{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:17:30Z","timestamp":1772813850894,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Korea Institute of Oriental Medicine (KIOM) from the Ministry of Science and ICT, Republic of Korea","award":["K17281 and K18101"],"award-info":[{"award-number":["K17281 and K18101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Platelets are an important component of the initial response to vascular endothelial injury; however, platelet dysfunction induces the acute clinical symptoms of thrombotic disorders, which trigger severe cardiovascular diseases such as myocardial infarction, ischemia, and stroke. In this study, we investigated the Dryopteris crassirhizoma\u2019s antiplatelet activity. A water extract of D. crassirhizoma (WDC) was partitioned into dichloromethane (DCM), ethyl acetate, n-butyl alcohol, and water. Among these four fractions, the DCM fraction potently inhibited the collagen-stimulated platelet aggregation in a concentration-dependent manner. From this fraction, five different acylphloroglucinol compounds and one flavonoid were isolated by activity-guided column chromatography. They were identified by comparing their mass, 1H-, and 13C-NMR spectral data with those reported in the literature. Quantifying the six compounds in WDC and its DCM fraction by high-performance liquid chromatography (HPLC) revealed that butyryl-3-methylphloroglucinol (compound 4) was the most abundant in these samples. Additionally, butyryl-3-methylphloroglucinol showed the strongest inhibitory activity in the collagen- and arachidonic acid (AA)-induced platelet aggregation, with inhibition ratios of 92.36% and 89.51% in the collagen and AA-induced platelet aggregation, respectively, without cytotoxicity. On the active concentrations, butyryl-3-methylphloroglucinol significantly suppressed the convulxin-induced platelet activation. Regarding the structure\u2013activity relationships for the five acylphloroglucinol compounds, our results demonstrated that the functional butanonyl, methoxy, and hydroxy groups in butyryl-3-methylphloroglucinol play important roles in antiplatelet activity. The findings indicate that acylphloroglucinols, including butyryl-3-methylphloroglucinol from D. crassirhizom, possess an antiplatelet activity, supporting the use of this species for antiplatelet remedies.<\/jats:p>","DOI":"10.3390\/molecules24122212","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T11:15:58Z","timestamp":1560424558000},"page":"2212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antiplatelet Activity of Acylphloroglucinol Derivatives Isolated from Dryopteris crassirhizoma"],"prefix":"10.3390","volume":"24","author":[{"given":"Nam-Hui","family":"Yim","sequence":"first","affiliation":[{"name":"Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Myungmoon Bio. Co., Ltd., 180 Yuram-ro, Dong-gu, Daegu 41059, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"BoHyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"ViroMed Co., Ltd., Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7272-7290","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Yeul","family":"Ma","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yang, X. (2003). Encyclopedic Reference of Traditional Chinese Medicine, Springer-Verl.","DOI":"10.1007\/978-3-662-05177-1"},{"key":"ref_2","unstructured":"Zhong Hua Ben Cao Commision (1985). Zhong Hua Ben Cao (Materia Medica of China), Shanhai Technology Press. [2nd ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1016\/j.phytochem.2008.07.017","article-title":"Dammaradiene synthase, a squalene cyclase, from Dryopteris crassirhizoma Nakai","volume":"69","author":"Shinozaki","year":"2008","journal-title":"Phytochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s00436-011-2592-0","article-title":"In vivo anthelmintic activity of Dryopteris crassirhizoma, Kochia scoparia, and Polygala tenuifolia against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus)","volume":"110","author":"Lu","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1248\/bpb.26.1354","article-title":"Antioxidant Activity of Two Phloroglucinol Derivatives from Dryopteris crassirhizoma","volume":"26","author":"Lee","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4738","DOI":"10.1016\/j.bmcl.2006.07.018","article-title":"Fatty acid synthase inhibitory activity of acylphloroglucinols isolated from Dryopteris crassirhizoma","volume":"16","author":"Na","year":"2006","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, J., Yan, Y.T., Fu, S.Z., Peng, B., Bao, L.L., Zhang, Y.L., Hu, J.H., Zeng, Z.P., Geng, D.H., and Gao, Z.P. (2017). Anti-Influenza Virus (H5N1) Activity Screening on the Phloroglucinols from Rhizomes of Dryopteris crassirhizoma. Molecules, 22.","DOI":"10.3390\/molecules22030431"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s12272-009-1502-9","article-title":"Antibacterial activity of two phloroglucinols, flavaspidic acids AB and PB, from Dryopteris crassirhizoma","volume":"32","author":"Lee","year":"2009","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jep.2012.11.019","article-title":"ERK1- and TBK1-targeted anti-inflammatory activity of an ethanol extract of Dryopteris crassirhizoma","volume":"145","author":"Yang","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jep.2010.04.038","article-title":"Dryopteris crassirhizoma has anti-cancer effects through both extrinsic and intrinsic apoptotic pathways and G0\/G1 phase arrest in human prostate cancer cells","volume":"130","author":"Chang","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1155\/2013\/852648","article-title":"Water Extract of Dryopteris crassirhizoma Attenuates Bone Loss by Suppressing Osteoclast Differentiation and Function","volume":"2013","author":"Ha","year":"2013","journal-title":"Evid.-Based Complementary Altern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1248\/cpb.54.748","article-title":"Phenolic Constituents from the Rhizomes of Dryopteris crassirhizoma","volume":"54","author":"Chang","year":"2006","journal-title":"Chem. Pharm. Bull."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1248\/cpb.56.711","article-title":"Two New Triterpenes from the Rhizome of Dryopteris crassirhizoma, and Inhibitory Activities of Its Constituents on Human Immunodeficiency Virus-1 Protease","volume":"56","author":"Lee","year":"2008","journal-title":"Chem. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.phytol.2008.09.005","article-title":"Phytochemical investigation of the rhizomes of Dryopteris crassirhizoma","volume":"1","author":"Gao","year":"2008","journal-title":"Phytochem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bmc.2006.10.006","article-title":"Antiprotozoal and antimicrobial activities of O-alkylated and formylated acylphloroglucinols","volume":"15","author":"Bharate","year":"2007","journal-title":"Bioorganic Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1152\/physrev.1990.70.4.1177","article-title":"Developmental mechanisms underlying pathology of arteries","volume":"70","author":"Schwartz","year":"1990","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18S","DOI":"10.1378\/chest.124.3_suppl.18S","article-title":"Thrombin and Platelet Activation","volume":"124","author":"Brass","year":"2003","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1345\/aph.10381","article-title":"Antiplatelet agents for secondary prevention of ischemic stroke","volume":"35","author":"Majid","year":"2001","journal-title":"Ann. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nm1102-1227","article-title":"Platelets in atherothrombosis","volume":"8","author":"Ruggeri","year":"2002","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/292367a0","article-title":"The phosphatidylinositol cycle and the regulation of arachidonic acid production","volume":"292","author":"Lapetina","year":"1981","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7314","DOI":"10.1016\/S0021-9258(18)34378-3","article-title":"Platelet-activating factor stimulates the phosphatidylinositol cycle. Appearance of phosphatidic acid is associated with the release of serotonin in horse platelets","volume":"257","author":"Lapetina","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11856","DOI":"10.1016\/S0021-9258(18)33641-X","article-title":"Evidence for multiple metabolic pools of phosphatidylinositol in stimulated platelets","volume":"257","author":"Billah","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1073\/pnas.76.7.3238","article-title":"Diglyceride lipase: A pathway for arachidonate release from human platelets","volume":"76","author":"Bell","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/S0031-9422(97)01003-0","article-title":"Acylphloroglucinols and flavonoid aglycones produced by external glands on the leaves of two dryopteris ferns and currania robertiana","volume":"48","author":"Wollenweber","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_25","first-page":"177","article-title":"Chemical constituents in roots of Dryopteris championii","volume":"36","author":"Zuo","year":"2005","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1590\/S0102-695X2010005000006","article-title":"Flavanones from aerial parts of Cordia globosa (Jacq.) Kunth, Boraginaceae","volume":"20","author":"Silva","year":"2010","journal-title":"Rev. Bras. De Farmacogn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34437","DOI":"10.1074\/jbc.273.51.34437","article-title":"The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor gamma-chain and linker for activitor of T cells (LAT) in platelets stimulated by collagen and convulxin","volume":"273","author":"Gibbins","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.fct.2011.04.003","article-title":"Antithrombotic and profibrinolytic activities of phloroglucinol","volume":"49","author":"Bae","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.taap.2012.06.021","article-title":"Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK\/p38 signaling and thromboxane A2 production","volume":"263","author":"Chang","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/BF03356451","article-title":"Protective effect of Dryopteris crassirhizoma extracts in the control of the root-knot nematode Meloidogyne incognita","volume":"120","author":"Liu","year":"2013","journal-title":"J. Plant Dis. Prot."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1155\/2013\/313482","article-title":"Effects of Chloroform Extract of Dryopteris crassirhizoma on the Ultramicroscopic Structures of Meloidogyne incognita","volume":"2013","author":"Liu","year":"2013","journal-title":"Sci. World J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1039\/b914364p","article-title":"Phloroglucinol compounds of natural origin: Synthetic aspects","volume":"27","author":"Singh","year":"2010","journal-title":"Nat. Prod. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.193.4.459","article-title":"Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice","volume":"193","author":"Nieswandt","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1182\/blood-2002-10-3242","article-title":"Targeting of the collagen-binding site on glycoprotein VI is not essential for in vivo depletion of the receptor","volume":"101","author":"Schulte","year":"2003","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0922-4106(95)90075-6","article-title":"Effect of berbamine on cytosolic phospholipase A2 activation in rabbit platelets","volume":"291","author":"Akiba","year":"1995","journal-title":"Eur. J. Pharmacol. Mol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0049-3848(98)00097-8","article-title":"Translocation and phosphorylation of cytosolic phospholipase A2 in activated platelets","volume":"92","author":"McNicol","year":"1998","journal-title":"Thromb. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0005-2760(87)90096-8","article-title":"Evidence for the release of arachidonic acid through the selective action of phospholipase A2 in thrombin-stimulated human platelets","volume":"920","author":"Purdon","year":"1987","journal-title":"Biochim. Et Biophys. Acta (Bba)-Lipids Lipid Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.atherosclerosis.2009.02.034","article-title":"Antithrombotic and antiplatelet activities of fenofibrate, a lipid-lowering drug","volume":"206","author":"Lee","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1113\/jphysiol.1963.sp007185","article-title":"The aggregation of blood platelets","volume":"168","author":"Born","year":"1963","journal-title":"J. Physiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/12\/2212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:58:04Z","timestamp":1760187484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/12\/2212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,13]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["molecules24122212"],"URL":"https:\/\/doi.org\/10.3390\/molecules24122212","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,13]]}}}