{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:12:47Z","timestamp":1791317567606,"version":"4.3.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T00:00:00Z","timestamp":1722643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Selcuk University Scientific Research Projects","award":["22401119"],"award-info":[{"award-number":["22401119"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The aim of this study was to determine the single and combined antidiabetic activity and side effects of the retinoid X receptor agonist bexarotene and the thioredoxin-interacting protein inhibitor and peroxisome proliferator-activated receptor \u03b3 and AMP-activated protein kinase activator icariin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The rats were grouped as healthy (control), diabetes, diabetes + bexarotene (20 mg\/kg), diabetes + icariin (60 mg\/kg), diabetes + bexarotene (10 mg\/kg) + icariin (30 mg\/kg) low-dose combination and diabetes + bexarotene (20 mg\/kg) + icariin (60 mg\/kg) high-dose combination groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Icariin treatment led to a significant reduction in glucose levels compared with the diabetes control group, a remarkable outcome observed 45 days after the initial application. HbA1c levels of the icariin and low-dose combination treatment groups were significantly lower than in the diabetes group. Notably, icariin treatment also significantly elevated HOMA-\u03b2 levels, which is indicative of improved \u03b2-cell function. Icariin significantly decreased glucose levels at 30 and 120 min in the oral glucose tolerance test. Moreover, it ameliorated hepatocyte degeneration, hepatic cord dissociation, congestion, mononuclear cell infiltration in the liver, and degeneration in the pancreas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Icariin treatment exhibited robust antidiabetic effects with fewer side effects than other treatment options in this study. In future studies, long-term and varying doses of icariin will contribute to the development of novel antidiabetic drugs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgae100","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T19:30:38Z","timestamp":1721331038000},"page":"1474-1481","source":"Crossref","is-referenced-by-count":7,"title":["Exploring the combined therapeutic efficacy of bexarotene and icariin in type 2 diabetic rats"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2738-6911","authenticated-orcid":false,"given":"Burak","family":"Dik","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Selcuk University , Konya, 42130 ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-0336","authenticated-orcid":false,"given":"Tugba Melike","family":"Parlak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Selcuk University , Konya, 42130 ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Burak","family":"Ates","sequence":"additional","affiliation":[{"name":"Department of Pathology, Selcuk University , Konya, 42130 ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-0793","authenticated-orcid":false,"given":"Oznur","family":"Tufan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Selcuk University , Konya, 42130 ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,3]]},"reference":[{"key":"2024110408190141100_CIT0001","first-page":"107","article-title":"Epidemiology of type 2 diabetes\u2013global burden of disease and forecasted trends","volume":"1","author":"Khan","year":"2020","journal-title":"J Epidemiol Glob Health"},{"key":"2024110408190141100_CIT0002","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","article-title":"Type 2 diabetes","volume":"389","author":"Chatterjee","year":"2017","journal-title":"Lancet"},{"key":"2024110408190141100_CIT0003","first-page":"19","article-title":"Insulin and insulin resistance","volume":"2","author":"Wilcox","year":"2005","journal-title":"Clin Biochem Rev"},{"key":"2024110408190141100_CIT0004","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1139\/cjpp-2017-0769","article-title":"Combined treatment with interleukin-1 and tumor necrosis factor-alpha antagonists improve type 2 diabetes in rats","volume":"96","author":"Dik","year":"2018","journal-title":"Can J Physiol Pharmacol"},{"key":"2024110408190141100_CIT0005","doi-asserted-by":"crossref","first-page":"15019","DOI":"10.1038\/nrdp.2015.19","article-title":"Type 2 diabetes mellitus","volume":"1","author":"Defronzo","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"2024110408190141100_CIT0006","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/fcp.12975","article-title":"The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats","volume":"38","author":"Korkmaz","year":"2024","journal-title":"Fundam