{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:20:50Z","timestamp":1792844450328,"version":"4.5.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The World Health Organization reports that 30% of adults worldwide suffer from insomnia, while 10% of people worldwide suffer with various forms of anxiety. The significant negative effects of conventional medications used to treat anxiety and insomnia, such as abuse, addiction, amnesia, and cognitive and sexual dysfunction, have led to an increased preference for naturally derived substances with fewer side effects. Accordingly, in this study, the sedative and anxiolytic effects of <jats:italic>n<\/jats:italic>-hexane, ethyl acetate (EtOAc), methanol (MeOH) and water extracts of the aerial parts of <jats:italic>Capparis sicula<\/jats:italic> Duhamel., which is used for sedative purposes in folk medicine, were evaluated. To evaluate the sedative and anxiolytic effects of each extract, bioassay systems were used including traction and hole-board tests. The MeOH extract of <jats:italic>C. sicula<\/jats:italic> was the most active extract on <jats:italic>in vivo<\/jats:italic> traction and hole-board tests compared to Diazepam. From the MeOH extract, major components were isolated, and their structures were identified as three flavonoid glycosides [rutin (1), quercetin-3-<jats:italic>O<\/jats:italic>-glucoside (2), and quercetin 3-<jats:italic>O<\/jats:italic>-rhamnoside (3)] using spectral techniques. The most abundant component was determined to be rutin, comprising 8\u00a0mg\/100\u00a0mg dry extract in MeOH extract and 76.7\u00a0mg\/100\u00a0mg dry fraction in fraction C using HPLC. The molecular docking studies evaluated the interaction of isolated flavonoid glycosides with the interaction energies and protein-ligand interaction details of the anxiety-related receptors GABAA and GABAB. For the GABAA receptor, quercetin-3-<jats:italic>O<\/jats:italic>-glucoside demonstrated the highest docking score. Quercetin-3-<jats:italic>O<\/jats:italic>-rhamnoside and rutin also show promising interactions, particularly with the GABAB receptor, highlighting their potential as modulators of these receptors. In conclusion, the use of <jats:italic>C. sicula<\/jats:italic> for sedative purposes in folk medicine has been confirmed for the first time by <jats:italic>in vivo<\/jats:italic> studies, and its possible active compounds and sedative-anxiolytic mechanism have been determined through phytochemical and <jats:italic>in silico<\/jats:italic> studies.<\/jats:p>","DOI":"10.3389\/fphar.2024.1443173","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T04:32:17Z","timestamp":1724819537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Sedative and anxiolytic effects of Capparis sicula Duhamel: in vivo and in silico approaches with phytochemical profiling"],"prefix":"10.3389","volume":"15","author":[{"given":"B\u00fc\u015fra","family":"Karpuz A\u011f\u00f6ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"K\u00fcpeli Akkol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"\u00c7elik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Sobarzo-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.22037\/ijpr.2010.734","article-title":"Hepatoprotective activity of Capparis spinosa root bark against CCl4 induced hepatic damage in mice","volume":"6","author":"Aghel","year":"2010","journal-title":"Iran. J. Pharm. Res."},{"key":"B2","doi-asserted-by":"publisher","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":"Aguirre-Hern\u00e1ndez","year":"2016","journal-title":"Salud Ment."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3109\/13880201003629323","article-title":"Antinociceptive effect of methanol extract of Capparis ovata in mice","volume":"48","author":"Arslan","year":"2010","journal-title":"Pharm. Biol."},{"key":"B4","first-page":"123","article-title":"Capparis ovata desf. Farelerde karaci\u011fer enzimleri ile baz\u0131 kan parametreleri \u00fczerine etkisi","volume":"9","author":"Ba\u011fc\u0131","year":"1999","journal-title":"Genel T\u0131p Derg."},{"key":"B5","article-title":"T\u00fcrkiye\u2019de Bitkiler ile Tedavi, Ge\u00e7miste ve Bug\u00fcn Therapy with Medicinal Plants in Turkey","volume-title":"Past and present","author":"Baytop","year":"1999"},{"key":"B6","article-title":"Fleurs du Sahara","volume-title":"Voyageethnobota-nique avec les Touaregs du Tassili","author":"Benehelah","year":"2000"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1021\/np040106y","article-title":"The role of natural product chemistry in drug discovery","volume":"67","author":"Butler","year":"2004","journal-title":"J. Nat. Prod."