{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:27:19Z","timestamp":1790998039141,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"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>Ethnobotanical field surveys revealed the use of fruits of Opuntia ficus indica (L.) Mill. for treating diabetes, burns, bronchial asthma, constipation, kidney stones, and rheumatic pains and as a sedative in Turkish folk medicine. This study aimed to verify the efficacy of the fruits of O. ficus indica experimentally and to define components responsible for the activity using bioassay-guided procedures. The crude methanolic extract of the fruits was sequentially fractionated into five subextracts: n-hexane, dichloromethane, ethyl acetate, n-butanol, and water. Further experiments were carried out on the most active subextract, that is, the ethyl acetate (EtOAc) subextract, which was further subjected to fractionation through successive column chromatographic applications on Sephadex LH-20. For activity assessment, each extract or fraction was submitted to bioassay systems; traction test, fireplace test, hole-board test, elevated plus-maze test, and open-field test were used for sedative and anxiolytic effects, and a thiopental-induced sleeping test was used for the hypnotic effect. Among the subextracts obtained from the methanolic extract, the EtOAc subextract showed significant sedative and anxiolytic effects in the bioassay systems. From the EtOAc subextract, major components were isolated, and their structures were determined as isorhamnetin, isorhamnetin 3-O-glucoside, isorhamnetin 3-O-rutinoside, and kaempferol 3-O-rutinoside using spectral techniques. In conclusion, this study confirmed the claimed use of the plant against anxiety in Turkish folk medicine.<\/jats:p>","DOI":"10.3390\/molecules25081844","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:48:52Z","timestamp":1587448132000},"page":"1844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Sedative and Anxiolytic Activities of Opuntia ficus indica (L.) Mill.: An Experimental Assessment in Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-7869","authenticated-orcid":false,"given":"Esra K\u00fcpeli","family":"Akkol","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, Ankara 06330, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mert","family":"Ilhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University, Tu\u015fba 65080, Van, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00fc\u015fra","family":"Karpuz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, Ankara 06330, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Gen\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, S\u0131hhiye, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-2544","authenticated-orcid":false,"given":"Eduardo","family":"Sobarzo-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, 8330507 Santiago, Chile"},{"name":"Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.euroneuro.2005.04.010","article-title":"The epidemiology of generalized anxiety disorder in Europe","volume":"15","author":"Lieb","year":"2005","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_2","unstructured":"Katzung, B.G., Masters, S.B., and Trevor, A.J. (2009). Basic and Clinical Pharmacology, McGraw-Hill. [11th ed.]."},{"key":"ref_3","first-page":"151","article-title":"Benzodiazepines: Use, abuse, and consequences","volume":"44","author":"Woods","year":"1992","journal-title":"Pharmacol. Rev."},{"key":"ref_4","first-page":"215","article-title":"Attenuation of benzodiazepine dependence in mice by a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: A non-habit forming anxiolytic","volume":"6","author":"Dhawan","year":"2003","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_5","first-page":"22","article-title":"Changes in physical properties and chemical composition of cactus pear (Opuntia ficus-indica) during maturation","volume":"7","author":"Duru","year":"2005","journal-title":"J. Prof. Assoc. Cactus"},{"key":"ref_6","first-page":"540","article-title":"Antihyperglycemic activity of prickly pear (Opuntia ficus-indica) aqueous extract","volume":"2","author":"Halmi","year":"2012","journal-title":"IJMAP"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-8741(01)00196-9","article-title":"Antiulcer activity of Opuntia ficus indica (L.) Mill. (Cactaceae): Ultrastructural study","volume":"76","author":"Galati","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rodriguez-Felix, A. (2000). Postharvest physiology and technology of cactus pear fruits and cactus leaves. Acta Hortic., 191\u2013199.","DOI":"10.17660\/ActaHortic.2002.581.18"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/BF02859062","article-title":"The prickly-pears (Opuntia spp., Cactaceae)\u2014A source of human and animal food in semiarid regions","volume":"41","author":"Russell","year":"1987","journal-title":"Econ. Bot."