Clin Pharm"},{"key":"2024110408190141100_CIT0007","first-page":"69","article-title":"The treatment of type 2 diabetes","volume":"5","author":"Pfeiffer","year":"2014","journal-title":"Dtsch Arztebl Int"},{"key":"2024110408190141100_CIT0008","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1124\/pr.110.003319","article-title":"Novel pharmacological approaches to the treatment of type 2 diabetes","volume":"64","author":"Verspohl","year":"2012","journal-title":"Pharmacol Rev"},{"key":"2024110408190141100_CIT0009","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/DMSO.S232221","article-title":"Thioredoxin-interacting protein as a novel potential therapeutic target in diabetes mellitus and its underlying complications","volume":"13","author":"Wondafrash","year":"2020","journal-title":"Diabetes Metab Syndr Obes"},{"key":"2024110408190141100_CIT0010","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1096\/fj.08-111690","article-title":"Thioredoxin-interacting protein deficiency induces Akt\/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes","volume":"22","author":"Chen","year":"2008","journal-title":"FASEB J"},{"key":"2024110408190141100_CIT0011","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.3906\/sag-2004-38","article-title":"Potential antidiabetic activity of benzimidazole derivative albendazole and lansoprazoledrugs in different doses in experimental type 2 diabetic rats","volume":"51","author":"Dik","year":"2021","journal-title":"Turk J Med Sci"},{"key":"2024110408190141100_CIT0012","doi-asserted-by":"crossref","first-page":"187","DOI":"10.5507\/bp.2007.033","article-title":"Retinoids, rexinoids and their cognate nuclear receptors: character and their role in chemoprevention of selected malignant diseases","volume":"151","author":"Brtko","year":"2007","journal-title":"Biomed Pap Med Fac Palacky Univ Olomouc"},{"key":"2024110408190141100_CIT0013","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1210\/en.2003-0907","article-title":"Activation of the retinoid X receptor suppresses appetite in the rat","volume":"145","author":"Ogilvie","year":"2004","journal-title":"Endocrinology"},{"key":"2024110408190141100_CIT0014","doi-asserted-by":"crossref","first-page":"94156","DOI":"10.1155\/2007\/94156","article-title":"Therapeutic potential of retinoid x receptor modulators for the treatment of the metabolic syndrome","volume":"2007","author":"Pinaire","year":"2007","journal-title":"PPAR Research"},{"key":"2024110408190141100_CIT0015","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/bs.apha.2021.01.004","article-title":"Potential therapeutic uses of rexinoids","volume":"91","author":"Leal","year":"2021","journal-title":"Adv Pharmacol"},{"key":"2024110408190141100_CIT0016","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1089\/rej.2013.1497","article-title":"New hope from an old drug: fighting Alzheimer\u2019s disease with the cancer drug bexarotene (targretin)","volume":"16","author":"Aicardi","year":"2013","journal-title":"Rejuvenation Res"},{"key":"2024110408190141100_CIT0017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12032-021-01476-z","article-title":"Bexarotene inhibits cell proliferation by inducing oxidative stress, DNA damage and apoptosis via PPAR\u03b3\/NF-\u03baB signaling pathway in C6 glioma cells","volume":"38","author":"Hacioglu","year":"2021","journal-title":"Med Oncol"},{"key":"2024110408190141100_CIT0018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-018-4224-x","article-title":"Bexarotene inhibits the viability of non-small cell lung cancer cells via slc10a2\/PPAR\u03b3\/PTEN\/mTOR signaling pathway","volume":"18","author":"Ai","year":"2018","journal-title":"BMC cancer"},{"key":"2024110408190141100_CIT0019","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/386407a0","article-title":"Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists","volume":"6623","author":"Mukherjee","year":"1997","journal-title":"Nature"},{"key":"2024110408190141100_CIT0020","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1124\/mol.59.2.170","article-title":"Metabolic effects of rexinoids: tissue-specific regulation of lipoprotein lipase activity","volume":"2","author":"Davies","year":"2001","journal-title":"Mol Pharmacol"},{"key":"2024110408190141100_CIT0021","doi-asserted-by":"crossref","first-page":"38317","DOI":"10.1074\/jbc.M505853200","article-title":"Distinct mechanisms of glucose lowering by specific agonists for peroxisomal proliferator activated receptor \u03b3 and retinoic