{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:19Z","timestamp":1787029039335,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Korea Bioactive Natural Material Bank","award":["NRF-2017M3A9B8069409"],"award-info":[{"award-number":["NRF-2017M3A9B8069409"]}]},{"name":"the Bio &amp; Technology Development","award":["NRF-2016M3A9A5919863"],"award-info":[{"award-number":["NRF-2016M3A9A5919863"]}]},{"name":"the KRIBB Research Initiative Program","award":["1234"],"award-info":[{"award-number":["1234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson\u2019s disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg\/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson\u2019s disease mouse model.<\/jats:p>","DOI":"10.3390\/molecules24071435","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T03:46:37Z","timestamp":1555040797000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dereplication of Components Coupled with HPLC-qTOF-MS in the Active Fraction of Humulus japonicus and It\u2019s Protective Effects against Parkinson\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Hee Ju","family":"Lee","sequence":"first","affiliation":[{"name":"Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea"},{"name":"Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung 25451, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basanta","family":"Dhodary","sequence":"additional","affiliation":[{"name":"Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Pyo","family":"An","sequence":"additional","affiliation":[{"name":"Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Kyoung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-8359","authenticated-orcid":false,"given":"Kyoung-Shim","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-5746","authenticated-orcid":false,"given":"Chul-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-3064","authenticated-orcid":false,"given":"Won Keun","family":"Oh","sequence":"additional","affiliation":[{"name":"Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0005-2728(98)00114-5","article-title":"Mitochondrial dysfunction in neurodegenerative diseases","volume":"1366","author":"Beal","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1212\/WNL.66.10_suppl_4.S24","article-title":"The pathogenesis of cell death in Parkinson\u2019s disease","volume":"66","author":"Jenner","year":"2006","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2174\/0929867053764635","article-title":"Metals, toxicity and oxidative stress","volume":"12","author":"Valko","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11745-999-0350-3","article-title":"Effects of dietary polyunsaturated fatty acids on neuronal function","volume":"34","author":"Fernstrom","year":"1999","journal-title":"Lipids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0006-8993(96)01056-6","article-title":"Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons","volume":"743","author":"Cheng","year":"1996","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.freeradbiomed.2007.04.028","article-title":"6-Hydroxydopamine induces mitochondrial ERK activation","volume":"43","author":"Kulich","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1074\/jbc.M112.421354","article-title":"Blocking c-Jun N-terminal kinase (JNK) translocation to the mitochondria prevents 6-hydroxydopamine-induced toxicity in vitro and in vivo","volume":"288","author":"Chambers","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_9","first-page":"1","article-title":"Molecular basis of human MAO A and B","volume":"4","author":"Shih","year":"1991","journal-title":"Neuropsychopharmacology"},{"key":"ref_10","first-page":"89","article-title":"Age-related changes on MAO in Bl\/C57 mouse tissues: A quantitative radioautographic study","volume":"41","author":"Saura","year":"1994","journal-title":"J. Neural. Transm. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/265080a0","article-title":"Dopamine is a monoamine oxidase B substrate in man","volume":"265","author":"Glover","year":"1977","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/mds.23795","article-title":"Neuropathology of sporadic Parkinson\u2019s disease: Evaluation and changes of concepts","volume":"27","author":"Jellinger","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuropharm.2012.08.023","article-title":"Selective inhibition of monoamine oxidase A or B reduces striatal oxidative stress in rats with partial depletion of the nigro-striatal dopaminergic pathway","volume":"65","author":"Aluf","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nrd2087","article-title":"Novel pharmacological targets for the treatment of Parkinson\u2019s disease","volume":"5","author":"Schapira","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1001\/jama.2014.3654","article-title":"Pharmacological treatment of Parkinson disease: A review","volume":"311","author":"Connolly","year":"2014","journal-title":"JAMA"},{"key":"ref_16","first-page":"464","article-title":"Antimicrobial and antioxidative activities of solvent fraction from Humulus japonicas","volume":"26","author":"Park","year":"1994","journal-title":"Korean J. Food Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1089\/jmf.2016.3851","article-title":"Humulus japonicus prevents dopaminergic neuron death in 6-hydroxydopamine-induced models of Parkinson\u2019s disease","volume":"20","author":"Ryu","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3892\/ijmm.2016.2804","article-title":"Humulus japonicus inhibits the progression of Alzheimer\u2019s disease in a APP\/PS1 transgenic mouse model","volume":"39","author":"Park","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1039\/C6NP00024J","article-title":"Modern mass spectrometry for synthetic biology and structure-based discovery of natural products","volume":"33","author":"Henke","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1080\/13880200308951345","article-title":"Three megastigmane glycosides from the leaves of Pterospermum semisagittaum","volume":"41","author":"Khan","year":"2003","journal-title":"Pharm. