{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:48:48Z","timestamp":1793116128599,"version":"4.5.0"},"reference-count":97,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["304112\/2017-8"],"award-info":[{"award-number":["304112\/2017-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["428719\/2018-0"],"award-info":[{"award-number":["428719\/2018-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004809","name":"Financiadora de Estudos e Projetos","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior","doi-asserted-by":"publisher","award":["10\/2016"],"award-info":[{"award-number":["10\/2016"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda??o de Apoio ? Pesquisa e a Inova??o Tecnol?gica do Estado de Sergipe"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phytol is a diterpene constituent of chlorophyll and has been shown to have several pharmacological properties, particularly in relation to the management of painful inflammatory diseases. Arthritis is one of the most common of these inflammatory diseases, mainly affecting the synovial membrane, cartilage, and bone in joints. Proinflammatory cytokines, such as TNF-\u03b1 and IL-6, and the NF\u03baB signaling pathway play a pivotal role in arthritis. However, as the mechanisms of action of phytol and its ability to reduce the levels of these cytokines are poorly understood, we decided to investigate its pharmacological effects using a mouse model of complete Freund\u2019s adjuvant (CFA)-induced arthritis. Our results showed that phytol was able to inhibit joint swelling and hyperalgesia throughout the whole treatment period. Moreover, phytol reduced myeloperoxidase (MPO) activity and proinflammatory cytokine release in synovial fluid and decreased IL-6 production as well as the COX-2 immunocontent in the spinal cord. It also downregulated the p38MAPK and NF\u03baB signaling pathways. Therefore, our findings demonstrated that phytol can be an innovative antiarthritic agent due to its capacity to attenuate inflammatory reactions in joints and the spinal cord, mainly through the modulation of mediators that are key to the establishment of arthritic pain.<\/jats:p>","DOI":"10.1021\/acs.jnatprod.9b01116","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T09:26:16Z","timestamp":1582536376000},"page":"1107-1117","source":"Crossref","is-referenced-by-count":124,"title":["Phytol, a Chlorophyll Component, Produces Antihyperalgesic,\nAnti-inflammatory, and Antiarthritic Effects: Possible NF\u03baB\nPathway Involvement and Reduced Levels of the Proinflammatory Cytokines\nTNF\u2011\u03b1 and IL\u20116"],"prefix":"10.1021","volume":"83","author":[{"given":"Alexandra\nM. S.","family":"Carvalho","sequence":"first","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]},{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-8905","authenticated-orcid":true,"given":"Luana","family":"Heimfarth","sequence":"additional","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]},{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Willyame Menezes","family":"Pereira","sequence":"additional","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]},{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabri\u0301cio\nSantana","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]},{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irwin R. A.","family":"Menezes","sequence":"additional","affiliation":[{"name":"Regional University of Cariri , , , ,","place":["Crato, Ceara\u0301, Brazil, 63100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique D. M.","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Regional University of Cariri , , , ,","place":["Crato, Ceara\u0301, Brazil, 63100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Picot","sequence":"additional","affiliation":[{"name":"University of La Rochelle , , ,","place":["La Rochelle, France, 17042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Roberto","family":"Antoniolli","sequence":"additional","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jullyana S. S.","family":"Quintans","sequence":"additional","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]},{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucindo J.","family":"Quintans-Ju\u0301nior","sequence":"additional","affiliation":[{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]},{"name":"Federal University of Sergipe , , , ,","place":["Sa\u0303o\nCristo\u0301va\u0303o, SE, Brazil, 49100-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,2,24]]},"reference":[{"issue":"7","key":"2026081719155925300_cit1","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nrrheum.2011.78","article-title":"The Epidemiology of Early Inflammatory Arthritis","volume":"7","author":"Hazes","year":"2011","journal-title":"Nat. 