{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:40:32Z","timestamp":1792806032808,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32270424"],"award-info":[{"award-number":["32270424"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["2021194"],"award-info":[{"award-number":["2021194"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["2022xkjT045"],"award-info":[{"award-number":["2022xkjT045"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Horizontal Cooperation Topic","award":["32270424"],"award-info":[{"award-number":["32270424"]}]},{"name":"Horizontal Cooperation Topic","award":["2021194"],"award-info":[{"award-number":["2021194"]}]},{"name":"Horizontal Cooperation Topic","award":["2022xkjT045"],"award-info":[{"award-number":["2022xkjT045"]}]},{"name":"Scientific Research Platform Improvement Project of Anhui Medical University","award":["32270424"],"award-info":[{"award-number":["32270424"]}],"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Scientific Research Platform Improvement Project of Anhui Medical University","award":["2021194"],"award-info":[{"award-number":["2021194"]}],"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Scientific Research Platform Improvement Project of Anhui Medical University","award":["2022xkjT045"],"award-info":[{"award-number":["2022xkjT045"]}],"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Chaenomeles speciosa (Sweet) Nakai (C. speciosa) fruit has medicinal and food applications and exhibits beneficial pharmacological properties. This study aimed to explore the hypouricemic effect of C. speciosa fruit extracts on hyperuricemic rats and uncover potential protective mechanisms. The rats were given hypoxanthine (HX, 100 mg\/kg) and potassium oxonate (PO, 300 mg\/kg) for 14 days to induce hyperuricemia. Subsequently, the rats were orally administered C. speciosa fruits total extract (CSFTE, 250, 500, and 1000 mg\/kg) and allopurinol (AP, 10 mg\/kg) one hour after exposure to HX and PO. The results showed that CSFTE had significant xanthine oxidase (XOD) inhibitory activity in vitro (IC50 value of 334.2 \u03bcg\/mL) and exhibited hypouricemic effects in vivo, reducing uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) levels in serum. CSFTE increased UA excretion through the regulation of URAT1, GLUT9, OAT1, and OAT3 protein expression in the kidneys of hyperuricemic rats. Additionally, CSFTE (500 and 1000 mg\/kg) was more effective than AP in improving renal injury and protecting kidney function in hyperuricemic rats. Our study demonstrated that CSFTE effectively reduced UA levels and protected the kidneys by inhibiting XOD expression in vitro and regulating UA, CRE, BUN, URAT1, GLUT9, OAT1, and OAT3 proteins in vivo.<\/jats:p>","DOI":"10.3390\/metabo14020117","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T03:50:27Z","timestamp":1707709827000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Anti-Hyperuricemic Effects of Extracts from Chaenomeles speciosa (Sweet) Nakai Fruits on Hyperuricemic Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Ruoling","family":"Xu","sequence":"first","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Deng","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiren","family":"Ma","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-9283","authenticated-orcid":false,"given":"Fucai","family":"Ren","sequence":"additional","affiliation":[{"name":"Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, 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, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wei, B., Ren, P., Yang, R., Gao, Y., Tang, Q., Xue, C., and Wang, Y. (2023). Ameliorative effect of mannuronate oligosaccharides on hyperuricemic mice via promoting uric acid excretion and modulating gut microbiota. Nutrients, 15.","DOI":"10.3390\/nu15020417"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/CEJ.0b013e328313631a","article-title":"A prospective study of gout and cancer","volume":"18","author":"Boffetta","year":"2009","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101723","DOI":"10.1016\/j.berh.2021.101723","article-title":"Role of diet in hyperuricemia and gout","volume":"35","author":"Danve","year":"2021","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s41256-020-00178-9","article-title":"Geographical distribution of hyperuricemia in mainland China: A comprehensive systematic review and meta-analysis","volume":"5","author":"Huang","year":"2020","journal-title":"Glob. Health Res. Policy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jare.2022.11.003","article-title":"Sulforaphane-driven reprogramming of gut microbiome and metabolome ameliorates the progression of hyperuricemia","volume":"52","author":"Wang","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645879","DOI":"10.3389\/fphar.2021.645879","article-title":"Anti-hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate- and hypoxanthine-induced hyperuricemic mice","volume":"12","author":"Xu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1056\/NEJMoa050373","article-title":"Febuxostat compared with allopurinol in patients with hyperuricemia and gout","volume":"353","author":"Becker","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/14740338.2019.1594771","article-title":"Safety and tolerability of available urate-lowering drugs: A critical review","volume":"18","author":"Strilchuk","year":"2019","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.biopha.2016.07.025","article-title":"Astilbin improves potassium oxonate-induced hyperuricemia and kidney injury through regulating oxidative stress and inflammation response in mice","volume":"83","author":"Wang","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1681\/ASN.2006040415","article-title":"Human renal organic anion transporter 4 operates as an asymmetric urate transporter","volume":"18","author":"Hagos","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1006\/bbrc.2000.2407","article-title":"P-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1","volume":"270","author":"Uchino","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"F327","DOI":"10.1152\/ajprenal.00133.2004","article-title":"Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites","volume":"288","author":"Smeets","year":"2005","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1681\/ASN.2014080793","article-title":"EGF receptor inhibition alleviates hyperuricemic nephropathy","volume":"26","author":"Liu","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","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":"ref_15","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1016\/j.foodchem.2013.06.109","article-title":"Polyphenols and triterpenes from Chaenomeles fruits: Chemical analysis and antioxidant activities assessment","volume":"141","author":"Du","year":"2013","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/pca.3170","article-title":"Rapid authentication of Chaenomeles species by visual volatile components fingerprints based on headspace gas chromatography-ion mobility spectrometry combined with chemometric analysis","volume":"33","author":"Tian","year":"2022","journal-title":"Phytochem. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"H2049","DOI":"10.1111\/1750-3841.13377","article-title":"Chemical composition and bioactivities of two common Chaenomeles fruits in China: Chaenomeles speciosa and Chaenomeles sinensis","volume":"81","author":"Miao","year":"2016","journal-title":"J. Food Sci."},{"key":"ref_18","unstructured":"Chinese Pharmacopeia Commission (2020). Pharmacopoeia of the People\u2019s Republic of China, China Medical Science and Technology Press. [11th ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1021\/acs.jafc.1c00298","article-title":"Bioactivity ingredients of Chaenomeles speciosa against microbes: Characterization by LC-MS and activity evaluation","volume":"69","author":"Wang","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3892\/br.2013.193","article-title":"Chaenomeles speciosa: A review of chemistry and pharmacology","volume":"2","author":"Zhang","year":"2014","journal-title":"Biomed. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9591845","DOI":"10.1155\/2018\/9591845","article-title":"Phytochemical and pharmacological properties of Chaenomeles speciosa: An edible medicinal Chinese Mugua","volume":"2018","author":"Huang","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zheng, X., Wang, H., Zhang, P., Gao, L., Yan, N., Li, P., Liu, X., Du, Y., and Shen, G. (2018). Chemical composition, antioxidant activity and \u03b1-glucosidase inhibitory activity of Chaenomeles Speciosa from four production areas in China. Molecules, 23.","DOI":"10.3390\/molecules23102518"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S1567-5769(03)00051-1","article-title":"Effects and mechanisms of glucosides of Chaenomeles speciosa on collagen-induced arthritis in rats","volume":"3","author":"Chen","year":"2003","journal-title":"Int. Immunopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jep.2012.06.012","article-title":"Pharmacological basis for use of Lychnophora trichocarpha in gouty arthritis: Anti-hyperuricemic and anti-inflammatory effects of its extract, fraction and constituents","volume":"142","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","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":"ref_26","doi-asserted-by":"crossref","unstructured":"Aliyu, A., Shaari, M.R., Ahmad Sayuti, N.S., Reduan, M.F.H., Sithambaram, S., Noordin, M.M., Shaari, K., and Hamzah, H. (2020). Subacute oral administration of Clinacanthus nutans ethanolic leaf extract induced liver and kidney toxicities in ICR mice. Molecules, 25.","DOI":"10.3390\/molecules25112631"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.fct.2014.05.004","article-title":"The methanol extract of Euonymus laxiflorus, Rubia lanceolata and Gardenia jasminoides inhibits xanthine oxidase and reduce serum uric acid level in rats","volume":"70","author":"Liu","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jep.2016.10.001","article-title":"Actions of water extract from Cordyceps militaris in hyperuricemic mice induced by potassium oxonate combined with hypoxanthine","volume":"194","author":"Yong","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1055\/s-0034-1396241","article-title":"Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice","volume":"81","author":"Meng","year":"2015","journal-title":"Planta Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1136\/ard.40.3.245","article-title":"Acute adverse reactions attributed to allopurinol in hospitalised patients","volume":"40","author":"McInnes","year":"1981","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.2174\/092986707781058797","article-title":"Uric acid reduction: A new paradigm in the management of cardiovascular risk?","volume":"14","author":"Dawson","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1291\/hypres.24.691","article-title":"Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects","volume":"24","author":"Iseki","year":"2001","journal-title":"Hypertens. Res."},{"key":"ref_33","first-page":"1501","article-title":"The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study","volume":"27","author":"Lin","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/S0272-6386(04)00934-5","article-title":"Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort","volume":"44","author":"Iseki","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1161\/01.ATV.0000161274.87407.26","article-title":"Association between serum uric acid, metabolic syndrome, and carotid atherosclerosis in Japanese individuals","volume":"25","author":"Ishizaka","year":"2005","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s11926-996-0044-0","article-title":"Renal urate handling: Clinical relevance of recent advances","volume":"7","author":"Anzai","year":"2005","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1021\/cr400443z","article-title":"The mononuclear molybdenum enzymes","volume":"114","author":"Hille","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1055\/s-2002-20262","article-title":"Aesculin possesses potent hypouricemic action in rodents but is devoid of xanthine oxidase\/dehydrogenase inhibitory activity","volume":"68","author":"Kong","year":"2002","journal-title":"Planta Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3389\/fphar.2017.00996","article-title":"Hypouricemic effects of Ganoderma applanatum in hyperuricemia mice through OAT1 and GLUT9","volume":"8","author":"Yong","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.tox.2010.08.013","article-title":"Evaluation of a urinary kidney biomarker panel in rat models of acute and subchronic nephrotoxicity","volume":"277","author":"Hoffmann","year":"2010","journal-title":"Toxicology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jep.2018.05.002","article-title":"Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic applications of Alpinia oxyphylla Miquel: A review","volume":"224","author":"Zhang","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1248\/bpb.b15-00402","article-title":"Mangiferin inhibits renal urate reabsorption by modulating urate transporters in experimental hyperuricemia","volume":"38","author":"Yang","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1039\/C8FO02124D","article-title":"Hypouricemic and nephroprotective roles of anthocyanins in hyperuricemic mice","volume":"10","author":"Qian","year":"2019","journal-title":"Food Funct."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1136\/ard.60.10.981","article-title":"Relation between adverse events associated with allopurinol and renal function in patients with gout","volume":"60","author":"Morales","year":"2001","journal-title":"Ann. Rheum. Dis."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/2\/117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:58:25Z","timestamp":1760104705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/2\/117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,10]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["metabo14020117"],"URL":"https:\/\/doi.org\/10.3390\/metabo14020117","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,10]]}}}