{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:56:24Z","timestamp":1787504184100,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a \u03b2-cyclodextrin\u2013isopulegol inclusion complex (ISO\/\u03b2-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO\/\u03b2-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO\/\u03b2-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1\u03b2 and TNF-\u03b1. ISO and ISO\/\u03b2-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in \u03b2-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.<\/jats:p>","DOI":"10.3390\/foods9050630","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T10:53:59Z","timestamp":1589540039000},"page":"630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antiedematogenic and Anti-Inflammatory Activity of the Monoterpene Isopulegol and Its \u03b2-Cyclodextrin (\u03b2-CD) Inclusion Complex in Animal Inflammation Models"],"prefix":"10.3390","volume":"9","author":[{"given":"Andreza Guedes Barbosa","family":"Ramos","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-9581","authenticated-orcid":false,"given":"Irwin Rose Alencar","family":"de Menezes","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria San\u00e1dia Alexandre","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1959-3286","authenticated-orcid":false,"given":"Renata","family":"Torres Pessoa","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-3215","authenticated-orcid":false,"given":"Luiz Jardelino","family":"de Lacerda Neto","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fab\u00edola","family":"Rocha Santos Passos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Federal University of Sergipe, S\u00e3o Crist\u00f3v\u00e3o, Aracaju - SE 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-4207","authenticated-orcid":false,"given":"Henrique Douglas","family":"Melo Coutinho","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-1236","authenticated-orcid":false,"given":"Marcello","family":"Iriti","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-938X","authenticated-orcid":false,"given":"Lucindo Jos\u00e9","family":"Quintans-J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Physiology, Federal University of Sergipe, S\u00e3o Crist\u00f3v\u00e3o, Aracaju - SE 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2249.2006.03261.x","article-title":"Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1\u03b2 generation","volume":"147","author":"Nielsen","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-ecolsys-040212-092530","article-title":"Inflammation: Mechanisms, costs, and natural variation","volume":"43","author":"Ashley","year":"2012","journal-title":"Annu. Rev. Ecol. Evol. Syst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1034\/j.1600-065X.2002.18602.x","article-title":"Integration of inflammatory signals by rolling neutrophils","volume":"186","author":"Ley","year":"2002","journal-title":"Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1006\/cyto.2000.0816","article-title":"The modulatory role played by TNF-\u03b1 and IL-1\u03b2 in the inflammatory responses induced by carrageenan in the mouse model of pleurisy","volume":"13","author":"Souza","year":"2001","journal-title":"Cytokine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1365-2613.2006.00507.x","article-title":"Chronic inflammation: A failure of resolution?","volume":"88","author":"Lawrence","year":"2007","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/mnfr.201000455","article-title":"The importance of natural product characterization in studies of their anti-inflammatory activity","volume":"55","author":"Gosslau","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00004836-200110000-00006","article-title":"Side effects of corticosteroid therapy","volume":"33","author":"Buchman","year":"2001","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alderson, P., and Roberts, I. (2005). Corticosteroids for acute traumatic brain injury. Cochrane database Syst. Rev.","DOI":"10.1002\/14651858.CD000196.pub2"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2174\/1568010054526331","article-title":"Anti-inflammatory mechanisms of glucocorticoids targeting granulocytes","volume":"4","author":"Caramori","year":"2005","journal-title":"Curr. Drug Targets-Inflam. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s12035-009-8066-z","article-title":"Neuroinflammation and memory: The role of prostaglandins","volume":"40","author":"Hein","year":"2009","journal-title":"Mol. