{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:13:58Z","timestamp":1788610438360,"version":"build-2803163510"},"reference-count":95,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Ongoing Research Funding Project, King Saud University, Riyadh, Saudi Arabia","award":["ORF-2025-84"],"award-info":[{"award-number":["ORF-2025-84"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-18477-x","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T13:39:30Z","timestamp":1759844370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aloesin activates Nrf2 signaling to attenuate obesity-associated oxidative stress and hepatic steatosis in high-fat diet-fed rats"],"prefix":"10.1038","volume":"15","author":[{"given":"Sarah M.","family":"Alamri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila Naif","family":"Al-Harbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghedeir M.","family":"Alshammari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawal A.","family":"Albadr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Abdo","family":"Yahya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"18477_CR1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1097\/CLD.0000000000000085","volume":"22","author":"M Wungjiranirun","year":"2023","unstructured":"Wungjiranirun, M., Wong, N., Jou, J. & Moylan, C. A. Updates in nonalcoholic fatty liver disease. Clin. Liver Disease. 22, 157\u2013161 (2023).","journal-title":"Clin. Liver Disease"},{"key":"18477_CR2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.12703\/r\/12-10","volume":"12","author":"E Jennison","year":"2023","unstructured":"Jennison, E. & Byrne, C. D. Recent advances in NAFLD: current areas of contention. Fac. Reviews. 12, 10 (2023).","journal-title":"Fac. Reviews"},{"key":"18477_CR3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.4103\/sjg.SJG_122_18","volume":"24","author":"K Alswat","year":"2018","unstructured":"Alswat, K. et al. Nonalcoholic fatty liver disease burden\u2013Saudi Arabia and united Arab emirates, 2017\u20132030. Saudi J. Gastroenterol. 24, 211\u2013219 (2018).","journal-title":"Saudi J. Gastroenterol."},{"key":"18477_CR4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12902-022-00980-1","volume":"22","author":"S Pouwels","year":"2022","unstructured":"Pouwels, S. et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. Disorders. 22, 63 (2022).","journal-title":"BMC Endocr. Disorders"},{"key":"18477_CR5","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","volume":"65","author":"E Buzzetti","year":"2016","unstructured":"Buzzetti, E., Pinzani, M. & Tsochatzis, E. A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 65, 1038\u20131048 (2016).","journal-title":"Metabolism"},{"key":"18477_CR6","doi-asserted-by":"publisher","first-page":"11128","DOI":"10.3390\/ijms222011128","volume":"22","author":"S Ziolkowska","year":"2021","unstructured":"Ziolkowska, S., Binienda, A., Jab\u0142kowski, M., Szemraj, J. & Czarny, P. The interplay between insulin resistance, inflammation, oxidative stress, base excision repair and metabolic syndrome in nonalcoholic fatty liver disease. Int. J. Mol. Sci. 22, 11128 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"18477_CR7","doi-asserted-by":"publisher","first-page":"595371","DOI":"10.3389\/fmed.2021.595371","volume":"8","author":"AP Delli Bovi","year":"2021","unstructured":"Delli Bovi, A. P. et al. Oxidative stress in non-alcoholic fatty liver disease. An updated mini review. Front. Med. 8, 595371 (2021).","journal-title":"Front. Med."},{"key":"18477_CR8","doi-asserted-by":"publisher","first-page":"6909","DOI":"10.3748\/wjg.v28.i48.6909","volume":"28","author":"VN Bukke","year":"2022","unstructured":"Bukke, V. N., Moola, A., Serviddio, G., Vendemiale, G. & Bellanti, F. Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease. World J. Gastroenterol. 28, 6909 (2022).","journal-title":"World J. Gastroenterol."},{"key":"18477_CR9","doi-asserted-by":"publisher","first-page":"9873","DOI":"10.1074\/jbc.M111.312694","volume":"287","author":"SK Niture","year":"2012","unstructured":"Niture, S. K. & Jaiswal, A. K. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J. Biol. Chem. 287, 9873\u20139886 (2012).","journal-title":"J. Biol. Chem."},{"key":"18477_CR10","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1016\/j.jprot.2010.03.018","volume":"73","author":"NR Kitteringham","year":"2010","unstructured":"Kitteringham, N. R. et al. Proteomic analysis of Nrf2 deficient Transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver. J. Proteom. 