{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:10:56Z","timestamp":1791544256800,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Raspberry Ketone (RK) and Resveratrol (RSV) are natural phenolic antioxidants and anti\u2010inflammatory agents. However, its combined pharmacokinetic and pharmacodynamics potentials are not reported. The study aims to assess the combined effect of RK with RSV to protect rats from carbon\u2010tetrachloride (CCl4) induced oxidative stress and NASH. The toxicant CCl4 was employed at a concentration of 1\u2009mL\/kg as a 1:1 (v\/v) mixture with olive oil twice weekly for 6 weeks to induce liver toxicity. Animal treatment was followed for 2 weeks. Silymarin was used as a standard control drug to compare the hepatoprotective effect of RK and RSV. Hepatic histology, oxidative stress, MMP, reduced glutathione (GSH), plasma levels of SGOT, SGPT, and lipid profile (total cholesterol and triglycerides) were measured. Anti\u2010inflammation genes (IL\u201010), and fibrotic genes (TGF\u2010\u03b2) were also examined in liver tissue. Oral administration of combined RK with RSV (50\u2009+\u200950\u2009mg\/kg for 2 weeks) showed significantly more hepatoprotection by significantly decreasing elevated plasma markers and lipid profile than alone RK and RSV (100\u2009mg\/kg daily for 2 weeks). It also significantly alleviated the hepatic lipid peroxidation, restoring the activities of GSH levels in the liver. RT\u2010PCR and Immunoblotting studies confirmed that significantly upregulation of anti\u2010inflammation genes and protein expression (MMP\u20109) ameliorated the disease. Pharmacokinetic studies confirmed more synergistic stability in simulated gastric\u2010intestinal fluids (FaSSGF, FaSSIF) and rat liver microsomes (CYP\u2010450, NADPH oxidation &amp; glucuronidation. Moreover, coadministration of drugs augmented the relative bioavailability, V<jats:sub>d\/<\/jats:sub>F (L\/Kg), and MRT<jats:sub>0\u2010\u221e(<\/jats:sub>h), which leads to more efficacy. This pharmacokinetic and pharmacodynamic reveals a new adjuvant therapy for the treatment of steatohepatitis.<\/jats:p>","DOI":"10.1002\/jbt.23336","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T08:40:09Z","timestamp":1680511209000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The combined effect of Raspberry Ketone with Resveratrol against oxidative stress and steatohepatitis in rats: Pharmacokinetic and pharmacodynamic studies"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8790-4704","authenticated-orcid":false,"given":"Saurabh","family":"Verma","sequence":"first","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacokinetics CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh K.","family":"Goand","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacokinetics CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivam","family":"Rathaur","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacokinetics CSIR\u2010Central Drug Research Institute Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacokinetics CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Katekar","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacokinetics CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7703-9307","authenticated-orcid":false,"given":"Jiaur R.","family":"Gayen","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacokinetics CSIR\u2010Central Drug Research Institute Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"},{"name":"Division of Pharmacology CSIR\u2010Central Drug Research Institute Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13643"},{"key":"e_1_2_10_3_1","first-page":"146","volume-title":"Liver fibrosis in alcoholic liver disease","author":"Bataller R.","year":"2015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/0975-1483.104366"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161226126"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20022445"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.02.059"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.10.034"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2020.1772279"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2011.1717"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9tx00068b"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.11.079"},{"issue":"4","key":"e_1_2_10_13_1","first-page":"111","volume":"60","author":"Spanier G.","year":"2009","journal-title":"J.\u00a0Physiol.\u00a0Pharmacol"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfda.2018.01.006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/fft2.129"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2018.1489852"},{"key":"e_1_2_10_17_1","first-page":"5","volume":"7","author":"Ismail R. 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