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s10787-016-0270-7","article-title":"Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives","volume":"24","author":"Domiati","year":"2016","journal-title":"Inflammopharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.22192\/ijamr.2016.03.09.007","article-title":"A Review on different types of the Non Steroidal Anti-Inflammatory Drugs (NSAIDs)","volume":"3","author":"Hoque","year":"2016","journal-title":"Int. J. Adv. Multidiscip. Res"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rodrigues, L.B.L.B., Martins, A.O.B.P.B., Ribeiro-Filho, J., Ces\u00e1rio, F.R.A.S., e Castro, F.F., de Albuquerque, T.R., Fernandes, M.N.M., da Silva, B.A.F., J\u00fanior, L.J.Q., and de Sousa Ara\u00fajo, A.A. (2017). Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with \u03b2-cyclodextrin (\u03b2-CD) in mice. Food Chem. Toxicol., 109.","DOI":"10.1016\/j.fct.2017.02.027"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Carneiro, S.B., Duarte, C., \u00cdlary, F., Heimfarth, L., Quintans, S., de Souza, J., Quintans-J\u00fanior, L.J., da Veiga J\u00fanior, V.F., and Neves de Lima, \u00c1.A. (2019). Cyclodextrin\u2013drug inclusion complexes: In vivo and in vitro approaches. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030642"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3797\/scipharm.0808-05","article-title":"Cyclodextrins as drug carrier molecule: A review","volume":"76","author":"Rasheed","year":"2008","journal-title":"Sci Pharm"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"440","DOI":"10.2174\/1389201015666141202101909","article-title":"Physicochemical characterization and analgesic effect of inclusion complexes of essential oil from Hyptis pectinata L. Poit leaves with beta-cyclodextrin","volume":"16","author":"Menezes","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.10.044","article-title":"Cyclodextrins and their pharmaceutical applications","volume":"329","author":"Loftsson","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1517\/13543776.2015.1045412","article-title":"Cyclodextrins: Improving the therapeutic response of analgesic drugs: A patent review","volume":"25","author":"Santos","year":"2015","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.carbpol.2016.06.040","article-title":"Inclusion of terpenes in cyclodextrins: Preparation, characterization and pharmacological approaches","volume":"151","author":"Lima","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4e62","DOI":"10.1016\/j.cbi.2016.05.029","article-title":"A-Terpineol, b-cyclodextrin exerts antihyperalgesic effect in animal model for fibromyalgia aided with docking study","volume":"254","author":"Oliveira","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.biopha.2017.01.158","article-title":"Physico-chemical characterization and antibacterial activity of inclusion complexes of Hyptis martiusii Benth essential oil in \u03b2-cyclodextrin","volume":"89","author":"Andrade","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.phymed.2016.06.007","article-title":"Docking, characterization and investigation of \u03b2-cyclodextrin complexed with citronellal, a monoterpene present in the essential oil of Cymbopogon species, as an anti-hyperalgesic agent in chronic muscle pain model","volume":"23","author":"Santos","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.indcrop.2014.05.055","article-title":"A status review on the medicinal properties of essential oils","volume":"62","author":"Raut","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.22270\/jddt.v9i4-A.3429","article-title":"Isopulegol Ameliorates Dyslipidemia by Modulating Adipokine Secretion in High Fat Diet\/Streptozotocin Induced Diabetic Rats","volume":"9","author":"Kalaivani","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pbb.2007.07.015","article-title":"Central nervous system activity of acute administration of isopulegol in mice","volume":"88","author":"Silva","year":"2007","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00210-009-0429-5","article-title":"Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: Investigation of possible mechanisms of action","volume":"380","author":"Silva","year":"2009","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cbi.2018.07.019","article-title":"Effects of isopulegol in acute nociception in mice: Possible involvement of muscarinic receptors, opioid system and l-arginine\/NO\/cGMP pathway","volume":"293","author":"Piauilino","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1590\/S0102-695X2012005000021","article-title":"Comparative study of the antitumor effect of natural monoterpenes: Relationship to cell cycle analysis","volume":"22","author":"Jaafari","year":"2012","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sankaranarayanan, C., Kalaivani, K., and Isopulegol, A. (2020). Dietary Monoterpene Mitigates Hyperglycemia Mediated Oxidative and Endoplasmic Reticulum Stress in HFD\/STZ Induced Diabetic