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Osteoarthr","volume":"21","author":"Neogi","year":"2013","journal-title":"Cartil."},{"key":"2026081719155925300_cit4","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nature01661","article-title":"Evolving Concepts\nof Rheumatoid Arthritis","volume":"423","author":"Firestein","year":"2003","journal-title":"Nature"},{"key":"2026081719155925300_cit5","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/j.1749-6632.2002.tb04234.x","article-title":"Mechanisms of Pain in Arthritis","volume":"966","author":"Schaible","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"5","key":"2026081719155925300_cit6","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/aps.2010.32","article-title":"Dexmedetomidine Blocks Thermal Hyperalgesia\nand Spinal Glial Activation\nin Rat Model of Monoarthritis","volume":"31","author":"Xu","year":"2010","journal-title":"Acta Pharmacol.\nSin."},{"key":"2026081719155925300_cit7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the Pathogenesis of Rheumatoid Arthritis","volume":"7","author":"McInnes","year":"2007","journal-title":"Nat. Rev. Immunol."},{"issue":"8","key":"2026081719155925300_cit8","doi-asserted-by":"publisher","first-page":"2701","DOI":"10.1039\/C5FO00548E","article-title":"Green Tea Extract Improves the Oxidative\nState of the Liver and Brain in Rats with Adjuvant-Induced Arthritis","volume":"6","author":"de\nAlmeida Gonc\u0327alves","year":"2015","journal-title":"Food Funct."},{"issue":"2","key":"2026081719155925300_cit9","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1124\/pr.114.009639","article-title":"Cytokines as Therapeutic\nTargets in Rheumatoid Arthritis and Other Inflammatory Diseases","volume":"67","author":"Siebert","year":"2015","journal-title":"Pharmacol. Rev."},{"key":"2026081719155925300_cit10","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1590\/S1516-31802010000500013","article-title":"Biologics\nfor Rheumatoid Arthritis: An Overview of Cochrane Reviews","volume":"128","author":"Singh","year":"2010","journal-title":"Sao Paulo Medical Journal"},{"key":"2026081719155925300_cit11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.18553\/jmcp.2008.14.S4-A.3","article-title":"The Promise\nof Specialty Pharmaceuticals: Are They Worth the Price?","volume":"14","author":"Sullivan","year":"2008","journal-title":"JMCP"},{"key":"2026081719155925300_cit12","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.18553\/jmcp.2014.20.11.1110","article-title":"Predictors of Treatment Initiation with Tumor Necrosis\nFactor-\u03b1 Inhibitors in Patients with Rheumatoid Arthritis","volume":"20","author":"Desai","year":"2014","journal-title":"JMCP"},{"key":"2026081719155925300_cit13","doi-asserted-by":"publisher","first-page":"122","DOI":"10.18553\/jmcp.2016.14261","article-title":"Impact of Out-of-Pocket\nCosts on Prescription Fills Among New Initiators of Biologic Therapies\nfor Rheumatoid Arthritis","volume":"22","author":"Hopson","year":"2016","journal-title":"Journal of Managed\nCare & Specialty Pharmacy"},{"issue":"44","key":"2026081719155925300_cit14","first-page":"59","article-title":"Medicinal\nPlants: Future Source of New Drugs","volume":"59","author":"Shakya","year":"2016","journal-title":"Int. J.\nHerbal Med."},{"issue":"2","key":"2026081719155925300_cit15","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1055\/s-2004-815483","article-title":"Anti-Inflammatory\nCompounds of Plant Origin. Part II. Modulation of pro-Inflammatory\nCytokines, Chemokines and Adhesion Molecules","volume":"70","author":"Calixto","year":"2004","journal-title":"Planta Med."},{"issue":"1","key":"2026081719155925300_cit16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ptr.4686","article-title":"Monoterpenes with\nAnalgesic Activity-A Systematic Review","volume":"27","author":"Guimara\u0303es","year":"2013","journal-title":"Phytother.\nRes."},{"key":"2026081719155925300_cit17","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.phymed.2018.10.028","article-title":"Terpenes\nas Possible Drugs for the Mitigation of Arthritic Symptoms - A Systematic\nReview","volume":"57","author":"Carvalho","year":"2019","journal-title":"Phytomedicine"},{"issue":"10","key":"2026081719155925300_cit18","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1080\/13543776.2017.1349105","article-title":"New\nDrugs or Alternative Therapy to Blurring the Symptoms\nof Fibromyalgia-a Patent Review","volume":"27","author":"Oliveira","year":"2017","journal-title":"Expert Opin.