},{"key":"B8","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/s0031-9422(01)00399-5","article-title":"6S-Hydroxy- 3-oxo-a-ionol glucosides from Capparis spinosa fruits","volume":"59","author":"Calis","year":"2002","journal-title":"Phytochem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/jcb.30226","article-title":"A computational comparative analysis of the binding mechanism of molnupiravir's active metabolite to RNA-dependent RNA polymerase of wild-type and Delta subvariant AY. 4 of SARS-CoV-2","volume":"123","author":"Celik","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"B10","first-page":"481","article-title":"Effect of Capparis decidua on hypolipidemic activity in rats","volume":"3","author":"Chahlia","year":"2009","journal-title":"J. Med. Plant. Res."},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.biopha.2018.12.114","article-title":"Anticonvulsant, sedative, anxiolytic and antidepressant activities of the essential oil of Annona vepretorum in mice: involvement of GABAergic and serotonergic systems","volume":"11","author":"Coimbra Diniz","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"B13","volume-title":"Psychotropic drugs","author":"Courvoisier","year":"1957"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1002\/jsfa.7040","article-title":"Physicochemical properties of caper species seed oils collected from two different harvest years","volume":"95","author":"Duman","year":"2015","journal-title":"J. Sci. Food Agric."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2","DOI":"10.4172\/2155-9864.1000142","article-title":"The antioxidant effects of Cappar\u0131s ovata and deferasirox in patients with thalassemia major","volume":"4","author":"Duman","year":"2013","journal-title":"J. Blood Disord. Transf."},{"key":"B16","article-title":"The pharmacology of anxiety","volume-title":"Behavioral neurobiology of anxiety and its treatment, current topics in behavioral neurosciences","author":"Durant","year":"2010"},{"key":"B17","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12906-017-1569-7","article-title":"Anti-inflammatory potential of Capparis spinosa L. in vivo in mice through inhibition of cell infiltration and cytokine gene expression","volume":"17","author":"El Azhary","year":"2017","journal-title":"BMC Complement. Altern. Med."},{"key":"B18","first-page":"52","article-title":"Ge\u00e7mi\u015ften g\u00fcn\u00fcm\u00fcze t\u0131bbi ve aromatik bitkilerin kullan\u0131lmas\u0131 ve ekonomik \u00f6nemi","volume":"11","author":"Faydao\u011flu","year":"2011","journal-title":"J. For."},{"key":"B19","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ejphar.2006.04.004","article-title":"Central nervous system depressant action of flavonoid glycosides","volume":"539","author":"Fern\u00e1ndez","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-386454-3.00241-4","article-title":"Anxiolytics","volume-title":"Encyclopedia of toxicology","author":"Fuentes","year":"2014"},{"key":"B22","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.biopha.2018.02.002","article-title":"The sedative activity of flavonoids from Passiflora quadrangularis is mediated through the GABAergic pathway","volume":"100","author":"Gazola","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B23","doi-asserted-by":"publisher","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":"B24","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s11418-009-0339-3","article-title":"Sedative and anticonvulsant effects of an alcoholic extract of Capparis decidua","volume":"63","author":"Goyal","year":"2009","journal-title":"J. Nat. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.indcrop.2014.12.059","article-title":"Capparis species: a potential source of bioactives and high-value components: a review","volume":"67","author":"Gull","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"B26","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1071\/ch22108","article-title":"Natural products isolation studies of native Australian fern species","volume":"75","author":"Gyeltshen","year":"2022","journal-title":"Aust. J. Chem."