{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:12:55Z","timestamp":1783476775340,"version":"3.55.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"am","delay-in-days":357,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/501100011665","name":"Deanship of Scientific Research, King Saud University","doi-asserted-by":"publisher","award":["RG-1440-033"],"award-info":[{"award-number":["RG-1440-033"]}],"id":[{"id":"10.13039\/501100011665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011665","name":"Deanship of Scientific Research, King Saud University","doi-asserted-by":"crossref","award":["RG-1440-033"],"award-info":[{"award-number":["RG-1440-033"]}],"id":[{"id":"10.13039\/501100011665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Raspberry Ketone (RK) is a natural phenolic compound which is marketed nowadays as a popular weight-reducing remedy, with reported antioxidant and anti-inflammatory activities. However, its biological activity is not fully elucidated. Hepatotoxicity is the leading cause of acute liver failure in Europe and North America, and its management is still challenging. Therefore, this study aimed to assess the therapeutic detoxification activity of RK against liver injury in vivo and to explore the underlying mechanisms using carbon tetrachloride (CCl4)-induced hepatotoxicity as a model. First, a dose\u2013response study using 4 different doses, 25, 50, 100, and 200 mg kg\u22121 day\u22121, of RK was conducted. RK was administered for 5 days as a pretreatment, followed by a single dose of CCl4 (1 ml kg\u22121, 1\u2009:\u20091 v\/v CCl4\u2009:\u2009olive oil). The RK dose of 200 mg kg\u22121 showed the greatest protective effect and was selected for further investigations. CCl4 hepatotoxicity was confirmed by elevation of liver enzymes, and histopathological examination. CCl4-induced oxidative stress was evident from increased lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) along with depleted superoxide dismutase (SOD), reduced glutathione (GSH), and total antioxidant capacity (TAC). Increased oxidative stress was associated with increased cytochrome c expression with subsequent activation of caspase-9 and caspase-3, in addition to DNA fragmentation reflecting apoptosis. CCl4 also induced the expression of inflammatory cytokines (NF-\u03baB and TNF-\u03b1). Interestingly, RK hepatoprotective activity was evident from the reduction of liver enzymes, and maintenance of hepatocyte integrity and microstructures as evaluated by histopathological examination using H and E, and transmission electron microscopy. The antioxidant activity of RK was demonstrated by the increase of TAC, SOD, and GSH, with a concomitant decrease of the TBARS level. Moreover, RK pretreatment inhibited CCl4-induced upregulation of inflammatory mediators. RK antiapoptotic activity was indicated by the reduction of the expression of cytoplasmic cytochrome-C, a decrease of caspases, and inhibition of DNA fragmentation. In conclusion, this study demonstrates that RK is a promising hepatoprotective agent. The underlying mechanisms include antioxidant, anti-inflammatory, and anti-apoptotic activities. This is the first study reporting RK hepatoprotective activity in acute hepatic injury and approves its antiapoptotic effect in the liver.<\/jats:p>","DOI":"10.1039\/c9tx00068b","type":"journal-article","created":{"date-parts":[[2019,6,30]],"date-time":"2019-06-30T22:04:14Z","timestamp":1561932254000},"page":"663-676","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Hepatoprotective activity of raspberry ketone is mediated via inhibition of the NF-\u03baB\/TNF-\u03b1\/caspase axis and mitochondrial apoptosis in chemically induced acute liver injury"],"prefix":"10.1093","volume":"8","author":[{"given":"Dalia","family":"Fouad","sequence":"first","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia"},{"name":"Department of Zoology and Entomology, Faculty of Science, Helwan University, Ein Helwan, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-868X","authenticated-orcid":false,"given":"Amira","family":"Badr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia Tel: +96659575917"},{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Ain Shams University, Heliopolis, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala A.","family":"Attia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia Tel: +96659575917"},{"name":"Department of Biochemistry, College of Pharmacy, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"issue":"Suppl. 1","key":"2020012303581192700_cit1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/liv.13643","volume":"38","author":"Ara\u00fajo","year":"2018","journal-title":"Liver Int."},{"issue":"2","key":"2020012303581192700_cit2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1055\/s-0035-1550054","volume":"35","author":"Bataller","year":"2015","journal-title":"Semin. Liver Dis."},{"issue":"4","key":"2020012303581192700_cit3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.4103\/0975-1483.104366","volume":"4","author":"Mahmud","year":"2012","journal-title":"J. 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