Rats. Arch. Med. Res.","DOI":"10.1016\/j.arcmed.2020.02.001"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.fitote.2009.06.011","article-title":"Effects of isopulegol on pentylenetetrazol-induced convulsions in mice: Possible involvement of GABAergic system and antioxidant activity","volume":"80","author":"Silva","year":"2009","journal-title":"Fitoterapia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.toxlet.2003.12.033","article-title":"Novel estimates of the exposure to flavouring substances","volume":"149","author":"Cadby","year":"2004","journal-title":"Toxicol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/02652030110071327","article-title":"Comparison of stochastic modelling of the intakes of intentionally added flavouring substances with theoretical added maximum daily intakes (TAMDI) and maximized survey-derived daily intakes (MSDI)","volume":"19","author":"Lambe","year":"2002","journal-title":"Food Addit. Contam."},{"key":"ref_33","first-page":"1","article-title":"WHO food additives series 46: Pulegone and related substances","volume":"50","author":"Speijers","year":"2001","journal-title":"Europe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s10847-016-0633-0","article-title":"Docking and physico-chemical properties of \u03b1-and \u03b2-cyclodextrin complex containing isopulegol: A comparative study","volume":"85","author":"Sousa","year":"2016","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_35","unstructured":"OECD, O. (2001). Guidelines for testing of chemicals, acute oral toxicity-fixed dose procedure. Organ. Econ. Coop. Dev."},{"key":"ref_36","first-page":"320","article-title":"A Hippocratic screen for pure or crude drug materials","volume":"Volume 25","author":"Malone","year":"1962","journal-title":"Proceedings of the Lloydia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Exp. Biol. Med."},{"key":"ref_38","first-page":"261","article-title":"Dextran and carrageenan evoke different inflammatory responses in rat with respect to composition of infiltrates and effect of indomethacin","volume":"221","author":"Lo","year":"1982","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","unstructured":"Lapa, A.J., Souccar, C., Lima-Landman, M.T.R., Castro, M.S., and Lima, T.C.M. (2003). M\u00e9todos de avalia\u00e7\u00e3o da atividade farmacol\u00f3gica de plantas medicinais. Soc. Bras. Plantas Med., 64\u201366."},{"key":"ref_40","first-page":"300","article-title":"Inflammation induced by histamine, serotonin, bradykinin and compound 48\/80 in the rat: Antagonists and mechanisms of action","volume":"191","author":"Maling","year":"1974","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","first-page":"414","article-title":"Prostaglandin E 2-induced inflammation: Relevance of prostaglandin E receptors","volume":"1851","author":"Kawahara","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Molecular Cell Biol. Lipids"},{"key":"ref_42","unstructured":"Syst\u00e8mes, D. (2019, December 20). Dassault Syst\u00e8mes BIOVIA, Discovery Studio visualizer, v. 3.1. Available online: https:\/\/www.3dsbiovia.com\/products\/collaborative-science\/biovia-discovery-studio\/."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nprot.2007.41","article-title":"Chemically induced mouse models of intestinal inflammation","volume":"2","author":"Wirtz","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1182\/blood.V60.3.618.618","article-title":"Cellular and extracellular myeloperoxidase in pyogenic inflammation","volume":"60","author":"Bradley","year":"1982","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.bpa.2003.12.002","article-title":"Mechanisms of the inflammatory response","volume":"18","author":"Sherwood","year":"2004","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.3390\/ijms13021598","article-title":"Antinociceptive and anti-inflammatory effects of octacosanol from the leaves of Sabicea grisea var. grisea in mice","volume":"13","author":"Conserva","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jep.2009.12.030","article-title":"Anti-inflammatory activity of roots of Ecbolium viride (Forsk) Merrill","volume":"128","author":"Lalitha","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_48","first-page":"349","article-title":"Anti-inflammatory treatments for chronic diseases: A review","volume":"12","author":"Laveti","year":"2013","journal-title":"Inflamm. Allergy-Drug Targets (Formerly Curr. Drug Targets-Inflammation Allergy)"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/0015-6264(73)90228-9","article-title":"Monographs on fragrance raw materials","volume":"11","author":"Opdyke","year":"1973","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_50","first-page":"E995","article-title":"Triptolide prevents and attenuates neuropathic