73, 1612\u20131631 (2010).","journal-title":"J. Proteom."},{"key":"18477_CR11","doi-asserted-by":"publisher","first-page":"G1211","DOI":"10.1152\/ajpgi.00322.2010","volume":"299","author":"J Huang","year":"2010","unstructured":"Huang, J., Tabbi-Anneni, I., Gunda, V. & Wang, L. Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism. Am. J. Physiology-Gastrointestinal Liver Physiol. 299, G1211\u2013G1221 (2010).","journal-title":"Am. J. Physiology-Gastrointestinal Liver Physiol."},{"key":"18477_CR12","doi-asserted-by":"publisher","first-page":"e1002254","DOI":"10.1371\/journal.ppat.1002254","volume":"7","author":"D Olagnier","year":"2011","unstructured":"Olagnier, D. et al. Nrf2, a PPAR\u03b3 alternative pathway to promote CD36 expression on inflammatory macrophages: implication for malaria. PLoS Pathog. 7, e1002254 (2011).","journal-title":"PLoS Pathog."},{"key":"18477_CR13","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1111\/j.1440-1746.2012.07180.x","volume":"27","author":"Y Tanaka","year":"2012","unstructured":"Tanaka, Y., Ikeda, T., Yamamoto, K., Ogawa, H. & Kamisako, T. Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2\u2010null mice. J. Gastroenterol. Hepatol. 27, 1711\u20131717 (2012).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"18477_CR14","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1042\/BJ20130863","volume":"457","author":"MH Ludtmann","year":"2014","unstructured":"Ludtmann, M. H., Angelova, P. R., Zhang, Y. & Abramov, A. Y. Dinkova-Kostova, A. T. Nrf2 affects the efficiency of mitochondrial fatty acid oxidation. Biochem. J. 457, 415\u2013424 (2014).","journal-title":"Biochem. J."},{"key":"18477_CR15","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.fct.2016.06.011","volume":"94","author":"X Wang","year":"2016","unstructured":"Wang, X., Li, C., Xu, S., Ishfaq, M. & Zhang, X. NF-E2-related factor 2 deletion facilitates hepatic fatty acids metabolism disorder induced by high-fat diet via regulating related genes in mice. Food Chem. Toxicol. 94, 186\u2013196 (2016).","journal-title":"Food Chem. Toxicol."},{"key":"18477_CR16","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.abb.2015.11.040","volume":"591","author":"SL Slocum","year":"2016","unstructured":"Slocum, S. L. et al. Keap1\/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic and lipogenic program in mice on a high-fat diet. Arch. Biochem. Biophys. 591, 57\u201365 (2016).","journal-title":"Arch. Biochem. Biophys."},{"key":"18477_CR17","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cotox.2018.12.005","volume":"13","author":"L Li","year":"2019","unstructured":"Li, L. et al. Is Nrf2-ARE a potential target in NAFLD mitigation? Curr. Opin. Toxicol. 13, 35\u201344 (2019).","journal-title":"Curr. Opin. Toxicol."},{"key":"18477_CR18","doi-asserted-by":"publisher","first-page":"3941","DOI":"10.1167\/iovs.13-11598","volume":"54","author":"Q Zhong","year":"2013","unstructured":"Zhong, Q., Mishra, M. & Kowluru, R. A. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 54, 3941\u20133948 (2013).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"18477_CR19","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.freeradbiomed.2014.07.001","volume":"75","author":"M Mishra","year":"2014","unstructured":"Mishra, M., Zhong, Q. & Kowluru, R. A. Epigenetic modifications of Nrf2-mediated glutamate\u2013cysteine ligase: implications for the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression. Free Radic. Biol. Med. 75, 129\u2013139 (2014).","journal-title":"Free Radic. Biol. Med."},{"key":"18477_CR20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.freeradbiomed.2016.12.030","volume":"103","author":"RA Kowluru","year":"2017","unstructured":"Kowluru, R. A. & Mishra, M. Epigenetic regulation of redox signaling in diabetic retinopathy: role of Nrf2. Free Radic. Biol. Med. 103, 155\u2013164 (2017).","journal-title":"Free Radic. Biol. Med."},{"key":"18477_CR21","doi-asserted-by":"publisher","first-page":"7350","DOI":"10.1074\/jbc.RA120.013093","volume":"295","author":"WP Miller","year":"2020","unstructured":"Miller, W. P. et al. The stress response protein REDD1 promotes diabetes-induced oxidative stress in the retina by Keap1-independent Nrf2 degradation. J. Biol. Chem. 295, 7350\u20137361 (2020).","journal-title":"J. Biol. Chem."},{"key":"18477_CR22","doi-asserted-by":"publisher","first-page":"G283","DOI":"10.1152\/ajpgi.00296.2009","volume":"298","author":"H Sugimoto","year":"2010","unstructured":"Sugimoto, H. et al. Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am. J. Physiology-Gastrointestinal Liver Physiol. 298, G283\u2013G294 (2010).","journal-title":"Am. J. Physiology-Gastrointestinal Liver Physiol."},{"key":"18477_CR23","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.1039\/D1FO02989D","volume":"13","author":"Z Ke","year":"2022","unstructured":"Ke, Z. et al. Tangeretin improves hepatic steatosis and oxidative stress through the Nrf2 pathway in high fat diet-induced nonalcoholic fatty liver disease mice. Food Funct. 13, 2782\u20132790 (2022).","journal-title":"Food Funct."},{"key":"18477_CR24","doi-asserted-by":"publisher","first-page":"13079","DOI":"10.3748\/wjg.v20.i36.13079","volume":"20","author":"W Tang","year":"2014","unstructured":"Tang, W., Jiang, Y. F., Ponnusamy, M. & Diallo, M. Role of Nrf2 in chronic liver disease. World J. Gastroenterology: WJG. 20, 13079 (2014).","journal-title":"World J. Gastroenterology: WJG"},{"key":"18477_CR25","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.3390\/nu15061456","volume":"15","author":"R Al-Hussan","year":"2023","unstructured":"Al-Hussan, R., Albadr, N. A., Alshammari, G. M., Almasri, S. A. & Yahya, M. A. Phloretamide prevent hepatic and pancreatic damage in diabetic male rats by modulating Nrf2 and NF-\u03baB. Nutrients 15, 1456 (2023).","journal-title":"Nutrients"},{"key":"18477_CR26","doi-asserted-by":"publisher","first-page":"4755","DOI":"10.3390\/nu15224755","volume":"15","author":"JM Al Jadani","year":"2023","unstructured":"Al Jadani, J. M. et al. Esculeogenin A, a glycan from tomato, alleviates nonalcoholic fatty liver disease in rats through hypolipidemic, antioxidant, and Anti-Inflammatory effects. Nutrients 15, 4755 (2023).","journal-title":"Nutrients"},{"key":"18477_CR27","doi-asserted-by":"publisher","first-page":"121688","DOI":"10.1016\/j.lfs.2023.121688","volume":"322","author":"AE Farage","year":"2023","unstructured":"Farage, A. E. et al. Betulin prevents high fat diet-induced non-alcoholic fatty liver disease by mitigating oxidative stress and upregulating Nrf2 and SIRT1 in rats. Life Sci. 322, 121688 (2023).","journal-title":"Life Sci."},{"key":"18477_CR28","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.jhep.2020.09.037","volume":"74","author":"A Mohs","year":"2021","unstructured":"Mohs, A. et al. Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis. J. Hepatol. 74, 638\u2013648 (2021).","journal-title":"J. Hepatol."},{"key":"18477_CR29","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s42003-024-06243-0","volume":"7","author":"Y Wang","year":"2024","unstructured":"Wang, Y. et al. Activation of Nrf2\/HO-1 signaling pathway exacerbates cholestatic liver injury. Commun. Biology. 7, 621 (2024).","journal-title":"Commun. Biology"},{"key":"18477_CR30","doi-asserted-by":"publisher","first-page":"107155","DOI":"10.1016\/j.phrs.2024.107155","volume":"203","author":"C Tian","year":"2024","unstructured":"Tian, C., Huang, R. & Xiang, M. SIRT1: Harnessing multiple pathways to hinder NAFLD. Pharmacol. Res. 203, 107155 (2024).","journal-title":"Pharmacol. Res."},{"key":"18477_CR31","doi-asserted-by":"crossref","unstructured":"Simental-Mend\u00eda, L. E. et al. Beneficial effects of plant-derived natural products on non-alcoholic fatty liver disease. Pharmacological Prop. Plant-Derived Nat. Prod. Implications Hum. Health, 257\u2013272 (2021).","DOI":"10.1007\/978-3-030-64872-5_18"},{"key":"18477_CR32","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40200-015-0137-2","volume":"14","author":"S Alinejad-Mofrad","year":"2015","unstructured":"Alinejad-Mofrad, S., Foadoddini, M., Saadatjoo, S. A. & Shayesteh, M. Improvement of glucose and lipid profile status with Aloe Vera in pre-diabetic subjects: a randomized controlled-trial. J. Diabetes Metabolic Disorders. 14, 22 (2015).","journal-title":"J. Diabetes Metabolic Disorders"},{"key":"18477_CR33","unstructured":"Javaid, S. & Waheed, A. Hypoglycemic and hypotriglyceridemic effects of Aloe Vera whole leaf and sitagliptin in diabetic rats. International J. Pathology, 48\u201352 (2020)."},{"key":"18477_CR34","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3177\/jnsv.66.176","volume":"66","author":"A Tada","year":"2020","unstructured":"Tada, A. et al. Investigating anti-obesity effects by oral administration of Aloe Vera gel extract (AVGE): possible involvement in activation of brown adipose tissue (BAT). J. Nutri. Sci. Vitaminol. 66, 176\u2013184 (2020).","journal-title":"J. Nutri. Sci. Vitaminol."