{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:36:30Z","timestamp":1786700190719,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Diets high in fat and refined carbohydrates reliably mimic key features of metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatic lipid accumulation, oxidative stress, and ongoing liver injury. This study evaluated the long-term, low-dose administration of Callistemon citrinus ethanolic leaf extract and its primary bioactive compounds: d-limonene, ellagic acid, gallic acid, and p-coumaric acid to prevent lipotoxicity in rats fed a high-fat\u2013sucrose diet (HFSD). Sixty male Wistar rats were randomly divided into 10 groups: normal control group, an untreated HFSD group, and eight HFSD groups treated for 23 weeks with metformin, C. citrinus extract, the individual bioactive compounds, or a mixture of these compounds. We assessed body and organ weights, liver macroscopic features, serum markers of liver injury, oxidative stress biomarkers, histopathological changes, and hepatic fatty acid profiles. HFSD feeding induced significant body weight gain, hepatomegaly, severe tissue damage, elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), glucose and triglycerides, alongside heightened hepatic oxidative stress, and altered saturated fatty acid profiles. Conversely, treatment with metformin and the natural compounds attenuated HFSD-induced liver injury to varying degrees. Improvements in histopathological severity and serum liver enzymes correlated with decreased oxidative stress biomarkers. Notably, ellagic acid, gallic acid, d-limonene, and the bioactive mixture, significantly improved hepatic fatty acid profiles, whereas p-coumaric acid exhibited more modest effects. These results demonstrate that long-term administration of low-dose treatment can successfully improve all evaluated metabolic, biochemical, and histological parameter, suggesting that modulating oxidative stress and liver lipid composition is strongly linked to the mitigation of liver injury in this experimental MAFLD model.<\/jats:p>","DOI":"10.3390\/ijms27167255","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:01Z","timestamp":1786698241000},"page":"7255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low-Dose, Long-Term Callistemon citrinus and Its Main Compounds Alter Hepatic Fatty Acid Profiles and Protect Liver Histology in Rats Fed a High-Fat\u2013Sucrose Diet"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1059-5362","authenticated-orcid":false,"given":"Luis Alberto","family":"Ayala-Ruiz","sequence":"first","affiliation":[{"name":"Facultad de Biolog\u00eda, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1310-1033","authenticated-orcid":false,"given":"Aram Josu\u00e9","family":"Garc\u00eda-Calder\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Biolog\u00eda, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3879-5446","authenticated-orcid":false,"given":"Oliver Rafid","family":"Maga\u00f1a-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Facultad de Biolog\u00eda, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"S\u00e1nchez-Orozco","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Tar\u00edmbaro 58893, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-7384","authenticated-orcid":false,"given":"Manuel","family":"L\u00f3pez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Tar\u00edmbaro 58893, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-9202","authenticated-orcid":false,"given":"Joel E.","family":"L\u00f3pez-Meza","sequence":"additional","affiliation":[{"name":"Centro Multidisciplinario de Estudios en Biotecnolog\u00eda, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Tar\u00edmbaro 58893, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-2068","authenticated-orcid":false,"given":"Asdrubal","family":"Aguilera-M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Tar\u00edmbaro 58893, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rios-Chavez","sequence":"additional","affiliation":[{"name":"Facultad de Biolog\u00eda, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2147\/HMER.S506402","article-title":"MAFLD: A comprehensive review of the link between metabolic dysfunction and cardiovascular risk","volume":"17","author":"Mostafa","year":"2025","journal-title":"Hepatic Med. Evid. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2022.0365","article-title":"Global Incidence and Prevalence of Nonalcoholic Fatty Liver Disease","volume":"29","author":"Teng","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_3","first-page":"1026","article-title":"Association of lipid profile with non-alcoholic fatty liver disease diagnosed on ultrasound","volume":"3","author":"Ravish","year":"2025","journal-title":"Natl. Board Exam. J. Med. Sci."},{"key":"ref_4","first-page":"199","article-title":"Prevalence and Clinical-Epidemiologic Characteristics of a Mexican Population with Metabolic (Dysfunction) Associated Fatty Liver Disease: An Open Population Study","volume":"88","year":"2023","journal-title":"Rev. Gastroenterol. Mex."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"518","DOI":"10.26444\/aaem\/210489","article-title":"Association between obesity and non-alcoholic fatty liver disease (NAFLD) in adults aged 18 years and above-data from NHANES 2017\u20132018","volume":"32","author":"Yao","year":"2025","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1097\/TP.0000000000002480","article-title":"Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression From NAFLD to NASH","volume":"103","author":"Pierantonelli","year":"2019","journal-title":"Transplantation"},{"key":"ref_7","first-page":"544","article-title":"Esteatosis hep\u00e1tica no alcoh\u00f3lica: Una enfermedad silente","volume":"56","year":"2019","journal-title":"Rev. Med. Inst. Mex. Seguro Soc."},{"key":"ref_8","unstructured":"(2026, February 08). Molecular Mechanisms of Hepatic Lipid Accumulation in Non-Alcoholic Fatty Liver Disease|Cellular and Molecular Life Sciences|Springer Nature Link. Available online: https:\/\/link.springer.com\/article\/10.1007\/s00018-018-2860-6."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Fern\u00e1ndez, M., Arroyo, V., Carnicero, C., Sig\u00fcenza, R., Busta, R., Mora, N., Antol\u00edn, B., Tamayo, E., Aspichueta, P., and Carnicero-Frutos, I. (2022). Role of Oxidative Stress and Lipid Peroxidation in the Pathophysiology of NAFLD. Antioxidant, 11.","DOI":"10.3390\/antiox11112217"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Klobu\u010dar, I., Hofmann, L., Habisch, H., Lechleitner, M., Klobu\u010dar, L., Trbu\u0161i\u0107, M., Pregartner, G., Berghold, A., Madl, T., and Sa\u0161a, F. (2024). Advanced Oxidation Protein Products Are Strongly Associated with the Serum Levels and Lipid Contents of Lipoprotein Subclasses in Healthy Volunteers and Patients with Metabolic Syndrome. Antioxidant, 13.","DOI":"10.3390\/antiox13030339"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1093\/jn\/130.10.2427","article-title":"Dietary Fat Modulates Serum Paraoxonase 1 Activity in Rats","volume":"130","author":"Kudchodkar","year":"2000","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18455","DOI":"10.1038\/s41598-021-97686-6","article-title":"Oxidative Stress and Cardiometabolic Biomarkers in Patients with Non-Alcoholic Fatty Liver Disease","volume":"11","author":"Klisic","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/79697","article-title":"Metformin Reverses Fatty Liver Disease in Obese, Leptin-Deficient Mice","volume":"6","author":"Lin","year":"2000","journal-title":"Nat. Med."},{"key":"ref_14","first-page":"101168","article-title":"Metformin Treatment Reverses High Fat Diet- Induced Non-Alcoholic Fatty Liver Diseases and Dyslipidemia by Stimulating Multiple Antioxidant and Anti-Inflammatory Pathways","volume":"28","author":"Yasmin","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cai, T., Song, X., Xu, X., Dong, L., Liang, S., Xin, M., Huang, Y., Zhu, L., Li, T., and Wang, X. (2024). Effects of Plant Natural Products on Metabolic-Associated Fatty Liver Disease and the Underlying Mechanisms: A Narrative Review with a Focus on the Modulation of the Gut Microbiota. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1323261"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Machado, I.F., Miranda, R.G., Dorta, D.J., Rolo, A.P., and Palmeira, C.M. (2023). Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases. Antioxidants, 12.","DOI":"10.3390\/antiox12061212"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.indcrop.2013.02.012","article-title":"Assessment of the Terpenic Profile of Callistemon citrinus (Curtis) Skeels from Mexico","volume":"46","author":"Petronilho","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113505","DOI":"10.1016\/j.biopha.2022.113505","article-title":"Role of the Major Terpenes of Callistemon Citrinus against the Oxidative Stress during a Hypercaloric Diet in Rats","volume":"153","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ortega-P\u00e9rez, L.G., Ayala-Ruiz, L.A., Maga\u00f1a-Rodr\u00edguez, O.R., Pi\u00f1\u00f3n-Simental, J.S., Aguilera-M\u00e9ndez, A., God\u00ednez-Hern\u00e1ndez, D., and Rios-Chavez, P. (2023). Development and Evaluation of Phytosomes Containing Callistemon citrinus Leaf Extract: A Preclinical Approach for the Treatment of Obesity in a Rodent Model. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092178"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Calder\u00f3n, A.J., Maga\u00f1a-Rodr\u00edguez, O.R., Ayala-Ruiz, L.A., Hern\u00e1ndez-Soto, J.A., Pi\u00f1\u00f3n-Simental, J.S., Ortega-P\u00e9rez, L.G., Aguilera-M\u00e9ndez, A., and R\u00edos-Ch\u00e1vez, P. (2025). Evaluation of Callistemon Citrinus Compounds to Reduce Brain Oxidative Stress in Rats Fed High-Fat-Sucrose Diet. Metabolites, 16.","DOI":"10.3390\/metabo16010024"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1039\/C9FO00284G","article-title":"Ellagic Acid Ameliorates AKT-Driven Hepatic Steatosis in Mice by Suppressing de Novo Lipogenesis via the AKT\/SREBP-1\/FASN Pathway","volume":"10","author":"Zhang","year":"2019","journal-title":"Food Funct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1002\/ptr.7001","article-title":"Role of Ellagic Acid for the Prevention and Treatment of Liver Diseases","volume":"35","author":"Aishwarya","year":"2021","journal-title":"Phyther. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tanaka, M., Sato, A., Kishimoto, Y., Mabashi-Asazuma, H., Kondo, K., and Iida, K. (2020). Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes. Nutrients, 12.","DOI":"10.3390\/nu12051479"},{"key":"ref_24","first-page":"240","article-title":"Gallic Acid Treats Dust-Induced NAFLD in Rats by Improving the Liver\u2019s Anti-Oxidant Capacity and Inhibiting ROS\/NF\u03ba\u03b2\/TNF\u03b1 Inflammatory Pathway","volume":"24","author":"Fanaei","year":"2021","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110881","DOI":"10.1016\/j.exger.2020.110881","article-title":"Oral Gallic Acid Improve Liver Steatosis and Metabolism Modulating Hepatic Lipogenic Markers in Obese Mice","volume":"134","author":"Sousa","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"C954","DOI":"10.1152\/ajpcell.2000.279.4.C954","article-title":"Effect of Antioxidant Protection by p -Coumaric Acid on Low-Density Lipoprotein Cholesterol Oxidation","volume":"279","author":"Zang","year":"2000","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/2251-6581-12-43","article-title":"Dietary Polyphenols as Potential Nutraceuticals in Management of Diabetes: A Review","volume":"12","author":"Bahadoran","year":"2013","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1017\/S000711450774686X","article-title":"Effect of Gallic acid on High Fat Diet-Induced Dyslipidemia, Hepatosteatosis and Oxidative Stress in Rats","volume":"98","author":"Hsu","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"K\u00e1belov\u00e1, A., Mal\u00ednsk\u00e1, H., Markov\u00e1, I., Oliyarnyk, O., Chyl\u00edkov\u00e1, B., and \u0160eda, O. (2021). Ellagic Acid Affects Metabolic and Transcriptomic Profiles and Attenuates Features of Metabolic Syndrome in Adult Male Rats. Nutrients, 13.","DOI":"10.3390\/nu13030804"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111969","DOI":"10.1016\/j.biopha.2021.111969","article-title":"Protective Effects of p-Coumaric Acid Against High-Fat Diet-Induced Metabolic Dysregulation in Mice","volume":"142","author":"Yoon","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/s41586-019-1911-y","article-title":"GDF15 Mediates the Effects of Metformin on Body Weight and Energy Balance","volume":"578","author":"Coli","year":"2020","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8364","DOI":"10.3748\/wjg.v20.i26.8364","article-title":"Experimental Models of Non-Alcoholic Fatty Liver Disease in Rats","volume":"20","author":"Kucera","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liao, J.