{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:10:35Z","timestamp":1787965835728,"version":"build-2784847793"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cudrania tricuspidata Bureau (Moraceae) shows numerous pharmacological effects and has been used in traditional herbal remedies for inflammation, gastritis, tumors, and liver diseases. However, no validated analytical method for the standardization and optimization of the biological properties of C. tricuspidata preparations has been reported. We developed and validated a reverse-phase high-performance liquid chromatography (HPLC) method for the separation and quantification of active markers. Ethanolic extracts of C. tricuspidata leaves were prepared and evaluated for chemical profiles and biological activities. The 80% ethanolic extract demonstrated the greatest antioxidant activity and phenolic content, while the 100% ethanolic extract had the greatest total flavonoid content and xanthine oxidase (XO) inhibitory activity. The validated HPLC method confirmed that chlorogenic acid, rutin, and kaempferol were present in C. tricuspidata leaf extracts. We postulated that the antioxidant and anti-hyperuricemic\/gout effects of C. tricuspidata extract could be attributed to these marker compounds. Our results suggested that the flavonoid-rich fraction of the leaf extract may be utilized for the treatment and prevention of hyperuricemia-related diseases, and the validated method and marker compounds could be applied for the quality control of C. tricuspidata preparations.<\/jats:p>","DOI":"10.3390\/molecules22091489","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T13:59:10Z","timestamp":1504792750000},"page":"1489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Quantitative Analysis, Extraction Optimization, and Biological Evaluation of Cudrania tricuspidata Leaf and Fruit Extracts"],"prefix":"10.3390","volume":"22","author":[{"given":"Seung-Hui","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 58554, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung","family":"Ki","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Hun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Nursing, Dongshin University, Naju-si, Jeonnam 58245, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Seop","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 58554, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Dai","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Business Administration, Mokpo National University, Muan-gun, Jeonnam 58554, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-5723","authenticated-orcid":false,"given":"In-Soo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-0529","authenticated-orcid":false,"given":"Seung-Sik","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 58554, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1211\/jpp.60.9.0015","article-title":"Anti-inflammatory action of Cudrania tricuspidata on spleen cell and T lymphocyte proliferation","volume":"60","author":"Chang","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1016\/j.bmcl.2006.08.032","article-title":"Anti-atherosclerotic and anti-inflammatory activities of catecholic xanthones and flavonoids isolated from Cudrania tricuspidata","volume":"16","author":"Park","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.intimp.2008.11.008","article-title":"Cudratricusxanthone A from Cudrania tricuspidata suppresses pro-inflammatory mediators through expression of anti-inflammatory heme oxygenase-1 in RAW264.7 macrophages","volume":"9","author":"Jeong","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s12272-009-1135-z","article-title":"Antioxidant activities of new flavonoids from Cudrania tricuspidata root bark","volume":"32","author":"Lee","year":"2009","journal-title":"Arch. Pharm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1021\/acs.jnatprod.6b00204","article-title":"Chemical constituents isolated from the root bark of Cudrania tricuspidata and their potential neuroprotective effects","volume":"79","author":"Kwon","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/BF02975134","article-title":"Hepatoprotective constituents of Cudrania tricuspidata","volume":"28","author":"Tian","year":"2005","journal-title":"Arch. Pharm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1016\/j.bmcl.2005.08.099","article-title":"Antioxidant and cytotoxic activities of xanthones from Cudrania tricuspidata","volume":"15","author":"Lee","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.phytochem.2014.10.021","article-title":"Isoflavones with neuroprotective activities from fruits of Cudrania tricuspidata","volume":"111","author":"Hiep","year":"2015","journal-title":"Phytochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/ptr.3577","article-title":"The fruits of Cudrania tricuspidata suppress development of atopic dermatitis in NC\/Nga mice","volume":"26","author":"Lee","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1021\/np800418j","article-title":"Prenylated and benzylated flavonoids from the fruits of Cudrania tricuspidata","volume":"72","author":"Han","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jo, Y.H., Kim, S.B., Liu, Q., Do, S.-G., Hwang, B.Y., and Lee, M.K. (2017). Comparison of pancreatic lipase inhibitory isoflavonoids from unripe and ripe fruits of Cudrania tricuspidata. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172069"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1021\/acs.jafc.5b00903","article-title":"Effects of Cudrania tricuspidata fruit extract and its active compound, 5,7,3\u2032,4\u2032-tetrahydroxy-6,8-diprenylisoflavone, on the high-affinity IgE receptor-mediated activation of Syk in mast cells","volume":"63","author":"Lee","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1007\/BF02977895","article-title":"Monoamine oxidase inhibitory constituents from the fruits of Cudrania tricuspidata","volume":"28","author":"Han","year":"2005","journal-title":"Arch. Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10480","DOI":"10.3390\/nu7125544","article-title":"Anti-obesity effect of 6,8-diprenylgenistein, an isoflavonoid of Cudrania tricuspidata fruits in high-fat diet-induced obese mice","volume":"7","author":"Jo","year":"2015","journal-title":"Nutrients"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kim, O.-K., Nam, D.-E., Jun, W., and Lee, J. (2015). Cudrania tricuspidata water extract improved obesity-induced hepatic insulin resistance in db\/db mice by suppressing ER stress and inflammation. Food Nutr. Res., 59.","DOI":"10.3402\/fnr.v59.29165"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Seo, J.-H., Kim, J.-E., Shim, J.-H., Yoon, G., Bang, M., Bae, C.-S., Lee, K.-J., Park, D.-H., and Cho, S.