{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:53Z","timestamp":1786978193962,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["ES1617Y5030"],"award-info":[{"award-number":["ES1617Y5030"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Mass Spectrom"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Phlorizin (PRZ) is a natural product that belongs to a class of dihydrochalcones. The unique pharmacological property of PRZ is to block glucose absorption or reabsorption through specific and competitive inhibitors of the sodium\/glucose cotransporters (SGLTs) in the intestine (SGLT1) and kidney (SGLT2). This results in glycosuria by inhibiting renal reabsorption of glucose and can be used as an adjuvant treatment for type 2 diabetes. The pharmacokinetic profile, metabolites of the PRZ, and efficacy of metabolites towards SGLTs are unknown. Therefore, the present study on the characterization of hitherto unknown in vivo metabolites of PRZ and pharmacokinetic profiling using liquid chromatography\u2010electrospray ionization tandem mass spectrometry (LC\/ESI\/MS\/MS) and accurate mass measurements is undertaken. Plasma, urine, and feces samples were collected after oral administration of PRZ to Sprague\u2013Dawley rats to identify in vivo metabolites. Furthermore, in silico efficacy of the identified metabolites was evaluated by docking study. PRZ at an intraperitoneal dose of 400\u2009mg\/kg showed maximum concentration in the blood to 439.32\u2009\u00b1\u20098.84\u2009ng\/mL at 1\u2009h, while phloretin showed 14.38\u2009\u00b1\u20090.33\u2009ng\/mL at 6\u2009h. The pharmacokinetic profile of PRZ showed that the maximum concentration lies between 1 and 2\u2009h after dosing. Decreased blood glucose levels and maximum excretion of glucose in the urine were observed when the PRZ and metabolites were observed in plasma. The identification and characterization of PRZ metabolites by LC\/ESI\/MS\/MS further revealed that the phase I metabolites of PRZ are hydroxy (mono\u2010, di\u2010, and tri\u2010) and reduction. Phase II metabolites are\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methylated,\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acetylated,\n                    <jats:italic>O<\/jats:italic>\n                    \u2010sulfated, and glucuronide metabolites of PRZ. Further docking study revealed that the metabolites diglucuronide metabolite of mono\u2010hydroxylated PRZ and mono\u2010glucuronidation of PRZ could be considered novel inhibitors of SGLT1 and SGLT2, respectively, which show better binding affinities than their parent compound PRZ and the known inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/jms.4964","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:36:13Z","timestamp":1689726973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A pharmacokinetic study to correlate the hypoglycemic effect of phlorizin in rats: Identification of metabolites as inhibitors of sodium\/glucose cotransporters"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-7688","authenticated-orcid":false,"given":"Roshan M.","family":"Borkar","sequence":"first","affiliation":[{"name":"Analytical Chemistry Division CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"},{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Guwahati India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Kanwal","sequence":"additional","affiliation":[{"name":"Non\u2010Communicable Diseases Group Translational Health Science and Technology Institute (THSTI)  Faridabad India"},{"name":"Department of Pharmacology All India Institute of Medical Sciences  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bandu","family":"Raju","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Division CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Sharanya","family":"Pulimamidi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Guwahati India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneesh Pratim","family":"Das","sequence":"additional","affiliation":[{"name":"Bioinformatics Division ICMR\u2010National Institute of Cancer Prevention and Research  Noida India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash Mohan","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Bioinformatics Division ICMR\u2010National Institute of Cancer Prevention and Research  Noida India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay K.","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Non\u2010Communicable Diseases Group Translational Health Science and Technology Institute (THSTI)  Faridabad India"},{"name":"Department of Biotechnology National Institute of Pharmaceutical Education and Research (NIPER)  Guwahati India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragampeta","family":"Srinivas","sequence":"additional","affiliation":[{"name":"Analytical Chemistry Division CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00195.2002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002\u2010220237"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005\u20102736(69)90108\u20104"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210794455111"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.12.3227"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.110296"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.129825"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07\u20101472"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20101241.2008.01829.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2012.07.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3180"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2RA00373B"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033421\u20107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201004212\u20109"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA08517B"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa971"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.01.056"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13630"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.532"}],"container-title":["Journal 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