},{"key":"B27","volume-title":"ICH guideline Q2(R2)","year":"2022"},{"key":"B28","year":"2023","journal-title":"Glob. Health Data Exch. (GHDx)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1055\/s-0034-1376963","article-title":"Antidepressant and anxiolytic effects of the methanol root extract of Capparis thonningii: involvement of monoaminergic, cholinergic and GABAergic systems","volume":"65","author":"Ishola","year":"2015","journal-title":"Drug Res. (Stuttg)."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7149","DOI":"10.3390\/molecules27217149","article-title":"Anxiolytic-like effect of quercetin possibly through GABA receptor interaction pathway: in vivo and in silico studies","volume":"27","author":"Islam","year":"2022","journal-title":"Molecules"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.3390\/molecules16021471","article-title":"Flavonoids and the CNS","volume":"16","author":"J\u00e4ger","year":"2011","journal-title":"Molecules"},{"key":"B32","volume-title":"Basic and clinical pharmacology","author":"Katzung","year":"2018"},{"key":"B33","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.jep.2015.11.035","article-title":"Anxiolytic and sedative activities of aqueous leaf extract of Dichrocephala integrifolia (Asteraceae) in mice","volume":"176","author":"Ketcha Wanda","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"9539","DOI":"10.1038\/s41598-023-36540-3","article-title":"Forecasting of potential anti-inflammatory targets of some immunomodulatory plants and their constituents using in vitro, molecular docking and network pharmacology-based analysis","volume":"13","author":"Khairy","year":"2023","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22037\/ipa.v4i1.34526","article-title":"Sedative-hypnotic effects of different extracts and fractions of Capparis spinosa L","volume":"4","author":"Khoramjouy","year":"2021","journal-title":"Mice. IPA."},{"key":"B36","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41586-020-2654-5","article-title":"Shared structural mechanisms of general anaesthetics and benzodiazepines","volume":"585","author":"Kim","year":"2020","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.3390\/molecules25081844","article-title":"Sedative and anxiolytic activities of Opuntia ficus indica (L.) Mill.: an experimental assessment in mice","volume":"25","author":"K\u00fcpeli Akkol","year":"2020","journal-title":"Molecules"},{"key":"B38","volume-title":"Les animaux de laboratoire: \u00b4ethique et bonnes pratiques","author":"Laroche","year":"1990"},{"key":"B39","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3389\/fphar.2013.00092","article-title":"Traditional medicines and globalization: current and future perspectives in ethnopharmacology","volume":"4","author":"Leonti","year":"2013","journal-title":"Front. Pharmacol."},{"key":"B40","doi-asserted-by":"publisher","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":"B41","doi-asserted-by":"publisher","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":"B42","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1007\/s11064-013-0978-3","article-title":"Capparis ovata modulates brain oxidative toxicity and epileptic seizures in pentylentetrazol-induced epileptic rats","volume":"38","author":"Naz\u0131ro\u011flu","year":"2013","journal-title":"Neurochem. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.bbalip.2015.02.008","article-title":"Physiological feedback regulation of cholesterol biosynthesis: role of translational control of hepatic HMG-CoA reductase and possible involvement of oxylanosterols","volume":"1851","author":"Ness","year":"2015","journal-title":"Biochim. Biophys. Acta."},{"key":"B44","doi-asserted-by":"publisher","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":"Noguer\u00f3n-Merino","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"568","DOI":"10.4314\/ajtcam.v10i6.32","article-title":"Sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis in mice","volume":"10","author":"Olayiwola","year":"2013","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"241","DOI":"10.24190\/issn2564-615x\/2017\/03.08","article-title":"A potential therapeutic role in multiple sclerosis for stigmast-5,22-dien-3\u03b2-ol myristate isolated from Capparis ovata","volume":"1","author":"Ozgun-Acar","year":"2017","journal-title":"Eurobiotech J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.jep.2005.06.006","article-title":"Ethnopharmacology and drug discovery","volume":"100","author":"Patwardhan","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4060","DOI":"10.3390\/molecules27134060","article-title":"From traditional ethnopharmacology to modern natural drug discovery: a methodology discussion and specific examples","volume":"27","author":"Pirintsos","year":"2022","journal-title":"Molecules"},{"key":"B49","doi-asserted-by":"publisher","first-page":"10","DOI":"10.5138\/ijpm.v2i1.80","article-title":"Phytochemical and pharmacological potential of kair (Capparis decidua)","volume":"2","author":"Rathee","year":"2011","journal-title":"Int. J. Phytomed."