acid X receptors","volume":"280","author":"Li","year":"2005","journal-title":"J Biol Chem"},{"key":"2024110408190141100_CIT0022","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1177\/106002800103500903","article-title":"Oral bexarotene in the treatment of cutaneous T-cell lymphoma","volume":"35","author":"Wong","year":"2001","journal-title":"Ann Pharmacother"},{"key":"2024110408190141100_CIT0023","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.3390\/ijms22052754","article-title":"Role of thioredoxin-interacting protein in diseases and its therapeutic outlook","volume":"22","author":"Qayyum","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2024110408190141100_CIT0024","first-page":"1095","article-title":"TXNIP in metabolic regulation: physiological role and therapeutic outlook","volume":"9","author":"Mohammad Alhawiti","year":"2017","journal-title":"Curr Drug Targets"},{"key":"2024110408190141100_CIT0025","doi-asserted-by":"crossref","first-page":"e158","DOI":"10.1371\/journal.pmed.0040158","article-title":"TXNIP regulates peripheral glucose metabolism in humans","volume":"4","author":"Parikh","year":"2007","journal-title":"PLoS Med"},{"key":"2024110408190141100_CIT0026","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcjd.2018.02.012","article-title":"Serum vitamin D and its upregulated protein, thioredoxin interacting protein, are associated with beta-cell dysfunction in adult patients with type 1 and type 2 diabetes","volume":"42","author":"Omar","year":"2018","journal-title":"Can J Diabetes"},{"key":"2024110408190141100_CIT0027","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1210\/en.2008-0646","article-title":"Thioredoxin binding protein-2\/thioredoxin-interacting protein is a critical regulator of insulin secretion and peroxisome proliferator-activated receptor function","volume":"3","author":"Oka","year":"2009","journal-title":"Endocrinology"},{"key":"2024110408190141100_CIT0028","first-page":"2690","article-title":"Icariin treatment reduces blood glucose levels in type 2 diabetic rats and protects pancreatic function","volume":"4","author":"Li","year":"2020","journal-title":"Exp Ther Med"},{"key":"2024110408190141100_CIT0029","doi-asserted-by":"crossref","first-page":"848","DOI":"10.2337\/db11-0955","article-title":"Preventing \u03b2-cell loss and diabetes with calcium channel blockers","volume":"61","author":"Xu","year":"2012","journal-title":"Diabetes"},{"key":"2024110408190141100_CIT0030","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1111\/bph.12226","article-title":"Quercetin and allopurinol reduce liver thioredoxin-interacting protein to alleviate inflammation and lipid accumulation in diabetic rats","volume":"169","author":"Wang","year":"2013","journal-title":"Br J Pharmacol"},{"key":"2024110408190141100_CIT0031","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1111\/j.1743-6109.2011.02421.x","article-title":"Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats","volume":"8","author":"Liu","year":"2011","journal-title":"J Sex Med"},{"key":"2024110408190141100_CIT0032","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/mnfr.201300409","article-title":"Plant polyphenols in the treatment of age-associated diseases: revealing the pleiotropic effects of icariin by network analysis","volume":"58","author":"Schluesener","year":"2014","journal-title":"Mol Nutr Food Res"},{"key":"2024110408190141100_CIT0033","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.lfs.2015.01.006","article-title":"Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii","volume":"126","author":"Li","year":"2015","journal-title":"Life Sci"},{"key":"2024110408190141100_CIT0034","doi-asserted-by":"crossref","first-page":"734","DOI":"10.3389\/fphar.2017.00734","article-title":"Icariin, an anti-atherosclerotic drug from Chinese medicinal herb horny goat weed","volume":"8","author":"Fang","year":"2017","journal-title":"Front Pharmacol"},{"key":"2024110408190141100_CIT0035","doi-asserted-by":"crossref","first-page":"110675","DOI":"10.1016\/j.biopha.2020.110675","article-title":"Icariin and its metabolites regulate lipid metabolism: from effects to molecular mechanisms","volume":"131","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother"},{"key":"2024110408190141100_CIT0036","doi-asserted-by":"crossref","first-page":"108930","DOI":"10.1016\/j.biopha.2019.108930","article-title":"Icariin induces irisin\/FNDC5 expression in C2C12 cells via the AMPK pathway","volume":"115","author":"Chen","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"2024110408190141100_CIT0037","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.3389\/fphar.2018.01180","article-title":"Icariin