{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:18:03Z","timestamp":1783390683295,"version":"3.54.6"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The R&amp;D Convergence Program of the Republic of Korea National Research Council of Science and Technology","award":["CRC-15-04-KIST, KSN 1621850, NSN1522380"],"award-info":[{"award-number":["CRC-15-04-KIST, KSN 1621850, NSN1522380"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Mumefural is a bioactive compound derived from the processed fruit of Prunus mume Sieb. et Zucc., a traditional health food; however, its safety has not been evaluated. We investigated the toxicity of mumefural through single and repeated oral administration at doses of 1250, 2500, and 5000 mg\/kg in Institute of Cancer Research (ICR) mice. The acute toxicity assessment was not associated with adverse effects or death. Similarly, the subacute (four weeks) toxicity assessment did not reveal any mumefural-associated mortality, abnormal organ damage, or altered clinical signs, body weight, food consumption, or hematological parameters. However, albumin\/globulin ratio and chloride ion levels were significantly increased in male mice treated with mumefural at \u22652500 mg\/kg. Female mice exhibited significantly higher levels of chloride, sodium, and potassium ions, at a dose of 5000 mg\/kg. Furthermore, the administration of 2500 and 5000 mg\/kg mumefural decreased the absolute weight of spleen in male mice. These findings indicated that the approximate lethal dose of mumefural in ICR mice was &gt;5000 mg\/kg. No significant mumefural toxicity was observed at \u22645000 mg\/kg. Our findings provide a basis for conducting future detailed studies to evaluate reproductive, neurological, genetic, and chronic toxicity of mumefural.<\/jats:p>","DOI":"10.3390\/nu12051328","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T03:45:20Z","timestamp":1588909520000},"page":"1328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Acute and Subacute Oral Toxicity of Mumefural, Bioactive Compound Derived from Processed Fruit of Prunus mume Sieb. et Zucc., in ICR Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Jungim","family":"Kim","sequence":"first","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daejeon 34054, Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6638-5877","authenticated-orcid":false,"given":"Mira","family":"Han","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daejeon 34054, Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Kyung","family":"Jeon","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daejeon 34054, Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","unstructured":"Jung, B., and Shin, M. (1990). Encyclopedia of Illustrated Korean Natural Drugs, Young Lim Sa."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11504","DOI":"10.1038\/s41598-018-29701-2","article-title":"A Novel Compound, \u201cFA-1\u201d Isolated from Prunus mume, Protects Human Bronchial Epithelial Cells and Keratinocytes from Cigarette Smoke Extract-Induced Damage","volume":"8","author":"Jang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liu, Z.L. (2009). Essentials of Chinese Medicine, Springer.","DOI":"10.1007\/978-1-84882-596-3"},{"key":"ref_4","unstructured":"Christensen, M. (2016). A Systematic Review of Ume Health Benefits, St. Catherine University. 5-2016."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s12199-014-0404-8","article-title":"Safety and adherence of Umezu polyphenols in the Japanese plum (Prunus mume) in a 12-week double-blind randomized placebo-controlled pilot trial to evaluate antihypertensive effects","volume":"19","author":"Takemura","year":"2014","journal-title":"Environ. Health Prev. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ko, B.S., Kim, D.S., Kang, S., Ryuk, J.A., and Park, S. (2013). Prunus mume and Lithospermum erythrorhizon Extracts Synergistically Prevent Visceral Adiposity by Improving Energy Metabolism through Potentiating Hypothalamic Leptin and Insulin Signalling in Ovariectomized Rats. Evid.-Based Complementary Altern. Med. ECAM, 2013.","DOI":"10.1155\/2013\/750986"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"596","DOI":"10.4254\/wjh.v5.i10.596","article-title":"Advanced hepatocellular carcinoma responds to MK615, a compound extract from the Japanese apricot \u201cPrunus mume\u201d","volume":"5","author":"Hoshino","year":"2013","journal-title":"World J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/ptr.3645","article-title":"MK615, a Prunus mume Steb. Et Zucc (\u2018Ume\u2019) extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1\/2-Id-1 pathway","volume":"26","author":"Tada","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1002\/ptr.5597","article-title":"Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized, Double-Blind, Placebo-Controlled Study","volume":"30","author":"Beretta","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1467-2494.1997.tb00194.x","article-title":"Biological screening of 100 plant extracts for cosmetic use (II): Anti-oxidative activity and free radical scavenging activity","volume":"19","author":"Kim","year":"1997","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1089\/jmf.2015.3512","article-title":"Fructus mume Ethanol Extract Prevents Inflammation and Normalizes the Septohippocampal Cholinergic System in a Rat Model of Chronic Cerebral Hypoperfusion","volume":"19","author":"Kim","year":"2016","journal-title":"J. Med. Food"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lee, K.M., Bang, J., Kim, B.Y., Lee, I.S., Han, J.S., Hwang, B.Y., and Jeon, W.K. (2015). Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling. BMC Complementary Altern. Med., 15.","DOI":"10.1186\/s12906-015-0652-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1248\/bpb.b17-00711","article-title":"Antimicrobial Activity of the Phenolic Compounds of Prunus mume against Enterobacteria","volume":"41","author":"Mitani","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Park, J.C., Ma, J., Jeon, W.K., and Han, J.S. (2016). Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice. BMC Complementary Altern. Med., 16.","DOI":"10.1186\/s12906-016-1414-4"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kim, M.S., Jeon, W.K., Lee, K.W., Park, Y.H., and Han, J.S. (2015). Ameliorating Effects of Ethanol Extract of Fructus mume on Scopolamine-Induced Memory Impairment in Mice. Evid.-Based Complementary Altern. Med. ECAM, 2015.","DOI":"10.1155\/2015\/102734"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1021\/jf980960t","article-title":"Mumefural, citric acid derivative improving blood fluidity from fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc)","volume":"47","author":"Chuda","year":"1999","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","unstructured":"(2020, March 26). Showing Metabocard for Mumefural (HMDB0035179). Available online: https:\/\/hmdb.ca\/metabolites\/HMDB0035179."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1080\/08927022.2011.577074","article-title":"Treat Alzheimer\u2019s disease by traditional Chinese medicine?","volume":"37","author":"Sun","year":"2011","journal-title":"Mol. Simul."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1080\/07391102.2013.790849","article-title":"Discovery of novel insomnia leads from screening traditional Chinese medicine database","volume":"32","author":"Chen","year":"2014","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.foodchem.2010.12.031","article-title":"Mumefural and related HMF derivatives from Japanese apricot fruit juice concentrate show multiple inhibitory effects on pandemic influenza A (H1N1) virus","volume":"127","author":"Sriwilaijaroen","year":"2011","journal-title":"Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bang, J., Kim, M.S., and Jeon, W.K. (2019). Mumefural Ameliorates Cognitive Impairment in Chronic Cerebral Hypoperfusion via Regulating the Septohippocampal Cholinergic System and Neuroinflammation. Nutrients, 11.","DOI":"10.3390\/nu11112755"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7638","DOI":"10.1016\/j.tet.2016.10.026","article-title":"Practical synthesis of mumefural, a component of Japanese apricot juice concentrate","volume":"72","author":"Sugimura","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3136\/nskkk.50.188","article-title":"Quantitative analysis method for mumefural in Japanese apricot fruit [Prunus mume] juice concentrate","volume":"50","author":"Yada","year":"2003","journal-title":"J. Jpn. Soc. Food Sci. Technol. (Jpn.)"},{"key":"ref_24","first-page":"5","article-title":"Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and its Implementation in Japan","volume":"65","author":"Muneyuki","year":"2010","journal-title":"Natl. Inst. Occup. Saf. Health"},{"key":"ref_25","first-page":"17","article-title":"Stress produced by gavage administration in the rat","volume":"39","author":"Brown","year":"2000","journal-title":"Contemp. Top. Lab. Anim. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/laban0512-129","article-title":"The effects of repeated oral gavage on the health of male CD-1 mice","volume":"41","author":"Henriques","year":"2012","journal-title":"Lab Anim. (N. Y.)"},{"key":"ref_27","first-page":"37","article-title":"Simultaneous determination and acute toxicity study of Fructus mume extracts in ICR mice","volume":"15","author":"Lee","year":"2011","journal-title":"J. Soc. Prev. Korean Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"873","DOI":"10.31989\/ffhd.v7i11.394","article-title":"Effects and safety of daily ingestion of plum extract on blood pressure:randomized, double-blinded, placebo-controlled parallel group comparison study","volume":"7","author":"Nishimura","year":"2017","journal-title":"Funct. Foods Health Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Middendorf, P.J., and Williams, P.L. (2000). Nephrotoxicity: Toxic responses of the kidney. Princ. Toxicol. Environ. Ind. Appl., 129\u2013143.","DOI":"10.1002\/0471231800.ch6"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. Rev. Immunol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/5\/1328\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:26:21Z","timestamp":1760174781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/5\/1328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,7]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["nu12051328"],"URL":"https:\/\/doi.org\/10.3390\/nu12051328","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,7]]}}}