\nTher. Pat."},{"issue":"1","key":"2026081719155925300_cit19","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1194\/jlr.M600050-JLR200","article-title":"Metabolism\nof Phytol to Phytanic Acid in the Mouse, and the Role of PPARalpha\nin Its Regulation","volume":"48","author":"Gloerich","year":"2007","journal-title":"J. Lipid Res."},{"key":"2026081719155925300_cit20","doi-asserted-by":"publisher","first-page":"S59","DOI":"10.1016\/j.fct.2009.11.012","article-title":"Fragrance\nMaterial Review on Phytol","volume":"48","author":"McGinty","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"2026081719155925300_cit21","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.fct.2018.08.032","article-title":"Phytol: A Review of Biomedical Activities","volume":"121","author":"Islam","year":"2018","journal-title":"Food Chem. Toxicol."},{"issue":"4","key":"2026081719155925300_cit22","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.bbrc.2014.08.056","article-title":"A Novel Ether-Linked\nPhytol-Containing Digalactosylglycerolipid in the Marine Green Alga,\nUlva Pertusa","volume":"452","author":"Ishibashi","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026081719155925300_cit23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/949452","article-title":"Antinociceptive and Antioxidant Activities\nof Phytol In Vivo and In Vitro Models","volume":"2013","author":"Santos","year":"2013","journal-title":"Neurosci.\nJ."},{"issue":"4","key":"2026081719155925300_cit24","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/fcp.12049","article-title":"Phytol, a Diterpene\nAlcohol, Inhibits the Inflammatory Response by Reducing Cytokine Production\nand Oxidative Stress","volume":"28","author":"Silva","year":"2014","journal-title":"Fundam. Clin. Pharmacol."},{"issue":"2","key":"2026081719155925300_cit25","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1002\/iub.1952","article-title":"Phytol as an Anticarcinogenic and Antitumoral Agent: An in Vivo Study\nin Swiss Mice with DMBA-Induced Breast Cancer","volume":"71","author":"de\nAlencar","year":"2019","journal-title":"IUBMB Life"},{"issue":"2","key":"2026081719155925300_cit26","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neulet.2012.06.055","article-title":"Anticonvulsant\nEffect of Phytol in a Pilocarpine Model in Mice","volume":"523","author":"Costa","year":"2012","journal-title":"Neurosci. Lett."},{"key":"2026081719155925300_cit27","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.brainres.2013.12.003","article-title":"Anxiolytic-like\nEffects of Phytol: Possible Involvement\nof GABAergic Transmission","volume":"1547","author":"Costa","year":"2014","journal-title":"Brain Res."},{"issue":"2","key":"2026081719155925300_cit28","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.bmcl.2009.11.107","article-title":"Antitubercular Potential\nof Some Semisynthetic Analogues of Phytol","volume":"20","author":"Saikia","year":"2010","journal-title":"Bioorg.\nMed. Chem. Lett."},{"issue":"3","key":"2026081719155925300_cit29","doi-asserted-by":"publisher","first-page":"518S","DOI":"10.1042\/bst025518s","article-title":"NF-Kappa B Activation in Human Knee-Joint\nSynovial\nTissue during the Early Stage of Joint Inflammation","volume":"25","author":"Gilston","year":"1997","journal-title":"Biochem. Soc. Trans."},{"issue":"4","key":"2026081719155925300_cit30","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3109\/08916939808995367","article-title":"AP-1 and\nNF-KappaB Regulation in Rheumatoid Arthritis and Murine Collagen-Induced\nArthritis","volume":"28","author":"Han","year":"1998","journal-title":"Autoimmunity"},{"issue":"1","key":"2026081719155925300_cit31","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1177\/039463201202500124","article-title":"Neuroprotective\nand Anti-Inflammatory\nActivities of Atorvastatin in a Rat Chronic Constriction Injury Model","volume":"25","author":"Chu","year":"2012","journal-title":"Int. J. Immunopathol. Pharmacol."},{"issue":"4","key":"2026081719155925300_cit32","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/ar300","article-title":"NF-Kappa\nB in Rheumatoid Arthritis: A Pivotal Regulator of Inflammation, Hyperplasia,\nand Tissue Destruction","volume":"3","author":"Makarov","year":"2001","journal-title":"Arthritis Res."