},{"key":"18477_CR35","doi-asserted-by":"publisher","first-page":"363","DOI":"10.4254\/wjh.v12.i7.363","volume":"12","author":"N Klaikeaw","year":"2020","unstructured":"Klaikeaw, N., Wongphoom, J., Werawatganon, D., Chayanupatkul, M. & Siriviriyakul, P. Anti-inflammatory and anti-oxidant effects of Aloe Vera in rats with non-alcoholic steatohepatitis. World J. Hepatol. 12, 363 (2020).","journal-title":"World J. Hepatol."},{"key":"18477_CR36","doi-asserted-by":"publisher","first-page":"100150","DOI":"10.1016\/j.prmcm.2022.100150","volume":"4","author":"AM Abubakar","year":"2022","unstructured":"Abubakar, A. M., Dibal, N. I., Attah, M. O. O. & Chiroma, S. M. Exploring the antioxidant effects of Aloe vera: potential role in controlling liver function and lipid profile in high fat and Fructose diet (HFFD) fed mice. Pharmacol. Research-Modern Chin. Med. 4, 100150 (2022).","journal-title":"Pharmacol. Research-Modern Chin. Med."},{"key":"18477_CR37","first-page":"48","volume":"42","author":"S Bolkent","year":"2004","unstructured":"Bolkent, S. et al. Effect of Aloe Vera (L.) burm. Fil. Leaf gel and pulp extracts on kidney in type-II diabetic rat models. Indian J. Exp. Biol. 42, 48\u201352 (2004).","journal-title":"Indian J. Exp. Biol."},{"key":"18477_CR38","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1248\/bpb.27.694","volume":"27","author":"A Can","year":"2004","unstructured":"Can, A. et al. Effect of Aloe Vera leaf gel and pulp extracts on the liver in type-II diabetic rat models. Biol. Pharm. Bull. 27, 694\u2013698 (2004).","journal-title":"Biol. Pharm. Bull."},{"key":"18477_CR39","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.3390\/molecules25061324","volume":"25","author":"M S\u00e1nchez","year":"2020","unstructured":"S\u00e1nchez, M., Gonz\u00e1lez-Burgos, E. & Iglesias, I. G\u00f3mez-Serranillos, M. P. Pharmacological update properties of Aloe Vera and its major active constituents. Molecules 25, 1324 (2020).","journal-title":"Molecules"},{"key":"18477_CR40","doi-asserted-by":"publisher","first-page":"951","DOI":"10.3390\/biology10100951","volume":"10","author":"M A\u00f1ibarro-Ortega","year":"2021","unstructured":"A\u00f1ibarro-Ortega, M. et al. Extraction of Aloesin from Aloe Vera rind using alternative green solvents: process optimization and biological activity assessment. Biology 10, 951 (2021).","journal-title":"Biology"},{"key":"18477_CR41","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1055\/s-2002-35666","volume":"68","author":"A Yagi","year":"2002","unstructured":"Yagi, A. et al. Antioxidant, free radical scavenging and anti-inflammatory effects of Aloesin derivatives in Aloe Vera. Planta Med. 68, 957\u2013960 (2002).","journal-title":"Planta Med."},{"key":"18477_CR42","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1089\/met.2012.0135","volume":"11","author":"M Yimam","year":"2013","unstructured":"Yimam, M. et al. UP780, a chromone-enriched Aloe composition improves insulin sensitivity. Metab. Syndr. Relat. Disord. 11, 267\u2013275 (2013).","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"18477_CR43","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1089\/met.2012.0066","volume":"11","author":"S Devaraj","year":"2013","unstructured":"Devaraj, S. et al. Effects of Aloe Vera supplementation in subjects with prediabetes\/metabolic syndrome. Metab. Syndr. Relat. Disord. 11, 35\u201340 (2013).","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"18477_CR44","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/1758-5996-6-61","volume":"6","author":"M Yimam","year":"2014","unstructured":"Yimam, M. et al. Blood glucose Lowering activity of Aloe based composition, UP780, in Alloxan induced insulin dependent mouse diabetes model. Diabetol. Metab. Syndr. 6, 61 (2014).","journal-title":"Diabetol. Metab. Syndr."},{"key":"18477_CR45","doi-asserted-by":"publisher","first-page":"105058","DOI":"10.1016\/j.jff.2022.105058","volume":"92","author":"MA Yahya","year":"2022","unstructured":"Yahya, M. A. et al. Isoliquiritigenin attenuates high-fat diet-induced intestinal damage by suppressing inflammation and oxidative stress and through activating Nrf2. J. Funct. Foods. 92, 105058 (2022).","journal-title":"J. Funct. Foods."},{"key":"18477_CR46","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.3390\/antiox13091098","volume":"13","author":"NS Alshareef","year":"2024","unstructured":"Alshareef, N. S., AlSedairy, S. A., Al-Harbi, L. N., Alshammari, G. M. & Yahya, M. A. Carthamus tinctorius l.