{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:37:19Z","timestamp":1790393839173,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Deanship of Graduate Studies and Scientific research at Jouf University","award":["DGSSR-2023-01-02423"],"award-info":[{"award-number":["DGSSR-2023-01-02423"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This study aimed to evaluate the preventive effects of geraniol on non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet (HFD) in a rat model, focusing on its impact on lipid metabolism, oxidative stress, and inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>NAFLD was induced in male Sprague\u2013Dawley rats by feeding them a HFD for 10\u00a0weeks. Geraniol was administered orally at doses of 50, 100, and 200\u00a0mg\/kg. The following parameters were assessed: body weight, hepatic index, lipid profile (total cholesterol, triglycerides, HDL, LDL), serum hepatic enzymes (ALT, AST, ALP), oxidative stress markers (MDA, SOD, CAT, GSH), and inflammatory markers (TNF-\u03b1, IL-6, IL-10). Histopathological evaluation of liver tissues was performed to assess structural changes and inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Geraniol treatment, particularly at 100 and 200\u00a0mg\/kg, significantly reduced body weight gain and hepatic index in HFD-fed rats. It improved lipid profiles by lowering total cholesterol, triglycerides, and LDL while increasing HDL levels. Hepatic enzyme levels were markedly decreased, indicating hepatoprotection. Geraniol also restored antioxidant enzyme activity and reduced markers of oxidative stress. Moreover, it lowered pro-inflammatory cytokines and elevated anti-inflammatory cytokines. Histopathological analysis confirmed reduced hepatic steatosis and inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Geraniol demonstrated potent protective effects against HFD-induced NAFLD in rats by improving lipid metabolism, mitigating oxidative stress, and modulating inflammatory responses. These findings support its potential as a therapeutic agent for the prevention and management of NAFLD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf053","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T13:42:50Z","timestamp":1755351770000},"page":"1439-1449","source":"Crossref","is-referenced-by-count":4,"title":["Protective role of geraniol in high fat diet-induced NAFLD: balancing lipid homeostasis, antioxidant defence, and inflammatory responses"],"prefix":"10.1093","volume":"77","author":[{"given":"Sakeena","family":"Noor","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, University of Sargodha , Sargodha 40100,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhria A","family":"Al-Joufi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Jouf University , Sakaka 72341 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambreen Malik","family":"Uttra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, University of Sargodha , Sargodha 40100,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-6889","authenticated-orcid":false,"given":"Sumera","family":"Qasim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Jouf University , Sakaka 72341 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, University of Sargodha , Sargodha 40100,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"2025100323020955500_ref1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/23808993.2022.2053285","article-title":"Non-alcoholic fatty liver disease-opportunities for personalized treatment and drug development","volume":"7","author":"Kemas","year":"2022","journal-title":"Expert Rev Precis Med Drug Dev"},{"key":"2025100323020955500_ref2","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12902-022-00980-1","article-title":"Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss","volume":"22","author":"Pouwels","year":"2022","journal-title":"BMC Endocr Disord"},{"key":"2025100323020955500_ref3","doi-asserted-by":"publisher","first-page":"963513","DOI":"10.3389\/fphys.2022.963513","article-title":"Non-alcoholic fatty liver disease\u2014a pilot study investigating early inflammatory and fibrotic biomarkers of NAFLD with alcoholic liver disease","volume":"13","author":"Watt","year":"2022","journal-title":"Front Physiol"},{"key":"2025100323020955500_ref4","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1016\/j.jhep.2021.01.045","article-title":"Diagnosis and management of secondary causes of steatohepatitis","volume":"74","author":"Liebe","year":"2021","journal-title":"J