-T., Huang, Y.-W., Hou, C.-Y., Wang, J.-J., Wu, C.-C., and Hsieh, S.-L. (2023). D-Limonene Promotes Anti-Obesity in 3T3-L1 Adipocytes and High-Calorie Diet-Induced Obese Rats by Activating the AMPK Signaling Pathway. Nutrients, 15.","DOI":"10.3390\/nu15020267"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ejphar.2014.10.044","article-title":"Gallic acid attenuates high-fat diet-fed streptozotocin-induced insulin resistance via partial agonism of PPAR\u03b3 in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K\/p-Akt signaling pathway","volume":"15","author":"Gandhi","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nguyen, L.V., Nguyen, K.D.A., Ma, C.-T., Nguyen, Q.-T., Nguyen, H.T.H., Yang, D.-J., Tran, T.L., Kim, K.W., and Doan, K.V. (2021). P-Coumaric Acid Enhances Hypothalamic Leptin Signaling and Glucose Homeostasis in Mice via Differential Effects on AMPK Activation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031431"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dettlaff-Pokora, A., and Swierczynski, J. (2026). The Molecular Mechanism of Metforin\u2019s Action on Blood Lipid Profile in Diabetic Patients. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27104635"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/hep.23719","article-title":"Hepatic Lipotoxicity and the Pathogenesis of Nonalcoholic Steatohepatitis: The Central Role of Nontriglyceride Fatty Acid Metabolites","volume":"52","year":"2010","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15539","DOI":"10.3748\/wjg.v20.i42.15539","article-title":"Histopathology of Nonalcoholic Fatty Liver Disease\/Nonalcoholic Steatohepatitis","volume":"20","author":"Takahashi","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A New Definition for Metabolic Dysfunction-Associated Fatty Liver Disease: An International Expert Consensus Statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1002\/hep.26226","article-title":"Mitochondrial Adaptations and Dysfunctions in Nonalcoholic Fatty Liver Disease","volume":"58","author":"Begriche","year":"2013","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/10408360802610878","article-title":"The Paraoxonases: Role in Human Diseases and Methodological Difficulties in Measurement","volume":"46","author":"Camps","year":"2009","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/hep.21763","article-title":"A Lipidomic Analysis of Nonalcoholic Fatty Liver Disease","volume":"46","author":"Puri","year":"2007","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1042\/CS20030326","article-title":"Increase in Long-Chain Polyunsaturated Fatty Acid N\u22126\/N\u22123 Ratio in Relation to Hepatic Steatosis in Patients with Non-Alcoholic Fatty Liver Disease","volume":"106","author":"Araya","year":"2004","journal-title":"Clin. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev-nutr-071812-161139","article-title":"Fatty Acid\u2013Regulated Transcription Factors in the Liver","volume":"33","author":"Jump","year":"2013","journal-title":"Annu. Rev. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Melnyk, S., and Hakkak, R. (2023). Effect of Metformin Treatment on Serum Metabolic Profile Changes in Lean and Obese Zucker Rat Model for Fatty Liver Disease. Biomolecule, 13.","DOI":"10.3390\/biom13081234"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Casanova, J.E., Navarro-Marquez, M., Saez-Tamayo, T., Angarita, L., Dur\u00e1n-Ag\u00fcero, S., Fuentes-Barr\u00eda, H., Berm\u00fadez, V., and Rojas-G\u00f3mez, D.M. (2025). New Perspectives on the Molecular Action of Metformin in the Context of Cellular Transduction and Adipogenesis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083690"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s10787-022-00980-6","article-title":"The Role of AMPK-Dependent pathways in Cellular and Molecular Mechanisms of Metformin: A New Perspective for Treatment and Prevention of Diseases","volume":"30","author":"Hasanvand","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chao, J., Huo, T.