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Orientin (Ori), a natural flavonoid with hepatoprotective potential, is restricted by poor solubility and low bioavailability. Herein, a galactosylated zein nanoplatform (Ori@Gal-Zein) was engineered via the Maillard reaction, resulting in uniform spherical nanoparticles (163.3 \u00b1 2.6 nm) with high loading capacity of Ori (7.89 \u00b1 0.14%) and gastrointestinal stability. In a CDAHFD-induced NAFLD mouse model, Ori@Gal-Zein decreased hepatic triglyceride and total cholesterol accumulation, attenuated lipid peroxidation, and restored antioxidant capacity, exhibiting comparable efficacy to silybin. Moreover, lipidomics revealed decreased triglyceride, diglyceride, and ceramide levels and restored the phosphatidylcholine\/phosphatidylethanolamine ratio. Importantly, Ori@Gal-Zein remodeled gut microbiota by normalizing the Firmicutes\/Bacteroidetes ratio, decreasing Pseudomonadota proliferation, and increasing Akkermansia abundance to alleviate NAFLD, providing a selection for carbohydrate-mediated protein nanoplatform.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06959","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:02:24Z","timestamp":1790672544000},"page":"30784-30801","source":"Crossref","is-referenced-by-count":0,"title":["Engineering a Galactosylated\nZein-Orientin Nanoplatform\nfor NAFLD Alleviation via Lipid Metabolic Modulation and Gut Microbiota\nRemodeling"],"prefix":"10.1021","volume":"74","author":[{"given":"Yinger","family":"Lan","sequence":"first","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhong","family":"Jin","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Lei","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]},{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]},{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-6243","authenticated-orcid":true,"given":"Lin","family":"Lei","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalin","family":"Ran","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]},{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6133-0335","authenticated-orcid":true,"given":"Jian","family":"Ming","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]},{"name":"Southwest University , , ,","place":["Chongqing, People\u2019s Republic of China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"issue":"4","key":"2026100711064463800_cit1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global Epidemiology of NAFLD-Related\nHCC: Trends, Predictions, Risk Factors and Prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"4","key":"2026100711064463800_cit2","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology\nof nonalcoholic fatty liver disease (NAFLD)\nand nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"issue":"7","key":"2026100711064463800_cit3","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms\nof NAFLD Development and Therapeutic Strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"issue":"1","key":"2026100711064463800_cit4","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00664-z","article-title":"Heat Shock\nProteins (HSPs) in Non-Alcoholic Fatty Liver Disease (NAFLD): From\nMolecular Mechanisms to Therapeutic Avenues","volume":"12","author":"Nie","year":"2024","journal-title":"Biomark. Res."},{"key":"2026100711064463800_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104799","article-title":"The Effects of Metformin Administration on Liver Enzymes and Body\nComposition in Non-Diabetic Patients with Non-Alcoholic Fatty Liver\nDisease and\/or Non-Alcoholic Steatohepatitis: An up-to-Date Systematic\nReview and Meta-Analysis of Randomized Controlled Trials","volume":"159","author":"Jalali","year":"2020","journal-title":"Pharmacol. Res."},{"key":"2026100711064463800_cit6","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154203","article-title":"Current\nand Emerging Pharmacological Options for the Treatment of Nonalcoholic\nSteatohepatitis","volume":"111","author":"Polyzos","year":"2020","journal-title":"Metabolism"},{"key":"2026100711064463800_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155248","article-title":"Recent\nGuidelines for Non-Alcoholic Fatty Liver Disease (NAFLD)\/ Fatty Liver\nDisease (FLD): Are They Already Outdated and in Need of Supplementation?","volume":"136","author":"Valenzuela-Vallejo","year":"2022","journal-title":"Metabolism"},{"key":"2026100711064463800_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2021.101320","article-title":"Functional\nImportance of Bioactive\nCompounds of Foods with Potential Health Benefits: A Review on Recent\nTrends","volume":"43","author":"Banwo","year":"2021","journal-title":"Food Biosci."},{"issue":"11","key":"2026100711064463800_cit9","doi-asserted-by":"publisher","first-page":"17016","DOI":"10.1021\/acsnano.1c02158","article-title":"Design of Hepatic Targeted Drug Delivery\nSystems for Natural Products: Insights into Nomenclature Revision\nof Nonalcoholic Fatty Liver Disease","volume":"15","author":"Tang","year":"2021","journal-title":"ACS Nano"},{"issue":"1","key":"2026100711064463800_cit10","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4104595","article-title":"A Review\non Medicinal Properties of Orientin","volume":"2016","author":"Lam","year":"2016","journal-title":"Adv. Pharmacol.\nPharm. Sci."},{"key":"2026100711064463800_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2025.165994","article-title":"Engineered Dual-Antioxidant Nanoplatform: Lactoferrin\nPeptide-Orientin Nanoassembly Orchestrates Redox Homeostasis for Precised\nInflammatory Bowel Disease Therapy","volume":"520","author":"Ran","year":"2025","journal-title":"Chem. Eng.\nJ."},{"issue":"12","key":"2026100711064463800_cit12","doi-asserted-by":"publisher","first-page":"4197","DOI":"10.1007\/s12010-021-03670-1","article-title":"Recent Advances on Bioactive Ingredients\nof Morchella esculenta","volume":"193","author":"Wu","year":"2021","journal-title":"Appl. Biochem. 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Food Chem."},{"issue":"10","key":"2026100711064463800_cit15","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1007\/s00210-023-02472-y","article-title":"Orientin Regulates the Proliferation\nand Migration of Hepatocellular Carcinoma Cells","volume":"396","author":"Tao","year":"2023","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"issue":"3","key":"2026100711064463800_cit16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1302\/2046-3758.143.BJR-2023-0383.R2","article-title":"Orientin alleviates\nchondrocyte senescence and osteoarthritis by inhibiting PI3K\/AKT pathway","volume":"14","author":"Chen","year":"2025","journal-title":"Bone Jt. 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