pain via inhibiting central immune response","volume":"15","author":"Wang","year":"2012","journal-title":"Pain Physician"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF01967625","article-title":"Carrageenan: A review of its effects on the immune system","volume":"11","author":"Thomson","year":"1981","journal-title":"Agents Actions"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"d12","DOI":"10.2741\/A171","article-title":"Cytokines in acute and chronic inflammation","volume":"2","author":"Feghali","year":"1997","journal-title":"Front Biosci"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.phymed.2012.12.009","article-title":"Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in \u03b2-cyclodextrin","volume":"20","author":"Quintans","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"40378","DOI":"10.1021\/acsami.8b08254","article-title":"Inflammation-Responsive Drug-Conjugated Dextran Nanoparticles Enhance Anti-Inflammatory Drug Efficacy","volume":"10","author":"Lee","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1089\/jmf.2012.0102","article-title":"Anti-inflammatory and anti-ulcer activities of carvacrol, a monoterpene present in the essential oil of oregano","volume":"15","author":"Silva","year":"2012","journal-title":"J. Med. Food"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ejphar.2012.11.040","article-title":"Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10","volume":"699","author":"Kaneto","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.biopha.2017.10.005","article-title":"Anti-edematogenic and anti-inflammatory activity of the essential oil from Croton rhamnifolioides leaves and its major constituent 1,8-cineole (eucalyptol)","volume":"96","author":"Martins","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/153537020523000111","article-title":"Anti-allergic effects of Artemisia iwayomogi on mast cell-mediated allergy model","volume":"230","author":"Kim","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.intimp.2017.07.004","article-title":"Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation","volume":"50","author":"Osman","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1124\/jpet.106.102806","article-title":"Pharmacological and molecular characterization of the mechanisms involved in prostaglandin E2-induced mouse paw edema","volume":"318","author":"Claudino","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"ur Rashid, H., Yiming, X., Ahmad, N., Muhammad, Y., and Wang, L. (2019). Promising anti-inflammatory effects of chalcones via inhibition of cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor \u03baB activities. Bioorg. Chem.","DOI":"10.1016\/j.bioorg.2019.03.033"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.molstruc.2017.11.109","article-title":"Discovery of new class of methoxy carrying isoxazole derivatives as COX-II inhibitors: Investigation of a detailed molecular dynamics study","volume":"1157","author":"Joy","year":"2018","journal-title":"J. Mol. Struct."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nchembio.663","article-title":"(R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2","volume":"7","author":"Duggan","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/bcpt.12221","article-title":"Quintans-J\u00fanior, L.J. Structure\u2013activity relationship of terpenes with anti-inflammatory profile\u2013A systematic review","volume":"115","author":"Almeida","year":"2014","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.compbiomed.2013.02.019","article-title":"Structural modeling and simulation studies of human cyclooxygenase (COX) isozymes with selected terpenes: Implications in drug designing and development","volume":"43","author":"Singh","year":"2013","journal-title":"Comput. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nature10236","article-title":"Structure of the human histamine H 1 receptor complex with doxepin","volume":"475","author":"Shimamura","year":"2011","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0014-2999(84)90454-0","article-title":"The inflammatory reaction in an experimental model of open wounds in the rat. The effect of arachidonic acid metabolites","volume":"97","author":"Lundberg","year":"1984","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Menzies, S.A., Hoff, J.T., and Betz, A.L. (1990). Extravasation of albumin in ischaemic brain oedema. Brain Edema VIII, Springer.","DOI":"10.1007\/978-3-7091-9115-6_74"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jpain.2006.06.010","article-title":"Cytokine profiles during carrageenan-induced inflammatory hyperalgesia in rat muscle and hind paw","volume":"8","author":"Loram","year":"2007","journal-title":"J. Pain"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Odobasic, D., Kitching, A.R., and