(safflower) flower extract attenuates hepatic injury and steatosis in a rat model of type 2 diabetes mellitus via Nrf2-dependent hypoglycemic, antioxidant, and hypolipidemic effects. Antioxidants 13, 1098 (2024).","journal-title":"Antioxidants"},{"key":"18477_CR47","doi-asserted-by":"publisher","first-page":"28536","DOI":"10.3402\/fnr.v60.28536","volume":"60","author":"NA Roza","year":"2016","unstructured":"Roza, N. A., Possignolo, L. F., Palanch, A. C. & Gontijo, J. A. Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats. Food Nutr. Res. 60, 28536 (2016).","journal-title":"Food Nutr. Res."},{"key":"18477_CR48","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","volume":"226","author":"J Folch","year":"1957","unstructured":"Folch, J., Lees, M. & Stanley, G. S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497\u2013509 (1957).","journal-title":"J. Biol. Chem."},{"key":"18477_CR49","unstructured":"Bancroft, J. D. & Gamble, M. Theory and Practice of Histological Techniques (Elsevier health sciences, 2008)."},{"key":"18477_CR50","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1210\/clinem\/dgac660","volume":"108","author":"S Kalavalapalli","year":"2023","unstructured":"Kalavalapalli, S. et al. Adipose tissue insulin resistance predicts the severity of liver fibrosis in patients with type 2 diabetes and NAFLD. J. Clin. Endocrinol. Metabolism. 108, 1192\u20131201 (2023).","journal-title":"J. Clin. Endocrinol. Metabolism"},{"key":"18477_CR51","doi-asserted-by":"publisher","first-page":"256","DOI":"10.18632\/aging.100738","volume":"7","author":"RA van der Heijden","year":"2015","unstructured":"van der Heijden, R. A. et al. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL\/6j mice. Aging (Albany NY). 7, 256 (2015).","journal-title":"Aging (Albany NY)"},{"key":"18477_CR52","doi-asserted-by":"publisher","first-page":"59","DOI":"10.4110\/in.2011.11.1.59","volume":"11","author":"E Shin","year":"2011","unstructured":"Shin, E. et al. Dietary Aloe improves insulin sensitivity via the suppression of obesity-induced inflammation in obese mice. Immune Netw. 11, 59\u201367 (2011).","journal-title":"Immune Netw."},{"key":"18477_CR53","doi-asserted-by":"publisher","first-page":"3728","DOI":"10.3390\/foods11223728","volume":"11","author":"S Fu","year":"2022","unstructured":"Fu, S. et al. Aloe vera-fermented beverage ameliorates obesity and gut dysbiosis in high-fat-diet mice. Foods 11, 3728 (2022).","journal-title":"Foods"},{"key":"18477_CR54","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1021\/jf204465j","volume":"60","author":"E Misawa","year":"2012","unstructured":"Misawa, E. et al. Oral ingestion of Aloe Vera phytosterols alters hepatic gene expression profiles and ameliorates obesity-associated metabolic disorders in Zucker diabetic fatty rats. J. Agric. Food Chem. 60, 2799\u20132806 (2012).","journal-title":"J. Agric. Food Chem."},{"key":"18477_CR55","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00394-018-1663-8","volume":"58","author":"M Khalilpourfarshbafi","year":"2019","unstructured":"Khalilpourfarshbafi, M., Gholami, K., Murugan, D. D. & Sattar, A. Abdullah, N. A. Differential effects of dietary flavonoids on adipogenesis. Eur. J. Nutr. 58, 5\u201325 (2019).","journal-title":"Eur. J. Nutr."},{"key":"18477_CR56","doi-asserted-by":"crossref","unstructured":"Yunusoglu, O., T\u00fcrkmen, \u00d6., Berk\u00f6z, M., Y\u0131ld\u0131r\u0131m, M. & Yal\u0131n S. In vitro anti-obesity effect of Aloe Vera extract through transcription factors and lipolysis-associated genes. Eastern J. Medicine 27 (2022).","DOI":"10.5505\/ejm.2022.13285"},{"key":"18477_CR57","doi-asserted-by":"crossref","unstructured":"Jung, J. H., Hwang, S. B., Park, H. J., Jin, G. R. & Lee, B. H. Antiobesity and antidiabetic effects of Portulaca oleracea powder intake in high-fat diet\u2010induced obese C57BL\/6 mice. Evidence\u2010Based Complementary and Alternative Medicine 5587848 (2021). (2021).","DOI":"10.1155\/2021\/5587848"},{"key":"18477_CR58","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.yrtph.2011.07.005","volume":"61","author":"B Lynch","year":"2011","unstructured":"Lynch, B., Simon, R. & Roberts, A. Subchronic toxicity evaluation of Aloesin. Regul. Toxicol. Pharmacol. 