{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:25:44Z","timestamp":1787027144372,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hyperuricemia (HUA), characterized by persistently elevated serum uric acid (UA), represents a growing global public-health concern. Current urate-lowering medications are often associated with hepatotoxicity and nephrotoxicity, highlighting the urgent need for safer, food-derived alternatives.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A macroporous resin-purified fraction (PLE-2) from\n                      <jats:italic>Paeonia lactiflora<\/jats:italic>\n                      Pall. root extract was characterized by HPLC fingerprinting and evaluated in HK-2 human renal proximal tubular epithelial cells and a potassium oxonate\/hypoxanthine-induced rat model of HUA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      , PLE-2 exhibited significant cytoprotective activity against UA-induced injury.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , oral administration of PLE-2 (100, 200, and 400 mg\/kg) dose-dependently reduced serum UA levels to ranges comparable with allopurinol, while attenuating renal injury (decreased creatinine and blood urea nitrogen, improved kidney histology). The mechanism involves dual regulation: suppression of hepatic UA production via inhibition of xanthine oxidase (XOD) and adenosine deaminase (ADA), and enhancement of renal UA excretion through downregulation of reabsorption transporters (URAT1, GLUT9) and upregulation of secretion transporters (OAT1, OAT3, ABCG2), confirmed by qPCR and Western blot. Molecular docking showed strong binding of paeoniflorin (the major metabolite in PLE-2) to these targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>PLE-2 demonstrates potent dual action on UA synthesis and excretion with notable nephroprotective effects, positioning the purified fraction as a promising functional food metabolite for preventing and ameliorating HUA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1800063","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:33:29Z","timestamp":1775540009000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dual mechanisms of a purified root extract of Paeonia lactiflora Pall. in regulating uric acid homeostasis: inhibition of hepatic synthesis and promotion of renal excretion in hyperuricemic rat models"],"prefix":"10.3389","volume":"17","author":[{"given":"Tingting","family":"Jin","sequence":"first","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoling","family":"Xu","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juncheng","family":"Ma","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113910","DOI":"10.1016\/j.jep.2021.113910","article-title":"Review on the genus Brugmansia: traditional usage, phytochemistry, pharmacology, and toxicity","volume":"279","author":"Algradi","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1096\/fj.14-269043","article-title":"Translating dosages from animal models to human clinical trials--revisiting body surface area scaling","volume":"29","author":"Blanchard","year":"2015","journal-title":"Faseb J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1053\/j.ackd.2012.07.009","article-title":"Renal transport of uric acid: evolving concepts and uncertainties","volume":"19","author":"Bobulescu","year":"2012","journal-title":"Adv. Chronic Kidney Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1021\/acs.jcim.0c01227","article-title":"Toward an understanding of pan-assay interference compounds and promiscuity: a structural perspective on binding modes","volume":"61","author":"Bolz","year":"2021","journal-title":"J. Chem. Inf. Model"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.3892\/ijmm.2020.4512","article-title":"Construction and expression of recombinant uricase-expressing genetically engineered bacteria and its application in rat model of hyperuricemia","volume":"45","author":"Cai","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jep.2015.08.043","article-title":"Green tea polyphenols decreases uric acid level through xanthine oxidase and renal urate transporters in hyperuricemic mice","volume":"175","author":"Chen","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1016\/s0140-6736(16)00346-9","article-title":"Gout","volume":"388","author":"Dalbeth","year":"2016","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"6678","DOI":"10.3390\/ijms22136678","article-title":"The role of ABCG2 in the pathogenesis of primary hyperuricemia and Gout-An update","volume":"22","author":"Eckenstaler","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nature742","article-title":"Molecular identification of a renal urate anion exchanger that regulates blood urate levels","volume":"417","author":"Enomoto","year":"2002","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"12169","DOI":"10.1039\/d4fo03481c","article-title":"Mulberry (Fructus mori) extract alleviates hyperuricemia by regulating urate transporters and modulating the gut microbiota","volume":"15","author":"Fang","year":"2024","journal-title":"Food Funct."},{"key":"B11","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1002\/art.41247","article-title":"2020 American college of rheumatology guideline for the management of gout","volume":"72","author":"FitzGerald","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"108723","DOI":"10.1016\/j.pharmthera.2024.108723","article-title":"Organic anion transporters in remote sensing and organ crosstalk","volume":"263","author":"Granados","year":"2024","journal-title":"Pharmacology and Therapeutics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"156037","DOI":"10.1016\/j.phymed.2024.156037","article-title":"Paeoniae radix alba improved intestinal mucosal microcirculation disturbance by regulating lncRNA MALAT1\/HIF-1\u03b1 pathway in the treatment of ulcerative colitis","volume":"135","author":"Gu","year":"2024","journal-title":"Phytomedicine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1038\/s41401-024-01459-6","article-title":"Therapeutic potential and pharmacological mechanisms of traditional Chinese medicine in gout treatment","volume":"46","author":"Guo","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1142\/s0192415x25500582","article-title":"Paeoniflorin alleviates metabolic dysfunction-associated fatty liver disease by targeting STING-mediated pyroptosis via inhibiting the NLRP3 inflammasome","volume":"53","author":"Guo","year":"2025","journal-title":"Am. J. Chin. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/0024-3205(90)90507-n","article-title":"Substituted cyclic imides as potential anti-gout agents","volume":"46","author":"Hall","year":"1990","journal-title":"Life Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.jep.2013.08.017","article-title":"Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type I collagen","volume":"149","author":"Ji","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"113054","DOI":"10.1016\/j.jep.2020.113054","article-title":"Total glucosides of herbaceous peony (Paeonia lactiflora Pall.) flower attenuate adenine- and ethambutol-induced hyperuricaemia in rats","volume":"261","author":"Kang","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1016\/j.jep.2020.113708","article-title":"Update on the epidemiology, genetics, and therapeutic options of hyperuricemia","volume":"12","author":"Li","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"113708","DOI":"10.1016\/j.jep.2020.113708","article-title":"Genus paeonia: a comprehensive review on traditional uses, phytochemistry, pharmacological activities, clinical application, and toxicology","volume":"269","author":"Li","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"157115","DOI":"10.1016\/j.phymed.2025.157115","article-title":"Puerarin-rich compound Puerariae lobatae formulas alleviate hyperuricemia in mice by enhancing renal and intestinal function through regulating gut microbiota","volume":"146","author":"Li","year":"2025","journal-title":"Phytomedicine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.3390\/ph17111507","article-title":"The therapeutic management of chemical and herbal medications on uric acid levels and gout: modern and traditional wisdom","volume":"17","author":"Lin","year":"2024","journal-title":"Pharm. (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"18758","DOI":"10.1021\/acs.jafc.4c03605","article-title":"Harnessing protein hydrolysates and peptides for hyperuricemia management: insights into sources, mechanisms, techniques, and future directions","volume":"72","author":"Liu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"130610","DOI":"10.1016\/j.foodchem.2021.130610","article-title":"Ingredients with anti-inflammatory effect from medicine food homology plants","volume":"368","author":"Lu","year":"2022","journal-title":"Food Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/978-1-0716-1468-6_15","article-title":"Identification of pan-assay INterference compoundS (PAINS) using an MD-Based protocol","volume":"2315","author":"Magalh\u00e3es","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijcard.2015.08.109","article-title":"Regulation of uric acid metabolism and excretion","volume":"213","author":"Maiuolo","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev-physiol-021113-170343","article-title":"The molecular physiology of uric acid homeostasis","volume":"77","author":"Mandal","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1080\/10408398.2017.1412939","article-title":"Management of hyperuricemia through dietary polyphenols as a natural medicament: a comprehensive review","volume":"59","author":"Mehmood","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"9010","DOI":"10.1038\/s41598-024-58506-9","article-title":"Deep-learning model for evaluating histopathology of acute renal tubular injury","volume":"14","author":"Nguyen","year":"2024","journal-title":"Sci. Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/nrd4461","article-title":"What do drug transporters really do?","volume":"14","author":"Nigam","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"B29","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3892\/etm.2020.9498","article-title":"Naringin attenuates renal interstitial fibrosis by regulating the TGF-\u03b2\/Smad signaling pathway and inflammation","volume":"21","author":"Wang","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"10338","DOI":"10.1073\/pnas.0901249106","article-title":"Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout","volume":"106","author":"Woodward","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B30","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s13105-015-0399-7","article-title":"Uric acid crystal could inhibit Numb-induced URAT1 lysosome degradation in uric acid nephropathy","volume":"71","author":"Wu","year":"2015","journal-title":"J. Physiol. Biochem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1897211","article-title":"Limosilactobacillus fermentum JL-3 isolated from \u201cJiangshui\u201d ameliorates hyperuricemia by degrading uric acid","volume":"13","author":"Wu","year":"2021","journal-title":"Gut Microbes"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1093\/rheumatology\/keq096","article-title":"The rs2231142 variant of the ABCG2 gene is associated with uric acid levels and gout among Japanese people","volume":"49","author":"Yamagishi","year":"2010","journal-title":"Rheumatology (Oxford)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"22113","DOI":"10.1039\/d4ra03419h","article-title":"In vitro evaluation and in situ intestinal absorption characterisation of paeoniflorin nanoparticles in a rat model","volume":"14","author":"Xiao","year":"2024","journal-title":"RSC Adv."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2582","DOI":"10.1039\/c4fo00287c","article-title":"Inhibition of flavonoids on acetylcholine esterase: binding and structure-activity relationship","volume":"5","author":"Xie","year":"2014","journal-title":"Food Funct."},{"key":"B34","doi-asserted-by":"publisher","first-page":"107452","DOI":"10.1016\/j.pharmthera.2019.107452","article-title":"Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony","volume":"207","author":"Zhang","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"5778","DOI":"10.1039\/c8fo01480a","article-title":"Anti-hyperuricemic and nephroprotective effects of extracts from Chaenomeles sinensis (Thouin) koehne in hyperuricemic mice","volume":"9","author":"Zhang","year":"2018","journal-title":"Food Funct."},{"key":"B36","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.nefro.2021.09.010","article-title":"NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt\/\u03b2-catenin pathway in HK-2 cells","volume":"43","author":"Zhang","year":"2023","journal-title":"Nefrol. Engl. Ed."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1800063\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:33:30Z","timestamp":1775540010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1800063\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":40,"alternative-id":["10.3389\/fphar.2026.1800063"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1800063","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"article-number":"1800063"}}