},{"issue":"4","key":"2026081719155925300_cit33","doi-asserted-by":"publisher","first-page":"R1550","DOI":"10.1152\/ajpregu.1997.273.4.R1550","article-title":"Relations between Functional, Inflammatory,\nand Degenerative Parameters during Adjuvant Arthritis in Rats","volume":"273","author":"Philippe","year":"1997","journal-title":"Am. J. Physiol."},{"issue":"3","key":"2026081719155925300_cit34","doi-asserted-by":"publisher","first-page":"194","DOI":"10.2174\/187220830803150605162745","article-title":"Phytol a Natural Diterpenoid with Pharmacological Applications\non Central Nervous System: A Review","volume":"8","author":"Pereira\nCosta","year":"2015","journal-title":"Recent\nPat. Biotechnol."},{"issue":"1","key":"2026081719155925300_cit35","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0304-3959(87)90088-1","article-title":"The Formalin Test in\nMice: Dissociation between Inflammatory and\nNon-Inflammatory Pain","volume":"30","author":"Hunskaar","year":"1987","journal-title":"Pain"},{"key":"2026081719155925300_cit36","doi-asserted-by":"publisher","first-page":"808460","DOI":"10.1155\/2013\/808460","article-title":"Borneol, a Bicyclic Monoterpene Alcohol,\nReduces Nociceptive\nBehavior and Inflammatory Response in Mice","volume":"2013","author":"Almeida","year":"2013","journal-title":"Sci. World J."},{"issue":"1","key":"2026081719155925300_cit37","doi-asserted-by":"publisher","first-page":"28","DOI":"10.2174\/187152809787582534","article-title":"Molecular Basis of the Anti-Inflammatory\nEffects of Terpenoids","volume":"8","author":"de\nlas Heras","year":"2009","journal-title":"Inflammation Allergy:\nDrug Targets"},{"issue":"2","key":"2026081719155925300_cit38","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0304-3940(94)90025-6","article-title":"Role of Excitatory Amino Acid Receptors\nin the Mediation of the Nociceptive\nResponse to Formalin in the Rat","volume":"174","author":"Hunter","year":"1994","journal-title":"Neurosci. Lett."},{"issue":"6852","key":"2026081719155925300_cit39","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/35093019","article-title":"Molecular Mechanisms of Nociception","volume":"413","author":"Julius","year":"2001","journal-title":"Nature"},{"issue":"2","key":"2026081719155925300_cit40","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.neubiorev.2003.12.003","article-title":"The Orofacial Formalin\nTest","volume":"28","author":"Raboisson","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"issue":"15\u201316","key":"2026081719155925300_cit41","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1007\/s00213-016-4334-6","article-title":"The Effects\nof Morphine on the Temporal Structure of Wistar Rat Behavioral Response\nto Pain in Hot-Plate","volume":"233","author":"Casarrubea","year":"2016","journal-title":"Psychopharmacology (Berl.)"},{"issue":"4","key":"2026081719155925300_cit42","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0031-6997(24)01514-X","article-title":"Animal Models of Nociception","volume":"53","author":"Le\nBars","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"2026081719155925300_cit43","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.neuroscience.2017.06.037","article-title":"D-Limonene Exhibits Superior Antihyperalgesic Effects in a \u03b2-Cyclodextrin-Complexed\nForm in Chronic Musculoskeletal Pain Reducing Fos Protein Expression\non Spinal Cord in Mice","volume":"358","author":"Arau\u0301jo-Filho","year":"2017","journal-title":"Neuroscience"},{"issue":"2","key":"2026081719155925300_cit44","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1007\/s12035-017-0438-1","article-title":"Nanoemulsion Thermoreversible\nPluronic F127-Based Hydrogel Containing Hyptis Pectinata (Lamiaceae)\nLeaf Essential Oil Produced a Lasting Anti-Hyperalgesic Effect in\nChronic Noninflammatory Widespread Pain in Mice","volume":"55","author":"Quintans-Ju\u0301nior","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"2026081719155925300_cit45","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.cbi.2016.05.029","article-title":"\u03b1-Terpineol, a\nMonoterpene Alcohol, Complexed with \u03b2-Cyclodextrin Exerts Antihyperalgesic\nEffect in Animal Model for Fibromyalgia Aided with Docking Study","volume":"254","author":"Oliveira","year":"2016","journal-title":"Chem.-Biol. Interact."},{"issue":"11","key":"2026081719155925300_cit46","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.3109\/13880209.2016.1173066","article-title":"Anti-Rheumatic Activity of Ananas\nComosus Fruit Peel\nExtract in a Complete Freund\u2019s Adjuvant Rat Model","volume":"54","author":"Kargutkar","year":"2016","journal-title":"Pharm. 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