},{"key":"ref_10","first-page":"21","article-title":"Cacti (Opuntia spp.) as a fodder crop for marginal lands in the Mediterranean basin","volume":"581","year":"2002","journal-title":"Acta Hortic."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/089030600263058","article-title":"Utilization of fodder trees and shrubs in the arid and semiarid zones of West Asia and North Africa","volume":"14","year":"2000","journal-title":"Arid Soil Res. Rehab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0140-1963(18)30574-3","article-title":"Crude protein and phosphorus contents of eight contrasting Opuntia forage clones","volume":"22","author":"Gregory","year":"1992","journal-title":"J. Arid Environ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1006\/fstl.2001.0787","article-title":"Modified atmosphere packaging of prickly pear cactus stems (Opuntia spp.)","volume":"34","author":"Guevara","year":"2001","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/jare.1997.0261","article-title":"Fruit quality and production of cactus pear (Opuntia spp.) fruit clones selected for increased frost hardiness","volume":"37","author":"Parish","year":"1997","journal-title":"J. Arid Environ."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1016\/j.foodres.2011.02.042","article-title":"Nutr.itional components and anti-oxidant capacity of ten cultivars and lines of cactus pear fruit (Opuntia spp.)","volume":"44","author":"Yahia","year":"2011","journal-title":"Food Res. Int."},{"key":"ref_16","first-page":"136","article-title":"Some functional, chemical, and sensory characteristics of cactus pear rice-based extrudates","volume":"9","author":"Habiba","year":"2007","journal-title":"J. Prof. Assoc. Cactus"},{"key":"ref_17","first-page":"1","article-title":"Producing ice cream with concentrated cactus pear pulp: A preliminary study","volume":"11","author":"Youssef","year":"2009","journal-title":"J. Prof. Assoc. Cactus"},{"key":"ref_18","first-page":"1","article-title":"Cactus pear fruits (Opuntia spp.): A review of processing technologies and current uses","volume":"8","author":"Stintzing","year":"2006","journal-title":"J. Prof. Assoc. Cactus"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jep.2005.09.017","article-title":"Opuntia ficus-indica attenuates neuronal injury in in vitro and in vivo models of cerebral ischemia","volume":"104","author":"Kim","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jep.2012.12.012","article-title":"An ethnobotanical study of medicinal plants in Marmaris (Mugla, Turkey)","volume":"146","author":"Gurdal","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1016\/j.foodres.2011.02.011","article-title":"Phenolics, betacyanins and antioxidant activity in Opuntia joconostle fruits","volume":"44","author":"Alvarez","year":"2011","journal-title":"Food Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1023\/A:1008000232406","article-title":"Composition of pulp, skin and seeds of prickly pears fruit (Opuntia ficus indica sp.)","volume":"52","author":"Villaume","year":"1998","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14879","DOI":"10.3390\/molecules190914879","article-title":"Nopal cactus (Opuntia ficus-indica) as a source of bioactive compounds for Nutr.ition, health and disease","volume":"19","author":"Badreddine","year":"2014","journal-title":"Molecules"},{"key":"ref_24","first-page":"11","article-title":"Chemical composition and functional properties of prickly pear (Opuntia ficus indica) seeds flour and protein concentrate","volume":"3","author":"Nassar","year":"2008","journal-title":"World J. Dairy Food Sci."},{"key":"ref_25","first-page":"9","article-title":"Cactus pear: A fruit of Nutraceutical and functional importance","volume":"6","author":"Piga","year":"2004","journal-title":"J. Prof. Assoc. Cactus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0308-8146(02)00550-2","article-title":"Oil cactus pear (Opuntia ficus-indica L.)","volume":"82","author":"Ramadan","year":"2003","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1007\/s002170000219","article-title":"Phytochemical and Nutr.itional significance of cactus pear","volume":"212","author":"StIntzing","year":"2001","journal-title":"Eur. Food Res. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1590\/S0100-879X1998000600005","article-title":"Isolation and characterization of a reserve protein from the seeds of Opuntia ficus-indica (Cactaceae)","volume":"31","author":"Uchoa","year":"1998","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0308-8146(03)00184-5","article-title":"Antioxidant compounds from four Opuntia cactus pear fruit varieties","volume":"85","author":"Kuti","year":"2004","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/S0031-9422(00)88524-6","article-title":"Biosynthesis of indicaxanthin in Opuntia ficus-indica fruits","volume":"11","author":"Impellizzeri","year":"1972","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1021\/jf011305f","article-title":"Identification of betalains from yellow beet (Beta vulgaris L.) and cactus pear [Opuntia ficus-indica (L.) Mill.] by high-performance liquid chromatography-electrospray ionization mass spectrometry","volume":"50","author":"StIntzing","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0308-8146(01)00196-0","article-title":"The stability of pelargonidin-based anthocyanins at varying water activity","volume":"75","author":"Wrolstad","year":"2001","journal-title":"Food Chem."