-I., Cheng, H.-Y., Tsai, J.-C., Liao, J.-W., Lee, M.-S., Qin, X.-M., Hsieh, M.-T., Pao, L.-H., and Peng, W.-H. (2014). Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096969"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.phrs.2015.04.008","article-title":"Ellagic Acid: Pharmacological Activities and Molecular Mechanisms Involved in Liver Protection","volume":"97","author":"Zazueta","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, H., Xi, T., Xin, X., Feng, Q., and Hu, Y. (2023). Geniposide plus Chlorogenic Acid Reverses Non-Alcoholic Steatohepatitis Via Regulation of Gut Microbiota and Bile Acid Signaling in a Mouse Model in vivo. Front. Pharmacol., 14, Erratum in Front. Pharmacol. 2025, 16, 1657343.","DOI":"10.3389\/fphar.2023.1148737"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD Development and Therapeutic Strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrgastro.2016.147","article-title":"NAFLD and Diabetes Mellitus","volume":"14","author":"Tilg","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9547613","DOI":"10.1155\/2018\/9547613","article-title":"Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease","volume":"2018","author":"Masarone","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.freeradbiomed.2011.10.003","article-title":"Role of Oxidative Stress in the Pathogenesis of Nonalcoholic Steatohepatitis","volume":"52","author":"Rolo","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hendrikx, T., and Binder, C.J. (2020). Oxidation-Specific Epitopes in Non-Alcoholic Fatty Liver Disease. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.607011"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.4254\/wjh.v7.i10.1325","article-title":"Oxidative Stress: New Insights on the Association of Non-Alcoholic Fatty Liver Disease and Atherosclerosis","volume":"7","author":"Polimeni","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Silva-Santi, L.G.D., Antunes, M.M., Caparroz-Assef, S.M., Carbonera, F., Masi, L.N., Curi, R., Visentainer, J.V., and Bazotte, R.B. (2016). Liver Fatty Acid Composition and Inflammation in Mice Fed with High-Carbohydrate Diet or High-Fat Diet. Nutrients, 8.","DOI":"10.3390\/nu8110682"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12944-020-01346-z","article-title":"A High Fat Diet with a High C18\/C16 Ratio Induced Worse Metabolic and Transcriptomic Profiles in C57BL\/6 Mice","volume":"19","author":"Wang","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"550","DOI":"10.4254\/wjh.v5.i10.550","article-title":"Lipotoxocity in the Liver","volume":"5","author":"Kereszturi","year":"2013","journal-title":"World J. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ore\u0161ansk\u00e1, K., Chomov\u00e1, M., Kubincov\u00e1, J., Tureck\u00fd, L., and \u010eurfinov\u00e1, M. (2025). Tissue-Specific Differences in Fatty Acid Content and Desaturase Activity Between the Liver and Spinal Cord of Diabetic ZDF Rats. Biology, 14.","DOI":"10.3390\/biology14091205"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Maga\u00f1a-Rodr\u00edguez, O.R., Ortega-P\u00e9rez, L.G., Garc\u00eda-Calder\u00f3n, A.J., Ayala-Ruiz, L.A., Pi\u00f1\u00f3n-Simental, J.S., Aguilera- M\u00e9ndez, A., God\u00ednez-Hern\u00e1ndez, D., and Rios-Chavez, P. (2025). Effect of Callistemon citrinus Phytosomes on Oxidative Stress in the Brains of Rats Fed a High-Fat-Fructose diet. Biomolecules, 15.","DOI":"10.3390\/biom15081129"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101728","DOI":"10.1016\/j.molmet.2023.101728","article-title":"Non-Alcoholic Fatty Liver Disease is Characterised by a Reduced Polyunsaturated Fatty Acid Transport via Free Fatty Acids and High-Density Lipoproteins (HDL)","volume":"72","author":"Mocclaro","year":"2023","journal-title":"Mol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00394-011-0182-7","article-title":"Dietary D-Limonene Alleviates Insulin Resistance and Oxidative Stress-Induced Liver Injury in High-Fat Diet and L-NAME-Treated