{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T18:26:38Z","timestamp":1772562398524,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate the therapeutic role of calorie-restricted diet (CR) and raspberry ketone (RK) in non-alcoholic fatty liver disease (NAFLD) and the implication of sphingosine kinase-1 (SphK1)\/sphingosine-1-phosphate (S1P) and toll-like receptor 4 (TLR4) signalling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>NAFLD was induced by feeding rats high-fat-fructose-diet (HFFD) for 6 weeks. Rats were then randomly assigned to three groups (n = 6 each); NAFLD group continued on HFFD for another 8 weeks. CR group was switched to CR diet (25% calorie restriction) for 8 weeks and RK group was switched to normal diet and received RK (55 mg\/kg\/day; orally) for 8 weeks. Another six rats were used as normal control.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>HFFD induced a state of NAFLD indicated by increased fat deposition in liver tissue along with dyslipidemia, elevated liver enzymes, oxidative stress and inflammation. Either CR diet or RK reversed these changes and decreased HFFD-induced elevation of hepatic SphK1, S1P, S1PR1 and TLR4. Of notice, RK along with a normal calorie diet was even better than CR alone in most studied parameters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>SphK1\/S1P and TLR4 are interconnected and related to the establishment of HFFD-induced NAFLD and can be modulated by RK. Supplementation of RK without calorie restriction to patients with NAFLD unable to follow CR diet to achieve their treatment goals would be a promising therapeutic modality.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgad044","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T18:57:01Z","timestamp":1683831421000},"page":"985-994","source":"Crossref","is-referenced-by-count":2,"title":["Raspberry ketone improves non-alcoholic fatty liver disease induced in rats by modulating sphingosine kinase\/sphingosine-1-phosphate and toll-like receptor 4 pathways"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1729-0898","authenticated-orcid":false,"given":"Kareem M","family":"Abdelraheem","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Sinai University \u2013 Qantara Branch , Ismailia ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahla N","family":"Younis","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Zagazig University , Zagazig ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Human Medicine, Zagazig University , Zagazig ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar E","family":"Elswefy","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Zagazig University , Zagazig ,","place":["Egypt"]},{"name":"Biochemistry Department, Faculty of Pharmacy, Delta University for Sciences and Technology , Gamasa ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sousou I","family":"Ali","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Zagazig University , Zagazig ,","place":["Egypt"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,7,1]]},"reference":[{"key":"2024103012241260800_CIT0001","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/med.21515","article-title":"Progress and challenges in the prevention and control of nonalcoholic fatty liver disease","volume":"39","author":"Cai","year":"2019","journal-title":"Med Res Rev"},{"key":"2024103012241260800_CIT0002","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/hep.22603","article-title":"Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management","volume":"49","author":"Vuppalanchi","year":"2009","journal-title":"Hepatology"},{"key":"2024103012241260800_CIT0003","first-page":"205","article-title":"Is visceral fat reduction necessary to favour metabolic changes in the liver?","volume":"21","author":"Finelli","year":"2012","journal-title":"J Gastrointestin Liver Dis"},{"key":"2024103012241260800_CIT0004","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.3748\/wjg.v17.i29.3377","article-title":"Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence","volume":"17","author":"Zelber-Sagi","year":"2011","journal-title":"World J Gastroenterol"},{"key":"2024103012241260800_CIT0005","doi-asserted-by":"crossref","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"2024103012241260800_CIT0006","doi-asserted-by":"crossref","first-page":"154925","DOI":"10.1016\/j.metabol.2021.154925","article-title":"Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease","volume":"126","author":"Negi","year":"2022","journal-title":"Metabolism"},{"key":"2024103012241260800_CIT0007","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222413424","article-title":"It is high time physicians thought of natural products for alleviating NAFLD. 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