61, 161\u2013171 (2011).","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"18477_CR59","doi-asserted-by":"publisher","first-page":"759","DOI":"10.3390\/ijms20030759","volume":"20","author":"A Cignarelli","year":"2019","unstructured":"Cignarelli, A. et al. Insulin and insulin receptors in adipose tissue development. Int. J. Mol. Sci. 20, 759 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"18477_CR60","doi-asserted-by":"publisher","first-page":"845","DOI":"10.2337\/db12-0584","volume":"62","author":"P Xue","year":"2013","unstructured":"Xue, P. et al. Adipose deficiency of Nrf2 in ob\/ob mice results in severe metabolic syndrome. Diabetes 62, 845\u2013854 (2013).","journal-title":"Diabetes"},{"key":"18477_CR61","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.3892\/mmr.2016.5393","volume":"14","author":"Z Liu","year":"2016","unstructured":"Liu, Z. et al. Deletion of Nrf2 leads to hepatic insulin resistance via the activation of NF-\u03baB in mice fed a high-fat diet. Mol. Med. Rep. 14, 1323\u20131331 (2016).","journal-title":"Mol. Med. Rep."},{"key":"18477_CR62","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3390\/antiox11020235","volume":"11","author":"J Guti\u00e9rrez-Cuevas","year":"2022","unstructured":"Guti\u00e9rrez-Cuevas, J. et al. The role of NRF2 in obesity-associated cardiovascular risk factors. Antioxidants 11, 235 (2022).","journal-title":"Antioxidants"},{"key":"18477_CR63","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ejphar.2009.08.022","volume":"620","author":"S Shin","year":"2009","unstructured":"Shin, S. et al. Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur. J. Pharmacol. 620, 138\u2013144 (2009).","journal-title":"Eur. J. Pharmacol."},{"key":"18477_CR64","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1007\/s00125-010-2001-8","volume":"54","author":"Z Yu","year":"2010","unstructured":"Yu, Z. et al. Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 [corrected](NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL\/6J mice. Diabetologia 54, 922\u2013934 (2010).","journal-title":"Diabetologia"},{"key":"18477_CR65","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.biopha.2016.12.082","volume":"87","author":"C Sampath","year":"2017","unstructured":"Sampath, C., Rashid, M. R., Sang, S. & Ahmedna, M. Green tea Epigallocatechin 3-gallate alleviates hyperglycemia and reduces advanced glycation end products via nrf2 pathway in mice with high fat diet-induced obesity. Biomed. Pharmacother. 87, 73\u201381 (2017).","journal-title":"Biomed. Pharmacother."},{"key":"18477_CR66","doi-asserted-by":"publisher","first-page":"104259","DOI":"10.1016\/j.phrs.2019.104259","volume":"145","author":"CY Kim","year":"2019","unstructured":"Kim, C. Y., Kang, B., Suh, H. J. & Choi, H. S. Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2\/Keap1 pathway. Pharmacol. Res. 145, 104259 (2019).","journal-title":"Pharmacol. Res."},{"key":"18477_CR67","doi-asserted-by":"publisher","first-page":"411","DOI":"10.14744\/SEMB.2018.83604","volume":"54","author":"EG Cetin","year":"2020","unstructured":"Cetin, E. G., Demir, N. & Sen, I. The relationship between insulin resistance and liver damage in non-alcoholic fatty liver patients. Med. Bull. Sisli Etfal Hosp. 54, 411 (2020).","journal-title":"Med. Bull. Sisli Etfal Hosp."},{"key":"18477_CR68","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3390\/children4080074","volume":"4","author":"M Manco","year":"2017","unstructured":"Manco, M. Insulin resistance and NAFLD: a dangerous liaison beyond the genetics. Children 4, 74 (2017).","journal-title":"Children"},{"key":"18477_CR69","doi-asserted-by":"crossref","unstructured":"Wang, Y., Nakajima, T., Gonzalez, F. J. & Tanaka, N. PPARs as metabolic regulators in the liver: lessons from liver-specific PPAR-null mice. International journal of molecular sciences 21, (2020). (2061).","DOI":"10.3390\/ijms21062061"},{"key":"18477_CR70","doi-asserted-by":"publisher","first-page":"3280","DOI":"10.3390\/biomedicines11123280","volume":"11","author":"N Li","year":"2023","unstructured":"Li, N. et al. SREBP regulation of lipid metabolism in liver disease, and therapeutic strategies. Biomedicines 11, 3280 (2023).","journal-title":"Biomedicines"},{"key":"18477_CR71","doi-asserted-by":"publisher","first-page":"332","DOI":"10.14218\/JCTH.2017.00061","volume":"6","author":"A Moslehi","year":"2018","unstructured":"Moslehi, A. & Hamidi-Zad, Z. Role of SREBPs in liver diseases: a mini-review. J. Clin. Translational Hepatol. 6, 332 (2018).","journal-title":"J. Clin. Translational Hepatol."},{"key":"18477_CR72","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1042\/CS20220572","volume":"136","author":"OO Badmus","year":"2022","unstructured":"Badmus, O. O., Hillhouse, S. A., Anderson, C. D., Hinds Jr, T. D. & Stec, D. E. Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways. Clin. Sci. 136, 1347\u20131366 (2022).","journal-title":"Clin. Sci."