},{"key":"B50","doi-asserted-by":"publisher","first-page":"47","DOI":"10.33393\/dti.2024.2745","article-title":"In vivo analgesic, anti-inflammatory, sedative, muscle relaxant activities, and docking studies of 3',4',7,8-tetrahydroxy-3-methoxyflavone isolated from Pistacia chinensis","volume":"18","author":"Rauf","year":"2024","journal-title":"Drug Target Insights"},{"key":"B51","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.euroneuro.2011.04.002","article-title":"Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence","volume":"21","author":"Sarris","year":"2011","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.biopha.2018.08.117","article-title":"Sedative-hypnotic like effect of 5-methoxyflavone in mice and investigation on possible mechanisms by in vivo and in silico methods","volume":"108","author":"Shanmugasundaram","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B53","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/s41586-020-2408-4","article-title":"Structural basis of the activation of a metabotropic GABA receptor","volume":"584","author":"Shaye","year":"2020","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-444-52002-9.00040-1","article-title":"Anxiolytics","volume-title":"Handbook of clinical neurology, vol. 106 neurobiology of psychiatric disorders","author":"Sinclair","year":"2012"},{"key":"B55","doi-asserted-by":"publisher","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":"B56","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1007\/s11130-010-0180-6","article-title":"Phenolic compounds and vitamin antioxidants of caper (Capparis spinosa)","volume":"65","author":"Tlili","year":"2010","journal-title":"Plant Food Hum. Nutr."},{"key":"B57","first-page":"25","article-title":"Turkish folk medicinal plants, Part VI: ko\u00e7arl\u0131 (ayd\u0131n)","volume":"39","author":"Tuzlac\u0131","year":"2007","journal-title":"J. Fac. Pharm. Istanb."},{"key":"B58","first-page":"5","article-title":"Anksiyetenin n\u00f6robiyolojisi","volume":"1","author":"Uzbay","year":"2002","journal-title":"Klin. Psikiyatri"},{"key":"B59","doi-asserted-by":"publisher","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":"B60","doi-asserted-by":"publisher","first-page":"471","DOI":"10.4088\/jcp.v65n0504","article-title":"How effective is St John's wort? The evidence revisited","volume":"65","author":"Werneke","year":"2004","journal-title":"J. Clin. Psychiatry"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0091-3057(94)90103-1","article-title":"Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea","volume":"47","author":"Wolfman","year":"1994","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B62","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.foodchem.2010.05.039","article-title":"New alkaloids from Capparis spinosa: structure and X-ray crystallographic analysis","volume":"123","author":"Yang","year":"2010","journal-title":"Food Chem."},{"key":"B63","article-title":"Bunalt\u0131 giderici ila\u00e7lar","volume-title":"Temel psikofarmakoloji, t\u00fcrk psikiyatri derne\u011fi","author":"Yaz\u0131c\u0131","year":"2010"},{"key":"B64","article-title":"Resept\u00f6r sonras\u0131 olaylar ve n\u00f6ron plastikli\u011fi","volume-title":"Temel psikofarmakoloji, t\u00fcrk psikiyatri derne\u011fi","author":"Y\u0131lmaz","year":"2010"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e105725","DOI":"10.1371\/journal.pone.0105725","article-title":"Purification and characterization of flavonoids from the leaves of Zanthoxylum bungeanum and correlation between their structure and antioxidant activity","volume":"9","author":"Zhang","year":"2014","journal-title":"PLoS One"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1443173\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T04:32:31Z","timestamp":1724819551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1443173\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":65,"alternative-id":["10.3389\/fphar.2024.1443173"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1443173","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]},"article-number":"1443173"}}