},{"key":"ref_33","first-page":"1","article-title":"Kan portakal\u0131 suyunun baz\u0131 kalite parametreleri \u00fczerine \u0131\u015f\u0131k, pH, depolama, s\u0131cakl\u0131k ve s\u00fcresinin etkisi","volume":"8","author":"Toker","year":"2013","journal-title":"G\u0131da Teknol. Elektron. Derg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0378-8741(01)00337-3","article-title":"Biological effect of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. Note I: Diuretic activity","volume":"79","author":"Galati","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0378-8741(99)00027-6","article-title":"Preliminary studies of analgesic and anti-inflammatory properties of Opuntia dillenii aqueous extract","volume":"67","author":"Loro","year":"1999","journal-title":"J. Ethnopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0367-326X(00)00287-2","article-title":"An anti-inflammatory principle from cactus","volume":"72","author":"Park","year":"2001","journal-title":"Fitoterapia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0378-8741(02)00243-X","article-title":"Study on the increment of the production of gastric mucus in rats treated with Opuntia ficus indica (L.) Mill. cladodes","volume":"83","author":"Galati","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF02975264","article-title":"Effects of Opuntia ficus-indica var. saboten stem on gastric damages in rats","volume":"25","author":"Lee","year":"2002","journal-title":"Arch. Pharm. Res."},{"key":"ref_39","first-page":"316","article-title":"Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats","volume":"48","year":"1998","journal-title":"Arch. Latinoam. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/ptr.2650040507","article-title":"Hypoglycemic effect of Opuntia-ficus-indica in non-insulin-dependent diabetes-mellitus patients","volume":"4","author":"Frati","year":"1990","journal-title":"Phytother. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1080\/10826070802603369","article-title":"Preparative isolation of isorhamnetin from Stigma Maydis using high-speed countercurrent chromatography","volume":"32","author":"Cao","year":"2009","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112100","DOI":"10.1016\/j.jep.2019.112100","article-title":"Bioactivity-guided isolation of flavonoids from Urtica dioica L. and their effect on endometriosis rat model","volume":"243","author":"Ilhan","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"873954","DOI":"10.1155\/2015\/873954","article-title":"Evaluation of sedative and hypnotic activity of ethanolic extract of Scoparia dulcis Linn","volume":"2015","author":"Moniruzzaman","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0014-2999(98)00223-4","article-title":"Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and\/or anxiolytic state in mice","volume":"350","author":"Takeda","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1055\/s-2006-958058","article-title":"Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects","volume":"61","author":"Viola","year":"1995","journal-title":"Planta Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11418-012-0636-0","article-title":"Evaluation of n-hexane extract of Viola betonicifolia for its neuropharmacological properties","volume":"67","author":"Muhammad","year":"2013","journal-title":"J. Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bbr.2004.01.004","article-title":"Aged neuropeptide Y transgenic rats are resistant to acute stress but maInt.ain spatial and non-spatial learning","volume":"153","author":"Carvajal","year":"2004","journal-title":"Behav. Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0031-9384(01)00627-8","article-title":"Spatial memory deficit and emotional abnormality in OLETF rats","volume":"75","author":"Li","year":"2002","journal-title":"Physiol. Behav."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-4328(03)00112-8","article-title":"Spatial learning in male mice with different levels of aggressiveness: Effects of housing conditions and nicotine administration","volume":"147","author":"Moragrega","year":"2003","journal-title":"Behav. Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0166-4328(02)00273-5","article-title":"Persistent behavioral and autonomic supersensitivity to stress following prenatal stress exposure in rats","volume":"140","author":"Rimondini","year":"2003","journal-title":"Behav. Brain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.neulet.2003.12.005","article-title":"Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze","volume":"361","author":"Alcalay","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.neuropharm.2004.05.008","article-title":"Reduced anxiety and depression-like behavior in synaptotagmin IV (\u2212\/\u2212) mice","volume":"47","author":"Ferguson","year":"2004","journal-title":"Neuropharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1590\/S0100-879X1997000300002","article-title":"Animal models of anxiety: An ethological perspective","volume":"30","author":"Rodgers","year":"1997","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0014-2999(03)01272-X","article-title":"The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review","volume":"463","author":"Prut","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/j.1749-6632.1969.tb12982.x","article-title":"The open field: Some comparative data","volume":"159","author":"Candland","year":"1969","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbr.2003.08.002","article-title":"Acute tryptophan depletion induced by a gelatin-based mixture impairs object memory but not affective behavior and spatial learning in the rat","volume":"151","author":"Lieben","year":"2004","journal-title":"Behav. Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Islam, N.U., Khan, I., Rauf, A., Muhammad, N., Shahid, M., and Shah, M.R. (2015). Antinociceptive, muscle relaxant and sedative activities of gold nanoparticles generated by methanolic extract of Euphorbia milii. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0691-7"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/jnr.490070105","article-title":"Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors: A study with muSci.mol","volume":"7","author":"Sivam","year":"1982","journal-title":"J. Neurosci. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1113\/jphysiol.2001.012818","article-title":"Modulation of GABAA receptor channel gating by pentobarbital","volume":"537","author":"Steinbach","year":"2001","journal-title":"J. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jep.2009.06.034","article-title":"Ethnopharmacology of Q\u2019eqchi\u2019 Maya antiepileptic and anxiolytic plants: Effects on the GABAergic system","volume":"125","author":"Awad","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3109\/13880200903046153","article-title":"Anxiolytic-like and sedative actions of Rollinia mucosa: Possible involvement of the GABA\/benzodiazepine receptor complex","volume":"48","author":"Rocha","year":"2010","journal-title":"Pharm. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.pbb.2003.12.003","article-title":"Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis","volume":"77","author":"Fernandez","year":"2004","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1021\/jm020839k","article-title":"Refinement and evaluation of a pharmacophore model for flavone derivatives binding to the benzodiazepine site of the GABA(A) receptor","volume":"45","author":"Kahnberg","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.phrs.2004.08.007","article-title":"St John\u2019s wort (Hypericum perforatum) diminishes cognitive impairment caused by the chronic restraint stress in rats","volume":"51","author":"Trofimiuk","year":"2005","journal-title":"Pharmacol. Res."},{"key":"ref_65","first-page":"181","article-title":"Hypnotic effect of Rosa damascena in mice","volume":"3","author":"Rakhshandah","year":"2004","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejphar.2013.04.003","article-title":"Involvement of the GABAergic system in the anxiolytic-like effect of the flavonoid ellagic acid in mice","volume":"710","author":"Girish","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1023\/A:1027303609517","article-title":"Overview\u2014Flavonoids: A new family of benzodiazepine receptor ligands","volume":"22","author":"Medina","year":"1997","journal-title":"Neurochem. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jep.2015.01.029","article-title":"Interactions of a standardized flavonoid fraction from Tilia americana with serotoninergic drugs in elevated plus maze","volume":"164","author":"Zamilpa","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1016\/0024-3205(87)90758-2","article-title":"Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action","volume":"40","author":"Shephard","year":"1987","journal-title":"Life Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"37","DOI":"10.17711\/SM.0185-3325.2015.066","article-title":"Anxiolytic and sedative-like effects of flavonoids from Tilia americana var. mexicana: GABAergic and serotonergic participation","volume":"39","author":"Terrazas","year":"2016","journal-title":"Salud Ment."