},{"key":"18477_CR73","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","volume":"62","author":"M Pawlak","year":"2015","unstructured":"Pawlak, M., Lefebvre, P. & Staels, B. Molecular mechanism of PPAR\u03b1 action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 62, 720\u2013733 (2015).","journal-title":"J. Hepatol."},{"key":"18477_CR74","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1186\/s13046-019-1288-7","volume":"38","author":"C Zhou","year":"2019","unstructured":"Zhou, C. et al. High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer. J. Experimental Clin. Cancer Res. 38, 302 (2019).","journal-title":"J. Experimental Clin. Cancer Res."},{"key":"18477_CR75","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.immuni.2019.06.005","volume":"51","author":"A Kusnadi","year":"2019","unstructured":"Kusnadi, A. et al. The cytokine TNF promotes transcription factor SREBP activity and binding to inflammatory genes to activate macrophages and limit tissue repair. Immunity 51, 241\u2013257 (2019). e249.","journal-title":"Immunity"},{"key":"18477_CR76","first-page":"1080","volume":"1792","author":"P Pettinelli","year":"2009","unstructured":"Pettinelli, P. et al. Enhancement in liver SREBP-1c\/PPAR-\u03b1 ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim. Et Biophys. Acta (BBA)-molecular Basis Disease. 1792, 1080\u20131086 (2009).","journal-title":"Biochim. Et Biophys. Acta (BBA)-molecular Basis Disease"},{"key":"18477_CR77","doi-asserted-by":"publisher","first-page":"113127","DOI":"10.1016\/j.biopha.2022.113127","volume":"151","author":"J Pan","year":"2022","unstructured":"Pan, J. et al. Natural PPARs agonists for the treatment of nonalcoholic fatty liver disease. Biomed. Pharmacother. 151, 113127 (2022).","journal-title":"Biomed. Pharmacother."},{"key":"18477_CR78","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1002\/ptr.5532","volume":"30","author":"R Pothuraju","year":"2016","unstructured":"Pothuraju, R., Sharma, R. K., Onteru, S. K., Singh, S. & Hussain, S. A. Hypoglycemic and hypolipidemic effects of Aloe Vera extract preparations: A review. Phytother. Res. 30, 200\u2013207 (2016).","journal-title":"Phytother. Res."},{"key":"18477_CR79","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.jff.2018.07.050","volume":"48","author":"W Rahoui","year":"2018","unstructured":"Rahoui, W. et al. Beneficial effects of Aloe Vera gel on lipid profile, lipase activities and oxidant\/antioxidant status in obese rats. J. Funct. Foods. 48, 525\u2013532 (2018).","journal-title":"J. Funct. Foods."},{"key":"18477_CR80","doi-asserted-by":"publisher","first-page":"S244","DOI":"10.1080\/10408398.2018.1496320","volume":"59","author":"Y Gao","year":"2019","unstructured":"Gao, Y., Kuok, K. I., Jin, Y. & Wang, R. Biomedical applications of Aloe Vera. Crit. Rev. Food Sci. Nutr. 59, S244\u2013S256 (2019).","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"18477_CR81","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1271\/bbb.120393","volume":"76","author":"M Saito","year":"2012","unstructured":"Saito, M. et al. Aloe Vera gel extract attenuates ethanol-induced hepatic lipid accumulation by suppressing the expression of lipogenic genes in mice. Biosci. Biotechnol. Biochem. 76, 2049\u20132054 (2012).","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"18477_CR82","doi-asserted-by":"publisher","first-page":"3585","DOI":"10.3390\/plants11243585","volume":"11","author":"TK Nguyen","year":"2022","unstructured":"Nguyen, T. K., Phung, H. H., Choi, W. J. & Ahn, H. C. Network Pharmacology and molecular Docking study on the multi-target mechanisms of Aloe Vera for non-alcoholic steatohepatitis treatment. Plants 11, 3585 (2022).","journal-title":"Plants"},{"key":"18477_CR83","first-page":"90","volume":"57","author":"S Rajasekaran","year":"2005","unstructured":"Rajasekaran, S., Sivagnanam, K. & Subramanian, S. Antioxidant effect of Aloe Vera gel extract in streptozotocin-induced diabetes in rats. Pharmacol. Rep. 57, 90\u201396 (2005).","journal-title":"Pharmacol. Rep."},{"key":"18477_CR84","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.jep.2005.10.034","volume":"103","author":"H Beppu","year":"2006","unstructured":"Beppu, H. et al. Antidiabetic effects of dietary administration of Aloe arborescens miller components on multiple low-dose streptozotocin-induced diabetes in mice: investigation on hypoglycemic action and systemic absorption dynamics of Aloe components. J. Ethnopharmacol. 103, 468\u2013477 (2006).","journal-title":"J. Ethnopharmacol."