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/0031-9422(92)83121-E","article-title":"Two diastereomeric 3-oxo-alpha-ionol beta-D-glucosides from raspberry fruit","volume":"31","author":"Pabst","year":"1992","journal-title":"Phytochemisty"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19789","DOI":"10.3390\/molecules201119657","article-title":"Antihypertensive effects of Artemisia scoparia Waldst in spontaneously hypertensive rats and identification of angiotensin I converting enzyme inhibitors","volume":"20","author":"Cho","year":"2015","journal-title":"Molecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S0031-9422(98)00092-2","article-title":"Antialgal compounds from Zantedeschia aethiopica","volume":"49","author":"Greca","year":"1998","journal-title":"Phytochemisty"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s12272-012-0303-8","article-title":"A new flavonol glycoside from Hylomecon vernalis","volume":"35","author":"Lee","year":"2012","journal-title":"Arch. Pharm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1021\/np980436g","article-title":"Antioxidative phenolic glycosides from sage (Salvia officinalis)","volume":"62","author":"Wang","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1007\/BF02977373","article-title":"Two new phenolic constituents of Humulus japonicus and their cytotoxicity test in vitro","volume":"30","author":"Yu","year":"2007","journal-title":"Arch. Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/mrc.2054","article-title":"A predictive tool for assessing 13 C NMR chemical shifts of flavonoids","volume":"45","author":"Burns","year":"2007","journal-title":"Magn. Reson. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/BF02490811","article-title":"Quantitation of 8-prenylnaringenin, a novel phytoestrogen in Hops (Humulus lupulus L.), hop products, and beers, by benchtop HPLC-MS using electrospray ionization","volume":"51","author":"Rong","year":"2000","journal-title":"Chromatographia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1007\/s11306-011-0335-y","article-title":"Metabolite profiling and fingerprinting of commercial cultivars of Humulus lupulu L. (hop): A comparison of MS and NMR methods in metabolomics","volume":"8","author":"Mohamed","year":"2012","journal-title":"Metabolomics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1021\/jm070677y","article-title":"Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs","volume":"50","author":"Binda","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11744","DOI":"10.1523\/JNEUROSCI.0864-14.2014","article-title":"Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson\u2019s disease","volume":"34","author":"Park","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.phytochem.2017.02.007","article-title":"Neolignan and megastigmane glucosides from the aerial parts of Isodon japonicus with cell protective effects on BaP-induced cytotoxicity","volume":"137","author":"Matsumoto","year":"2017","journal-title":"Phytochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rezai-Zadeh, K., Ehrhart, J., Bai, Y., Sanberg, P.R., Bickford, P., Tan, J., and Shytle, R.D. (2008). Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J. Neuroinflamm., 5.","DOI":"10.1186\/1742-2094-5-41"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3390\/ijms15010895","article-title":"Luteolin reduces Alzheimer\u2019s disease pathologies induced by traumatic brain injury","volume":"15","author":"Sawmiller","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S0014-5793(00)01211-4","article-title":"Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase","volume":"468","author":"Day","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7700","DOI":"10.1021\/jf505848z","article-title":"Isolation of luteolin and luteolin-7-O-glucoside from Dendranthema morifolium Ramat Tzvel and their pharmacokinetics in rats","volume":"63","author":"Lin","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","first-page":"29","article-title":"Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans","volume":"2","author":"Plumb","year":"2003","journal-title":"Eur. J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3945\/jn.108.102814","article-title":"The bioavailability of apigenin-7-glucoside is influenced by human intestinal microbiota in rats","volume":"139","author":"Hanske","year":"2009","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.phymed.2008.12.021","article-title":"In vitro evaluation of antibacterial, anticollagenase, and antioxidant activities of hop components (Humulus lupulus) addressing acne vulgaris","volume":"16","author":"Naoto","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbr.2015.01.053","article-title":"A partial lesion model of Parkinson\u2019s disease in mice-- characterization of a 6-OHDA-induced medial forebrain bundle lesion","volume":"284","author":"Boix","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0160-5402(85)90021-X","article-title":"An improved fluorimetric assay for brain monoamine oxidase","volume":"13","author":"Morinan","year":"1985","journal-title":"J. Pharmacol. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/7\/1435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:44:43Z","timestamp":1760186683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/7\/1435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,11]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["molecules24071435"],"URL":"https:\/\/doi.org\/10.3390\/molecules24071435","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,11]]}}}