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.nano.2007.12.001","article-title":"Anxiety and cognitive effects of quercetin liposomes in rats","volume":"4","author":"Priprem","year":"2008","journal-title":"Nanomedicine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0091-3057(97)00054-3","article-title":"Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats","volume":"58","author":"Salgueiro","year":"1997","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S1360-1385(97)01018-2","article-title":"Antioxidant properties of phenolic compounds","volume":"2","author":"Miller","year":"1997","journal-title":"Trends Plant Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0006-8993(02)04150-1","article-title":"Neuroprotective effects of antioxidative flavonoids, quercetin, (+)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. saboten","volume":"965","author":"Lee","year":"2003","journal-title":"Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1248\/bpb.26.544","article-title":"Quercetin attenuates oxygen\u2013glucose deprivation-and excitotoxin-induced neurotoxicity in primary cortical cell cultures","volume":"26","author":"Ha","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s00702-010-0537-x","article-title":"Dietary inhibitors of monoamine oxidase A","volume":"118","author":"Clarke","year":"2011","journal-title":"J. Neural. Transm."},{"key":"ref_77","first-page":"130","article-title":"Isorhamnetin (IRN) attenuates cognitive dysfunction induced by the Int.racerebroventricular injection of amyloid beta 25\u201335 (A\u03b2 25\u201335) in Sprague Dawley rats","volume":"7","author":"Asha","year":"2015","journal-title":"J. Pharm. Sci. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jep.2006.04.024","article-title":"Nicotiflorin reduces cerebral ischemic damage and upregulates endothelial nitric oxide synthase in primarily cultured rat cerebral blood vessel endothelial cells","volume":"107","author":"Li","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_79","first-page":"1784","article-title":"Neuroprotective effects of flavonoids on hypoxia-, glutamate-, and oxidative stress-induced retinal ganglion cell death","volume":"17","author":"Nakayama","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.pbb.2007.03.003","article-title":"Protective effects of nicotiflorin on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats","volume":"86","author":"Huang","year":"2007","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_81","unstructured":"Courvoisier, S., Ducrot, R., and Julou, L. (1957). Psychotropic Drugs, Elsevier."},{"key":"ref_82","unstructured":"Laroche, M.J., and Rousselet, F. (1990). Les Animaux de Laboratoire: \u00c9thique et Bonnes Pratiques, Masson."},{"key":"ref_83","unstructured":"Hoffmann, G. (1963). Les Animaux de Laboratoire: Pr\u00e9cis, Vigot Freres."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF00404370","article-title":"Exploratory behavior in chronic disulfoton poisoning in mice","volume":"20","author":"Clark","year":"1971","journal-title":"Psychopharmacologia"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/BF00421184","article-title":"Validity of head-dipping as a measure of exploration in a modified hole-board","volume":"44","author":"File","year":"1975","journal-title":"Psychopharmacologia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jep.2004.06.022","article-title":"Coriandrum sativum: Evaluation of its anxiolytic effect in the elevated plus-maze","volume":"96","author":"Emamghoreishi","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jep.2005.12.006","article-title":"Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on isolated rat hearts and conscious mice","volume":"106","author":"Consolini","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8","DOI":"10.31254\/phyto.2013.2402","article-title":"Pharmacological evaluation of sedative and hypnotic activities of methanolic extract of Lycopus europaeus in mice","volume":"2","author":"Aziz","year":"2013","journal-title":"J. Phytopharm."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jep.2007.03.004","article-title":"Central nervous system depressant activity of an ethyl acetate extract from Ipomoea stans roots","volume":"112","author":"Gutierrez","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_90","unstructured":"Williamson, E.M., Okpako, D.T., and Evans, F.J. (1996). Selection, Preparation and Pharmacological Evaluation of Plant Material, John Wiley & Sons."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/8\/1844\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:21:17Z","timestamp":1760361677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/8\/1844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":90,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["molecules25081844"],"URL":"https:\/\/doi.org\/10.3390\/molecules25081844","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]}}}