{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:13:45Z","timestamp":1790475225197,"version":"4.1.0"},"reference-count":38,"publisher":"Georg Thieme Verlag KG","issue":"10\/11","funder":[{"name":"Korea Institute of Science and Technology Intramural Research Grant","award":["2E32702"],"award-info":[{"award-number":["2E32702"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2021R1F1A1049427"],"award-info":[{"award-number":["NRF-2021R1F1A1049427"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Saikosaponins, bioactive compounds derived from Bupleurum falcatum roots, have limited applications due to their low bioavailability and the absence of efficient large-scale separation methods. To address this, an enzymatic transformation in vitro with cellulase was employed to remove glucose at the C-3 position, producing lipophilic prosaikogenins. These metabolites were separated using countercurrent chromatography (CCC) and preparative HPLC. The optimal CCC solvent system was determined to be dichloromethane\/methanol\/water (4\u200a:\u200a3\u200a:\u200a2, v\/v\/v). Prosaikogenin F and prosaikogenin G (PSG G) were isolated from the deglycosylated fraction, and the effect of rotation speed on compound retention was examined. Further enzymatic biotransformation using \u03b1-L-rhamnosidase and cellulase resulted in the isolation of prosaikogenins E1 and E3. The efficient separation of these four prosaikogenins was achieved through a combination of enzymatic\n          transformation and CCC. Of these, PSG G demonstrated the strongest anticancer activity against the cancer cell lines MDA-MB-468, HepG2, and HCT116, while exhibiting lower toxicity in normal cells, supporting its potential as an effective anticancer agent. This study presents a highly efficient enzymatic transformation and separation strategy that can aid in the pharmaceutical development of saikosaponin derivatives.<\/jats:p>","DOI":"10.1055\/a-2592-0968","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T19:59:44Z","timestamp":1749585584000},"page":"590-598","source":"Crossref","is-referenced-by-count":1,"title":["Separation and Cytotoxicity of Enzymatic Transformed Prosaikogenins from Bupleurum falcatum"],"prefix":"10.1055","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-0304","authenticated-orcid":false,"given":"Hyejin","family":"Ko","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea"},{"name":"Natural Product Drug Development Division, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangho","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea"},{"name":"Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Jin","family":"Ha","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-3925","authenticated-orcid":false,"given":"Yeong Shik","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.2042-7158.2010.01170.x","article-title":"Genus Bupleurum: A review of its phytochemistry, pharmacology and modes of action","volume":"63","author":"M L Ashour","year":"2011","journal-title":"J Pharm Pharmacol"},{"key":"ref2","first-page":"245","article-title":"Traditional use, pharmacology, toxicology, and quality control of species in genus Bupleurum L","volume":"5","author":"R Y Yao","year":"2013","journal-title":"Chin Herb 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Immunopharmacol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00011-019-01284-2","article-title":"Saikosaponin C exerts anti-HBV effects by attenuating HNF1\u03b1 and HNF4\u03b1 expression to suppress HBV pgRNA synthesis","volume":"68","author":"Y Pan","year":"2019","journal-title":"Inflamm Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.phymed.2018.09.174","article-title":"A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins","volume":"50","author":"X Li","year":"2018","journal-title":"Phytomedicine"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s12906-023-04108-3","article-title":"The potential effect and mechanism of Saikosaponin A against gastric cancer","volume":"23","author":"C Wang","year":"2023","journal-title":"BMC Complement Med 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Lai","year":"2020","journal-title":"Onco Targets Ther"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.lfs.2004.10.003","article-title":"Saikosaponin C induces endothelial cells growth, migration and capillary tube formation","volume":"76","author":"K G Shyu","year":"2004","journal-title":"Life Sci"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1124\/dmd.112.048975","article-title":"Metabolism of saikosaponin a in rats: Diverse oxidations on the aglycone moiety in liver and intestine in addition to hydrolysis of glycosidic bonds","volume":"41","author":"G Liu","year":"2013","journal-title":"Drug Metab Dispos"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/BF02973933","article-title":"Metabolism of saikosaponin c and naringin by human intestinal bacteria","volume":"20","author":"K U Yu","year":"1997","journal-title":"Arch Pharm Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"104844","DOI":"10.1016\/j.bioorg.2021.104844","article-title":"Ginsenoside derivatives inhibit advanced glycation end-product formation and glucose-fructose mediated protein glycation in vitro via a specific structure-activity relationship","volume":"111","author":"M Yousof Ali","year":"2021","journal-title":"Bioorg Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1055\/s-0032-1328401","article-title":"Antiproliferative and apoptotic activities of triterpenoid saponins from the roots of Platycodon grandiflorum and their structure-activity relationships","volume":"79","author":"J Chun","year":"2013","journal-title":"Planta Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jgr.2014.02.002","article-title":"Changes in ginsenoside compositions and antioxidant activities of hydroponic-cultured ginseng roots and leaves with heating 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Kostanyan","year":"2020","journal-title":"Molecules"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"460576","DOI":"10.1016\/j.chroma.2019.460576","article-title":"Hydrophobic and hydrophilic interactions in countercurrent chromatography","volume":"1611","author":"L Zhang","year":"2020","journal-title":"J Chromatogr A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.aca.2015.04.055","article-title":"Tubing modifications for countercurrent chromatography (CCC): Stationary phase retention and separation efficiency","volume":"884","author":"M Englert","year":"2015","journal-title":"Anal Chim Acta"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.chroma.2011.12.036","article-title":"Overlapping elution-extrusion counter-current chromatography: A novel method for efficient purification of natural cytotoxic andrographolides from Andrographis paniculate","volume":"1223","author":"D Wu","year":"2012","journal-title":"J Chromatogr A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1002\/jssc.201400871","article-title":"Separation of triterpenoid saponins from the root of Bupleurum falcatum by countercurrent chromatography: The relationship between the partition coefficients and solvent system composition","volume":"37","author":"K J Lee","year":"2014","journal-title":"J Sep Sci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"463776","DOI":"10.1016\/j.chroma.2023.463776","article-title":"The secret of reversed-phase\/weak cation exchange retention mechanisms in mixed-mode liquid chromatography applied for small drug molecule analysis","volume":"1690","author":"B Svrkota","year":"2023","journal-title":"J Chromatogr A"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"462209","DOI":"10.1016\/j.chroma.2021.462209","article-title":"Reversed-phase and weak anion-exchange mixed-mode stationary phase for fast separation of 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