ameliorates palmitate-induced insulin resistance through reducing thioredoxin-interacting protein (TXNIP) and suppressing ER stress in C2C12 myotubes","volume":"9","author":"Li","year":"2018","journal-title":"Front Pharmacol"},{"key":"2024110408190141100_CIT0038","first-page":"671","article-title":"Epimedium koreanum Nakai and its main constituent icariin suppress lipid accumulation during adipocyte differentiation of 3T3-L1 preadipocytes","volume":"9","author":"Yunk-Yung","year":"2016","journal-title":"Chin J Nat Med"},{"key":"2024110408190141100_CIT0039","first-page":"4099","article-title":"Effects of icariside II ameliorates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by activating Akt\/NOS\/NF-\u03baB signaling","volume":"3","author":"Yang","year":"2018","journal-title":"Mol Med Rep"},{"key":"2024110408190141100_CIT0040","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.mce.2018.01.014","article-title":"Icariin modulates mitochondrial function and apoptosis in high glucose-induced glomerular podocytes through G protein-coupled estrogen receptors","volume":"473","author":"Qiao","year":"2018","journal-title":"Mol Cell Endocrinol"},{"key":"2024110408190141100_CIT0041","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jep.2011.10.015","article-title":"Protective effect of Icariin on the early stage of experimental diabetic nephropathy induced by streptozotocin via modulating transforming growth factor \u03b21 and type IV collagen expression in rats","volume":"3","author":"Qi","year":"2011","journal-title":"J Ethnopharmacol"},{"key":"2024110408190141100_CIT0042","doi-asserted-by":"crossref","first-page":"866","DOI":"10.3390\/ijms13010866","article-title":"Icariin ameliorates streptozotocin-induced diabetic retinopathy in vitro and in vivo","volume":"13","author":"Xin","year":"2012","journal-title":"Int J Mol Sci"},{"key":"2024110408190141100_CIT0043","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1159\/000505408","article-title":"Icariin attenuates diabetic cardiomyopathy and downregulates extracellular matrix proteins in heart tissue of type 2 diabetic rats","volume":"105","author":"Qiao","year":"2020","journal-title":"Pharmacology"},{"key":"2024110408190141100_CIT0044","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1039\/D0FO02335C","article-title":"Icariin ameliorates streptozocin-induced diabetic nephropathy through suppressing the TLR4\/NF-\u03baB signal pathway","volume":"3","author":"Qi","year":"2021","journal-title":"Food Funct"},{"key":"2024110408190141100_CIT0045","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.phrs.2005.05.004","article-title":"Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening","volume":"52","author":"Srinivasan","year":"2005","journal-title":"Pharmacol Res"},{"key":"2024110408190141100_CIT0046","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2147\/JEP.S233111","article-title":"Alpha-mangostin improves cardiac hypertrophy and fibrosis and associated biochemical parameters in high-fat\/high-glucose diet and low-dose streptozotocin injection-induced type 2 diabetic rats","volume":"12","author":"Soetikno","year":"2020","journal-title":"J Exp Pharmacol"},{"key":"2024110408190141100_CIT0047","volume-title":"Manual of histologic staining methods of the Armed Forces Institute of Pathology","author":"Luna","year":"1968"},{"key":"2024110408190141100_CIT0048","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2754\/avb202190040421","article-title":"The effect of etanercept and anakinra on experimental type 2 diabetes pathology in rats","volume":"90","author":"Ozdemir","year":"2021","journal-title":"Acta Vet Brno"},{"key":"2024110408190141100_CIT0049","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1055\/a-0837-0975","article-title":"Icariin attenuates high glucose-induced apoptosis, oxidative stress, and inflammation in human umbilical venous endothelial cells","volume":"85","author":"Sun","year":"2019","journal-title":"Planta Med"},{"key":"2024110408190141100_CIT0050","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejphar.2015.03.059","article-title":"Effects of Icariin on insulin resistance via the activation of AMPK pathway in C2C12 mouse muscle cells","volume":"758","author":"Han","year":"2015","journal-title":"Eur J Pharmacol"},{"key":"2024110408190141100_CIT0051","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/cbf.907","article-title":"Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cells","volume":"19","author":"Blumentrath","year":"2001","journal-title":"Cell Biochem