-S. (2016). HPLC analysis, optimization of extraction conditions and biological evaluation of Corylopsis coreana Uyeki Flos. Molecules, 21.","DOI":"10.3390\/molecules21010094"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.clnu.2016.03.002","article-title":"Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress","volume":"35","author":"Shi","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/1756-0500-5-158","article-title":"Antimicrobial and antioxidant activity of kaempferol rhamnoside derivatives from Bryophyllum pinnatum","volume":"5","author":"Tatsimo","year":"2012","journal-title":"BMC Res. Notes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/sj.ejcn.1601090","article-title":"Bioavailiability and efficiency of rutin as an antioxidant: A human supplementation study","volume":"54","author":"Boyle","year":"2000","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1111\/jphp.12626","article-title":"Effects of extracts from Corylopsis coreana Uyeki (Hamamelidaceae) flos on xanthine oxidase activity and hyperuricemia","volume":"68","author":"Yoon","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Citraro, R., Navarra, M., Leo, A., Donato Di Paola, E., Santangelo, E., Lippiello, P., Aiello, R., Russo, E., and De Sarro, G. (2016). The anticonvulsant activity of a flavonoid-rich extract from orange juice involves both NMDA and GABA-benzodiazepine receptor complexes. Molecules, 21.","DOI":"10.3390\/molecules21091261"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3389\/fphar.2016.00288","article-title":"Hypoglycemic activity and the potential mechanism of the flavonoid rich extract from Sophora tonkinensis Gagnep. in KK-Ay mice","volume":"7","author":"Huang","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22102","DOI":"10.3390\/molecules201219835","article-title":"Safety evaluation, in vitro and in vivo antioxidant activity of the flavonoid-rich extract from Maydis stigma","volume":"20","author":"Peng","year":"2015","journal-title":"Molecules"},{"key":"ref_24","first-page":"3367","article-title":"Flavonoid rich extract of Murraya koenigii alleviates in-vitro LDL oxidation and oxidized LDL induced apoptosis in raw 264.7 Murine macrophage cells","volume":"52","author":"Gajaria","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11816","DOI":"10.3390\/molecules190811816","article-title":"Potent effects of flavonoid-rich extract from Rosa laevigata Michx fruit against hydrogen peroxide-induced damage in PC12 cells via attenuation of oxidative stress, inflammation and apoptosis","volume":"19","author":"Liu","year":"2014","journal-title":"Molecules"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4097195","DOI":"10.1155\/2017\/4097195","article-title":"In vitro and in vivo studies on Quercus acuta Thunb. (Fagaceae) extract: Active constituents, serum uric acid suppression, and xanthine oxidase inhibitory activity","volume":"2017","author":"Yoon","year":"2017","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.3892\/ijmm.2017.2973","article-title":"Identification of the biologically active constituents of Camellia japonica leaf and anti-hyperuricemic effect in vitro and in vivo","volume":"39","author":"Yoon","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jsps.2016.04.025","article-title":"The pharmacological potential of rutin","volume":"25","author":"Ganeshpurkar","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000351703","article-title":"Beneficial effect of rutin on oxonate-induced hyperuricemia and renal dysfunction in mice","volume":"92","author":"Chen","year":"2013","journal-title":"Pharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jep.2004.03.037","article-title":"Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver","volume":"93","author":"Zhu","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00210-015-1110-9","article-title":"Experimental colitis in mice is attenuated by topical administration of chlorogenic acid","volume":"388","author":"Zatorski","year":"2015","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1142\/S0192415X1450092X","article-title":"Study on the anti-gout activity of Chlorogenic acid: Improvement on hyperuricemia and gouty inflammation","volume":"42","author":"Meng","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00011-013-0674-4","article-title":"Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells","volume":"63","author":"Hwang","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.intimp.2010.07.005","article-title":"Chlorogenic acid suppresses pulmonary eosinophilia, IgE production, and Th2-type cytokine production in an ovalbumin-induced allergic asthma: Activation of STAT-6 and JNK is inhibited by chlorogenic acid","volume":"10","author":"Kim","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1021\/jf505584m","article-title":"Novel insights into the inhibitory mechanism of kaempferol on xanthine oxidase","volume":"63","author":"Wang","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","first-page":"121","article-title":"Antiinflammatory and antiulcer effects of kaempferol, a flavone, isolated from Rhamnus procumbens","volume":"26","author":"Goel","year":"1988","journal-title":"Indian J. Exp. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1271\/bbb.63.1787","article-title":"Inhibition of xanthine oxidase by flavonoids","volume":"63","author":"Nagao","year":"1999","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s40005-016-0262-z","article-title":"Novel LC\u2013MS\/MS method for estimation of niacin with negligible matrix effect and its application to the BE study","volume":"47","author":"Vats","year":"2017","journal-title":"J. Pharm. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s40005-017-0305-0","article-title":"Fast and simple gas chromatographic method for simultaneous estimation of camphor, menthol and methyl salicylate in analgesic ointment: Application in stability study","volume":"47","author":"Adib","year":"2017","journal-title":"J. Pharm. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1590\/S0102-695X2013000100008","article-title":"Development and validation of a HPLC method for the quantification of three flavonoids in a crude extract of Dimorphandra gardneriana","volume":"23","author":"Landim","year":"2013","journal-title":"Rev. Bras. Farmacogn."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/9\/1489\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:44:21Z","timestamp":1760208261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/9\/1489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,7]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9]]}},"alternative-id":["molecules22091489"],"URL":"https:\/\/doi.org\/10.3390\/molecules22091489","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,7]]}}}