Hepatol"},{"key":"2025100323020955500_ref5","doi-asserted-by":"publisher","first-page":"101143","DOI":"10.1016\/j.molmet.2020.101143","article-title":"Metabolic drivers of non-alcoholic fatty liver disease","volume":"50","author":"Bence","year":"2021","journal-title":"Mol Metab"},{"key":"2025100323020955500_ref6","doi-asserted-by":"publisher","first-page":"3595","DOI":"10.3390\/ijms23073595","article-title":"Mitochondrial dysfunction and acute fatty liver of pregnancy","volume":"23","author":"Ramanathan","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2025100323020955500_ref7","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.2147\/JIR.S275595","article-title":"Reactive oxygen species: drivers of physiological and pathological processes","volume":"13","author":"Checa","year":"2020","journal-title":"J Inflamm Res"},{"key":"2025100323020955500_ref8","doi-asserted-by":"publisher","first-page":"111326","DOI":"10.1016\/j.biopha.2021.111326","article-title":"New insight and potential therapy for NAFLD: CYP2E1 and flavonoids","volume":"137","author":"Wang","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"2025100323020955500_ref9","doi-asserted-by":"publisher","first-page":"108918","DOI":"10.1016\/j.cbi.2019.108918","article-title":"The role of cytochrome P4502E1 in the pathogenesis of alcoholic liver disease and carcinogenesis","volume":"316","author":"Seitz","year":"2020","journal-title":"Chem Biol Interact"},{"key":"2025100323020955500_ref10","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.3390\/ijms22052350","article-title":"Treatments for NAFLD: state of art","volume":"22","author":"Mantovani","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2025100323020955500_ref11","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3389\/fphar.2020.00351","article-title":"The impacts of herbal medicines and natural products on regulating the hepatic lipid metabolism","volume":"11","author":"Li","year":"2020","journal-title":"Front Pharmacol"},{"key":"2025100323020955500_ref12","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/molecules28010272","article-title":"Terpenoids: natural compounds for non-alcoholic fatty liver disease (NAFLD) therapy","volume":"28","author":"Yao","year":"2022","journal-title":"Molecules"},{"key":"2025100323020955500_ref13","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.sajb.2010.05.008","article-title":"Geraniol\u2014a review of a commercially important fragrance material","volume":"76","author":"Chen","year":"2010","journal-title":"S Afr J Bot"},{"key":"2025100323020955500_ref14","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/jgh.13272","article-title":"Treatment with geraniol ameliorates methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in rats","volume":"31","author":"Chen","year":"2016","journal-title":"J Gastroenterol Hepatol"},{"key":"2025100323020955500_ref15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1055\/a-0750-6907","article-title":"Pharmacological properties of geraniol\u2014a review","volume":"85","author":"Lei","year":"2019","journal-title":"Planta Med"},{"key":"2025100323020955500_ref16","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.2147\/JIR.S354878","article-title":"Reduction of hepatic steatosis, oxidative stress, inflammation, ballooning and insulin resistance after therapy with safranal in NAFLD animal model: a new approach","volume":"15","author":"Sabir","year":"2022","journal-title":"J Inflamm Res"},{"key":"2025100323020955500_ref17","doi-asserted-by":"publisher","first-page":"559","DOI":"10.3109\/15376516.2015.1070225","article-title":"Geraniol attenuates 2-acetylaminofluorene induced oxidative stress, inflammation and apoptosis in the liver of wistar rats","volume":"25","author":"Hasan","year":"2015","journal-title":"Toxicol Mech Methods"},{"key":"2025100323020955500_ref18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12906-021-03396-x","article-title":"Administration of hydro-alcoholic extract of spinach improves oxidative stress and inflammation in high-fat diet-induced NAFLD rats","volume":"21","author":"Amirinejad","year":"2021","journal-title":"BMC Complement Med Ther"},{"key":"2025100323020955500_ref19","doi-asserted-by":"publisher","first-page":"109199","DOI":"10.1016\/j.cbi.2020.109199","article-title":"High fat diet-triggered non-alcoholic fatty liver disease: a review of proposed mechanisms","volume":"330","author":"Lian","year":"2020","journal-title":"Chem Biol