Funct"},{"key":"2024110408190141100_CIT0052","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/S0026-0495(97)90009-3","article-title":"Retinoid-X receptors and the effects of 9-cis-retinoic acid on insulin secretion from RINm5F cells","volume":"46","author":"Chertow","year":"1997","journal-title":"Metabolism"},{"key":"2024110408190141100_CIT0053","doi-asserted-by":"crossref","first-page":"e20467","DOI":"10.1371\/journal.pone.0020467","article-title":"Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXR\u03b3 in skeletal muscle","volume":"6","author":"Sugita","year":"2011","journal-title":"PLoS One"},{"key":"2024110408190141100_CIT0054","doi-asserted-by":"crossref","first-page":"19721","DOI":"10.1074\/jbc.M311729200","article-title":"Effects of rexinoids on glucose transport and insulin-mediated signaling in skeletal muscles of diabetic (db\/db) mice","volume":"279","author":"Shen","year":"2004","journal-title":"J Biol Chem"},{"key":"2024110408190141100_CIT0055","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.yjmcc.2013.01.017","article-title":"Activation of retinoid receptor-mediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats","volume":"57","author":"Guleria","year":"2013","journal-title":"J Mol Cell Cardiol"},{"key":"2024110408190141100_CIT0056","doi-asserted-by":"crossref","first-page":"469","DOI":"10.4149\/neo_2012_060","article-title":"Melatonin enhanced bexarotene efficacy in experimental mammary carcinogenesis","volume":"59","author":"Orendas","year":"2012","journal-title":"Neoplasma"},{"key":"2024110408190141100_CIT0057","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1210\/jc.2006-2822","article-title":"Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones","volume":"7","author":"Smit","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2024110408190141100_CIT0058","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1128\/MCB.19.5.3372","article-title":"Retinoid X receptor (RXR) agonist-induced activation of dominant-negative RXR-retinoic acid receptor \u03b1403 heterodimers is developmentally regulated during myeloid differentiation","volume":"5","author":"Johnson","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2024110408190141100_CIT0059","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.bjp.0705113","article-title":"RXR activators molecular signalling: involvement of a PPAR\u03b1-dependent pathway in the liver and kidney, evidence for an alternative pathway in the heart","volume":"138","author":"Ouamrane","year":"2003","journal-title":"Br J Pharmacol"},{"key":"2024110408190141100_CIT0060","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/bdd.2337","article-title":"In vitro\u2013in vivo extrapolation of bexarotene metabolism in the presence of chronic kidney disease and acute kidney injury in rat using physiologically based pharmacokinetic modeling and extrapolation to human","volume":"3","author":"Alsmadi","year":"2023","journal-title":"Biopharm Drug Dispos"},{"key":"2024110408190141100_CIT0061","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3390\/molecules22060986","article-title":"Potential of icariin metabolites from Epimedium koreanum Nakai as antidiabetic therapeutic agents","volume":"22","author":"Kim","year":"2017","journal-title":"Molecules"},{"key":"2024110408190141100_CIT0062","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2165\/00128071-200001040-00006","article-title":"Bexarotene","volume":"1","author":"Lowe","year":"2000","journal-title":"Am J Clin Dermatol"},{"key":"2024110408190141100_CIT0063","doi-asserted-by":"crossref","first-page":"21274","DOI":"10.3390\/molecules201219763","article-title":"Comparative pharmacokinetics study of icariin and icariside II in rats","volume":"20","author":"Cheng","year":"2015","journal-title":"Molecules"},{"key":"2024110408190141100_CIT0064","first-page":"301","article-title":"Effects of icaritin on cytochrome P450 enzymes in rats","volume":"4","author":"Liang","year":"2014","journal-title":"Pharmazie"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/76\/11\/1474\/60213066\/rgae100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/76\/11\/1474\/60213066\/rgae100.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T08:19:46Z","timestamp":1730708386000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/76\/11\/1474\/7716648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,3]]},"references-count":64,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,8,3]]},"published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgae100","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11]]},"published":{"date-parts":[[2024,8,3]]}}}