Holdsworth, S.R. (2016). Neutrophil-mediated regulation of innate and adaptive immunity: The role of myeloperoxidase. J. Immunol. Res., 2016.","DOI":"10.1155\/2016\/2349817"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1590\/S0102-695X2011005000065","article-title":"Citral reduces nociceptive and inflammatory response in rodents","volume":"21","author":"Moreira","year":"2011","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.jep.2012.07.028","article-title":"Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents","volume":"143","author":"Riella","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3390\/molecules18011227","article-title":"A review on anti-inflammatory activity of monoterpenes","volume":"18","author":"Andrade","year":"2013","journal-title":"Molecules"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.fitote.2010.09.012","article-title":"(-)-\u03b1-Bisabolol attenuates visceral nociception and inflammation in mice","volume":"82","author":"De","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Moore, A.R. (2003). Pleural Models of Inflammation. Inflammation Protocols, Springer.","DOI":"10.1385\/1-59259-374-7:123"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/BF01965009","article-title":"A comparison of air pouch, sponge and pleurisy models of acute carrageenan inflammation in the rat","volume":"18","author":"Sedgwick","year":"1986","journal-title":"Agents Actions"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1365-2249.2008.03669.x","article-title":"Effect of tumour necrosis factor-\u03b1 receptor 1 genetic deletion on carrageenan-induced acute inflammation: A comparison with etanercept","volume":"153","author":"Mazzon","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3109\/08830189809043005","article-title":"Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist","volume":"16","author":"Dinarello","year":"1998","journal-title":"Int. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1006\/cyto.1998.0376","article-title":"Generation of inflammatory cytokines in zymosan-induced pleurisy in rats: TNF induces IL-6 and cytokine-induced neutrophil chemoattractant (CINC) in vivo","volume":"10","author":"Utsunomiya","year":"1998","journal-title":"Cytokine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.fct.2018.10.058","article-title":"Monoterpenes modulating cytokines-a review","volume":"123","author":"Quintans","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/00004770-200303000-00009","article-title":"Proinflammatory cytokines induce cyclooxygenase-2 mRNA and protein expression in human pulp cell cultures","volume":"29","author":"Chang","year":"2003","journal-title":"J. Endod."},{"key":"ref_82","first-page":"164","article-title":"The granulomatous inflammatory response. A review","volume":"84","author":"Adams","year":"1976","journal-title":"Am. J. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Roos, D. (2019). Chronic granulomatous disease. NADPH Oxidases, Springer.","DOI":"10.1007\/978-1-4939-9424-3_32"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Rieber, N., Hector, A., Kuijpers, T., Roos, D., and Hartl, D. (2011). Current concepts of hyperinflammation in chronic granulomatous disease. Clin. Dev. Immunol., 2012.","DOI":"10.1155\/2012\/252460"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.autrev.2007.11.025","article-title":"Macrophage activation syndrome in rheumatic disease: What is the role of the antigen presenting cell?","volume":"7","author":"Behrens","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"ref_86","unstructured":"Kumar, V. (2010). Robbins & Cotran-patologia Bases Patol\u00f3gicas das Doen\u00e7as 8a Edi\u00e7\u00e3o, Elsevier."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1590\/S0100-40422008000200032","article-title":"Propriedades e aplica\u00e7\u00f5es recentes das ciclodextrinas","volume":"31","author":"Venturini","year":"2008","journal-title":"Quim. Nova"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"64","DOI":"10.5216\/ref.v13i2.34895","article-title":"Perfil de dissolu\u00e7\u00e3o do tenoxicam em complexos de inclus\u00e3o de beta-ciclodextrinas","volume":"13","author":"Almeida","year":"2016","journal-title":"Rev. Eletr\u00f4nica Farm\u00e1cia"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/9\/5\/630\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:28:55Z","timestamp":1760174935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/9\/5\/630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,14]]},"references-count":88,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["foods9050630"],"URL":"https:\/\/doi.org\/10.3390\/foods9050630","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,14]]}}}