Rats","volume":"51","author":"Jayachitra","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Rodriguez-Cuenca, S., Whyte, L., Hagen, R., Vidal-Puig, A., and Fuller, M. (2016). Stearoyl-CoA Desaturase 1 Is a Key Determinant of Membrane Lipid Composition in 3T3-L1 Adipocytes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162047"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, F., Liu, Y.Q., Wei, J.N., Wang, X.F., Li, F.Q., Tian, X.J., Li, D., Gao, Y.X., Guo, X.Z., and Li, X.Y. (2026). D-Limonene Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Inhibiting the PPAR\u03b3\/SCD-1 Pathway and Improving Lipid Metabolism Disorders. Front. Pharmacol., 17.","DOI":"10.3389\/fphar.2026.1843336"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107041","DOI":"10.1016\/j.isci.2023.107041","article-title":"Lemon-Derived Nanovesicles Achieve Antioxidant and Anti-Inflammatory Effects Activating the AhR\/Nrf2 Signaling Pathway","volume":"26","author":"Cafora","year":"2023","journal-title":"iScience"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117532","DOI":"10.1016\/j.biopha.2024.117532","article-title":"Protective Effects of Lemon Nanovesicles: Evidence of the Nrf2\/HO-1 Pathway Contribution from in Vitro Hepatocytes and in Vivo High-Fat Diet-Fed Rats","volume":"180","author":"Gasparro","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1002\/hep.32782","article-title":"CD11b + CD43 Hi Ly6C Lo Splenocyte-Derived Macrophages Exacerbate Liver Fibrosis via Spleen-Liver Axis","volume":"77","author":"Zhang","year":"2023","journal-title":"Hepatology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"158244","DOI":"10.1016\/j.phymed.2026.158244","article-title":"Limonin Mitigates Hepatic Senescence and Fibrosis in MASH Mice by Targeting STAT3 to Inhibit Galectin-3\/mTOR Signaling","volume":"156","author":"Lan","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Liang, W., Menke, A.L., Driessen, A., Koek, G.H., Lindeman, J.H., Stoop, R., Havekes, L.M., Kleemann, R., and van den Hoek, A.M. (2014). Establishment of a General NAFLD Scoring System for Rodent Models and Comparison to Human Liver Pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115922"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.plaphy.2007.01.011","article-title":"Evaluation of the 1-Methyl-2-Phenylindole Colorimetric Assay for Aldehydic Lipid Peroxidation Products in Plants: Malondialdehyde and 4-Hydroxynonenal","volume":"45","author":"Johnston","year":"2007","journal-title":"Plant Physiol. Biochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1681\/ASN.V9112082","article-title":"Decrease of Serum Paraoxonase Activity in Chronic Renal Failure","volume":"9","author":"Dantoine","year":"1998","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.cca.2012.01.038","article-title":"Improved Detection of Ad vanced Oxidation Protein Products in Plasma","volume":"413","author":"Hanasand","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A New Automated Colorimetric Method for Measuring Total Oxidant Status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"\u0160arac, I., Debeljak-Marta\u010di\u0107, J., Taki\u0107, M., Stevanovi\u0107, V., Mile\u0161evi\u0107, J., Zekovi\u0107, M., Popovi\u0107, T., Jovanovi\u0107, J., and Vidovi\u0107, N.K. (2023). Associations of Fatty Acids Composition and Estimated Desaturase Activities in Erythrocyte Phospholipids with Biochemical and Clinical Indicators of Cardiometabolic Risk in Non-Diabetic Serbian Women: The Role of Level of Adiposity. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1065578"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1017\/S0007114512005934","article-title":"Indices of Fatty Acid Desaturase Activity in Healthy Human Subjects: Effects of Different Types of Dietary Fat","volume":"110","author":"Vessby","year":"2013","journal-title":"Br. J. Nutr."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7255\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:06:37Z","timestamp":1786698397000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":79,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167255"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167255","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}