},{"key":"18477_CR85","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.2337\/diacare.27.6.1281","volume":"27","author":"TM Wolever","year":"2004","unstructured":"Wolever, T. M., Campbell, J. E., Geleva, D. & Anderson, G. H. High-fiber cereal reduces postprandial insulin responses in hyperinsulinemic but not normoinsulinemic subjects. Diabetes Care. 27, 1281\u20131285 (2004).","journal-title":"Diabetes Care"},{"key":"18477_CR86","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.fshw.2021.07.019","volume":"11","author":"R Zhong","year":"2022","unstructured":"Zhong, R. et al. Anti-diabetic effect of Aloin via JNK-IRS1\/PI3K pathways and regulation of gut microbiota. Food Sci. Hum. Wellness. 11, 189\u2013198 (2022).","journal-title":"Food Sci. Hum. Wellness"},{"key":"18477_CR87","doi-asserted-by":"publisher","first-page":"102589","DOI":"10.1016\/j.jksus.2023.102589","volume":"35","author":"NS Al-Sowayan","year":"2023","unstructured":"Al-Sowayan, N. S. & AL-Sallali, R. M. The effect of Aloin in blood glucose and antioxidants in male albino rats with Streptozoticin-induced diabetic. J. King Saud University-Science. 35, 102589 (2023).","journal-title":"J. King Saud University-Science"},{"key":"18477_CR88","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1248\/bpb.29.1418","volume":"29","author":"M Tanaka","year":"2006","unstructured":"Tanaka, M. et al. Identification of five phytosterols from Aloe Vera gel as anti-diabetic compounds. Biol. Pharm. Bull. 29, 1418\u20131422 (2006).","journal-title":"Biol. Pharm. Bull."},{"key":"18477_CR89","doi-asserted-by":"publisher","first-page":"e190","DOI":"10.1016\/j.orcp.2011.01.002","volume":"5","author":"K Nomaguchi","year":"2011","unstructured":"Nomaguchi, K. et al. Aloe Vera phytosterols act as ligands for PPAR and improve the expression levels of PPAR target genes in the livers of mice with diet-induced obesity. Obes. Res. Clin. Pract. 5, e190\u2013e201 (2011).","journal-title":"Obes. Res. Clin. Pract."},{"key":"18477_CR90","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.3748\/wjg.v24.i25.2661","volume":"24","author":"T Kanda","year":"2018","unstructured":"Kanda, T. et al. Apoptosis and non-alcoholic fatty liver diseases. World J. Gastroenterol. 24, 2661 (2018).","journal-title":"World J. Gastroenterol."},{"key":"18477_CR91","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/livers2010003","volume":"2","author":"C Smirne","year":"2022","unstructured":"Smirne, C. et al. Oxidative stress in non-alcoholic fatty liver disease. Livers 2, 30\u201376 (2022).","journal-title":"Livers"},{"key":"18477_CR92","doi-asserted-by":"publisher","first-page":"1081334","DOI":"10.3389\/fphar.2023.1081334","volume":"14","author":"C Song","year":"2023","unstructured":"Song, C., Long, X., He, J. & Huang, Y. Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease. Front. Pharmacol. 14, 1081334 (2023).","journal-title":"Front. Pharmacol."},{"key":"18477_CR93","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/antiox11010091","volume":"11","author":"Y Ma","year":"2021","unstructured":"Ma, Y., Lee, G., Heo, S. Y. & Roh, Y. S. Oxidative stress is a key modulator in the development of nonalcoholic fatty liver disease. Antioxidants 11, 91 (2021).","journal-title":"Antioxidants"},{"key":"18477_CR94","first-page":"463","volume":"42","author":"L Wu","year":"2017","unstructured":"Wu, L. & Xie, Y. Effect of NF-\u03baB on the pathogenic course of non-alcoholic fatty liver disease. Zhong Nan Da Xue Xue Bao Yi Xue ban = J. Cent. South. Univ. Med. Sci. 42, 463\u2013467 (2017).","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue ban = J. Cent. South. Univ. Med. Sci."},{"key":"18477_CR95","doi-asserted-by":"crossref","unstructured":"Park, J. S., Rustamov, N. & Roh, Y. S. The roles of NFR2-regulated oxidative stress and mitochondrial quality control in chronic liver diseases. Antioxidants 12, (2023). (1928).","DOI":"10.3390\/antiox12111928"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18477-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18477-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18477-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T15:14:13Z","timestamp":1759850053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18477-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":95,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["18477"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-18477-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"21 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34888"}}