, J., Ouyang, J., and Liu, Z. (2024). The Protective Effects of L-Theanine against Epigallocatechin Gallate-Induced Acute Liver Injury in Mice. Foods, 13.","DOI":"10.3390\/foods13071121"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dong, T., Wu, M.C., Tang, L.L., Jiang, H.L., Zhou, P., Kuang, C.J., Tian, L.W., and Yang, W.M. (2021). GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson\u2019s disease. Biosci. Rep., 41.","DOI":"10.1042\/BSR20202717"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1101\/gad.314658.118","article-title":"DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of Wilson\u2019s disease","volume":"32","author":"Krishnan","year":"2018","journal-title":"Genes Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8803","DOI":"10.1074\/jbc.M114.627414","article-title":"Communication between the N and C termini is required for copper-stimulated Ser\/Thr phosphorylation of Cu(I)-ATPase (ATP7B)","volume":"290","author":"Braiterman","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/hep.22261","article-title":"Diagnosis and treatment of Wilson disease: An update","volume":"47","author":"Roberts","year":"2008","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1172\/JCI45401","article-title":"Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease","volume":"121","author":"Zischka","year":"2011","journal-title":"J. Clin. Invest."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.4254\/wjh.v7.i29.2859","article-title":"Wilson\u2019s disease: A review of what we have learned","volume":"7","author":"Sturniolo","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s10534-018-0153-z","article-title":"Protective effect of tea against lead and cadmium-induced oxidative stress-a review","volume":"31","year":"2018","journal-title":"Biometals"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1039\/C1FO10086F","article-title":"Reactions of green and black teas with Cu(II)","volume":"3","author":"Goodman","year":"2012","journal-title":"Food Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cca.2018.11.034","article-title":"Misclassification of chronic hepatitis B natural history phase: Insight from new ALT, AST, AKP, and GGT reference intervals in Chinese children","volume":"489","author":"Chang","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jbspin.2007.02.002","article-title":"Reactive oxygen species and superoxide dismutases: Role in joint diseases","volume":"74","author":"Afonso","year":"2007","journal-title":"Jt. Bone Spine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1021\/jf502990n","article-title":"Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress","volume":"63","author":"Ding","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/ptr.6637","article-title":"Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials","volume":"34","author":"Mahmoodi","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108628","DOI":"10.1016\/j.foodres.2019.108628","article-title":"Green tea polyphenols and epigallocatechin-3-gallate protect against perfluorodecanoic acid induced liver damage and inflammation in mice by inhibiting NLRP3 inflammasome activation","volume":"127","author":"Wang","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1080\/10408398.2015.1016141","article-title":"L-theanine, unique amino acid of tea, and its metabolism, health effects, and safety","volume":"57","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cao, J., Han, J., Xiao, H., Qiao, J., and Han, M. (2016). Effect of Tea Polyphenol Compounds on Anticancer Drugs in Terms of Anti-Tumor Activity, Toxicology, and Pharmacokinetics. Nutrients, 8.","DOI":"10.3390\/nu8120762"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2696432","DOI":"10.1155\/2020\/2696432","article-title":"Green Tea Polyphenols Protect against Acetaminophen-Induced Liver Injury by Regulating the Drug Metabolizing Enzymes and Transporters","volume":"2020","author":"Lv","year":"2020","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1248\/bpb.28.1702","article-title":"Effects of theanine on alcohol metabolism and hepatic toxicity","volume":"28","author":"Sadzuka","year":"2005","journal-title":"Biol. Pharm. Bull."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/4\/679\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:36:02Z","timestamp":1760027762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/4\/679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["foods14040679"],"URL":"https:\/\/doi.org\/10.3390\/foods14040679","relation":{},"ISSN":["2304-8158"],"issn-type":[{"type":"electronic","value":"2304-8158"}],"subject":[],"published":{"date-parts":[[2025,2,17]]}}}