Interact"},{"key":"2025100323020955500_ref20","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00018-018-2947-0","article-title":"Molecular pathways of nonalcoholic fatty liver disease development and progression","volume":"76","author":"Bessone","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"2025100323020955500_ref21","doi-asserted-by":"publisher","first-page":"15489","DOI":"10.3390\/ijms232415489","article-title":"Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment","volume":"23","author":"Guo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2025100323020955500_ref22","doi-asserted-by":"publisher","first-page":"1149239","DOI":"10.3389\/fendo.2023.1149239","article-title":"The crucial role and mechanism of insulin resistance in metabolic disease","volume":"14","author":"Zhao","year":"2023","journal-title":"Front Endocrinol"},{"key":"2025100323020955500_ref23","doi-asserted-by":"publisher","first-page":"3999","DOI":"10.3748\/wjg.v29.i25.3999","article-title":"Insulin resistance and adipose tissue interactions as the cornerstone of metabolic (dysfunction)-associated fatty liver disease pathogenesis","volume":"29","author":"Pal","year":"2023","journal-title":"World J Gastroenterol"},{"key":"2025100323020955500_ref24","doi-asserted-by":"publisher","DOI":"10.24294\/as.v1i3.903","article-title":"Chemical induced liver injury: types, mechanisms and biomarkers","volume":"1","author":"Sachan","year":"2023","journal-title":"Anat Sci"},{"key":"2025100323020955500_ref25","doi-asserted-by":"publisher","first-page":"e34200","DOI":"10.1371\/journal.pone.0034200","article-title":"Natural terpenes prevent mitochondrial dysfunction, oxidative stress and release of apoptotic proteins during nimesulide-hepatotoxicity in rats","volume":"7","author":"Singh","year":"2012","journal-title":"PLoS One"},{"key":"2025100323020955500_ref26","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1042\/BCJ20210071","article-title":"SREBP-1c and lipogenesis in the liver: an update","volume":"478","author":"Ferr\u00e9","year":"2021","journal-title":"Biochem J"},{"key":"2025100323020955500_ref27","doi-asserted-by":"publisher","first-page":"e2133","DOI":"10.1002\/biof.2133","article-title":"Delphinidin or \u03b1-amyrin attenuated liver steatosis and metabolic disarrangement in rats fed a high-fat diet","volume":"51","author":"Ali","year":"2025","journal-title":"BioFactors"},{"key":"2025100323020955500_ref28","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3390\/antiox10020174","article-title":"Role of oxidative stress in the pathogenesis of non-alcoholic fatty liver disease: implications for prevention and therapy","volume":"10","author":"Arroyave-Ospina","year":"2021","journal-title":"Antioxidants"},{"key":"2025100323020955500_ref29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/livers2010003","article-title":"Oxidative stress in non-alcoholic fatty liver disease","volume":"2","author":"Smirne","year":"2022","journal-title":"Livers"},{"key":"2025100323020955500_ref30","doi-asserted-by":"publisher","first-page":"fcad356","DOI":"10.1093\/braincomms\/fcad356","article-title":"Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants","volume":"6","author":"Houldsworth","year":"2024","journal-title":"Brain Commun"},{"key":"2025100323020955500_ref31","doi-asserted-by":"publisher","first-page":"9566","DOI":"10.1038\/s41598-025-93120-3","article-title":"Gallic and glycyrrhetinic acids prevent azithromycin-induced liver damage in rats by mitigating oxidative stress and inflammation","volume":"15","author":"Ali","year":"2025","journal-title":"Sci Rep"},{"key":"2025100323020955500_ref32","doi-asserted-by":"publisher","first-page":"1353029","DOI":"10.3389\/fphar.2024.1353029","article-title":"Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1\/Nrf2\/NF-\u03baB\/TNF-\u03b1 signaling pathways","volume":"15","author":"Botros","year":"2024","journal-title":"Front Pharmacol"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/77\/10\/1439\/64068096\/rgaf053.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/77\/10\/1439\/64068096\/rgaf053.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T03:02:15Z","timestamp":1759546935000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/77\/10\/1439\/8236511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,16]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,8,16]]},"published-print":{"date-parts":[[2025,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgaf053","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,8,16]]}}}