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dc.contributor.authorFerreira, Raquel Teixeira
dc.date.accessioned2023-12-21T19:00:40Z-
dc.date.available2023-12-21T19:00:40Z-
dc.date.issued2016-03-30
dc.identifier.citationFERREIRA, Raquel Teixeira. Mecanismos envolvidos com as atividades antinociceptiva, antiedematogênica e antiinflamatória do flavonoide majoritário das inflorescências de Kalanchoe pinnata (Lam.) Pers. (Folha da fortuna). 2016. 80 f. Tese (Programa Multicêntrico de Pós Graduação em Ciências Fisiológicas) - Instituto de Ciências Biológicas, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2016.por
dc.identifier.urihttps://rima.ufrrj.br/jspui/handle/20.500.14407/10298-
dc.description.abstractKalanchoe pinnata (KP) é popularmente utilizada para tratamento de doenças inflamatórias. Este estudo investigou o potencial antinociceptivo e anti-inflamatório do extrato aquoso das inflorescências de KP (EAFL), a fração acetato de etila (FAcOEt), a fração butanólica (FBuOH), a fração aquosa (FAq) e o flavonoide majoritário [quercetina 3-O-α-Larabinopiranosil (1→β) α-L-ramnopiranosídeo] (KPFV) de KP, assim como possíveis mecanismos de ação. Camundongos albinos, machos (25-35g) foram pré-tratados com EAFL (30-300 mg/kg, s.c.), produzindo inibição dose dependente das contorções induzidas por ácido acético (DI50 164,8 mg/kg), e a administração subcutânea de EAFL (300 mg/kg), FAcOEt (12 mg/kg) ou FBuOH (15 mg/kg) reduziu a migração leucocitária na pleurisia induzida por carragenina em camundongos em 56,1%, 47,3%, 39,6% e 43,1%, respectivamente. Em doses até 240 vezes menores que o EAFL, KPFV (0,3-3,0 mg/kg, s.c.), também foi capaz de inibir a migração leucocitária (DI50 1,78 mg/kg). No teste do edema de orelha induzido por óleo de cróton em camundongos, EAFL (3-30 mg/kg, s.c.) e KPFV (0,3-3,0 mg/kg, s.c.) apresentaram atividade antiedematogênica dose dependente (EAFL - DI50 4,3 mg/kg, KPFV - DI50 0,76 mg/kg). O tratamento com EAFL reduziu a concentração de MPO e de TNF-α no exsudato pleural obtido do teste da pleurisia induzida por carragenina, enquanto o KPFV inibiu ambas as isoformas de cicloxigenase (COX), com CI50 3,8 x 10-5M (22,1 μg/mL) para COX-1 e um máximo de inibição da COX-2 de 43,5% (CI50 >8,4 x10-5M ou 50 μg/mL). O índice de seletividade (COX-1 CI50/COX-2 CI50) foi < 0,44. Estes resultados indicam que EAFL e KPFV produziram atividade anti-inflamatória e antinociceptiva envolvendo a inibição da COX e a redução de TNF-α. Este estudo revela que o principal flavonoide presente nas inflorescências e folhas de KP possui papel importante no uso etnomedicinal desta espécie nos processos de natureza inflamatóriapor
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpor
dc.formatapplication/pdf*
dc.languageporpor
dc.publisherUniversidade Federal Rural do Rio de Janeiropor
dc.rightsAcesso Abertopor
dc.subjectAnti-inflammatoryeng
dc.subjectFlavonoid.eng
dc.subjectKalanchoe pinnatapor
dc.subjectAnti-inflamatóriopor
dc.subjectFlavonoidepor
dc.titleMecanismos envolvidos com as atividades antinociceptiva, antiedematogênica e antiinflamatória do flavonoide majoritário das inflorescências de Kalanchoe pinnata (Lam.) Pers. (folha da fortuna)por
dc.title.alternativeMechanisms underlying the antinociceptive, antiedematogenic, and anti-inflammatory activity of the main flavonoid from Kalanchoe pinnata flowers (Lam.) Pers. (fortune sheet)eng
dc.typeTesepor
dc.description.abstractOtherKalanchoe pinnata (KP) is popularly used for treating inflammatory diseases. This study investigated the antinociceptive and anti-inflammatory potential of the KP flower aqueous extract (KPFE), the ethyl acetate (EtOAcF), butanol (BuOHF) and aqueous (AqF) fractions and the main flavonoid [quercetin 3-O-α-L-arabinopyranosyl (1→β) α-L-rhamnopyranoside] (KPFV) of KP, as well as possible mechanisms of action. Swiss albino mice, male (25-35g) were pretreated with KPFE (30-300 mg/kg, s.c.) producing dose-related inhibition of acetic acid-induced writhing (ID50 164.8 mg/kg), and the subcutaneous administration of KPFE (300 mg/kg), EtOAcF (12 mg/kg), BuOHF (15 mg/kg) or AqF (210 mg/kg) reduced leukocyte migration on carrageenan-induced pleurisy in mice at 56.1%, 47.3%, 39.6% and 43.1%, respectively. At doses of up to 240 times smaller than KPFE, KPFV (0.3-3.0 mg/kg, s.c.), also inhibited leukocyte migration (ID50 1.78 mg/kg). In croton oil-induced ear edema in mice, KPFE (3-30 mg/kg, s.c.) and KPFV (0.3-3.0 mg/kg, s.c.) presented dose-related antiedematogenic activity (KPFE - ID50 4.3 mg/kg, KPFV - ID50 0.76 mg/kg). Treatment with KPFE reduced the MPO and TNF-α concentration in the pleural exudates on carrageenaninduced pleurisy test, while KPFV inhibited both isoforms of cyclooxygenase (COX), with IC50 3.8 x 10-5 M (22.1 μg/mL) for COX-1 and a maximum COX-2 inhibition of 43.5% (IC50 >8.4 x10-5M or 50 μg/mL). The selectivity index (COX-1 IC50/COX-2 IC50) was <0.44. These results indicate that KPFE and KPFV produced anti-inflammatory and antinociceptive activity through the COX inhibition and TNF-α reduction. This study reveals that the main flavonoid in KP flowers and leaves plays an important role in the ethnomedicinal use of this species for healing inflammatory processeseng
dc.contributor.advisor1Vanderlinde, Frederico Argollo
dc.contributor.advisor1ID492.958.967-34por
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/3183716703092107por
dc.contributor.referee1Silva, Alba Cenélia Matos da
dc.contributor.referee2Malvar, David do Carmo
dc.contributor.referee3Pinto, Marcelo Alves
dc.contributor.referee4Côrtes, Wellington da Silva
dc.creator.ID113.952.957-94por
dc.creator.Latteshttp://lattes.cnpq.br/5743321655120732por
dc.publisher.countryBrasilpor
dc.publisher.departmentInstituto de Ciências Biológicas e da Saúdepor
dc.publisher.initialsUFRRJpor
dc.publisher.programPrograma Multicêntrico de Pós-Graduação em Ciências Fisiológicaspor
dc.relation.referencesABU-SOUD, H. M.; HAZEN, S. L. Nitric oxide modulates the catalytic activity of myeloperoxidase. The Journal of Biological Chemistry, v. 275, p. 5425-5430, 2000. AFONSO, P. V.; JANKA-JUNTTILA, M.; LEE, Y. J.; McCANN, C. P.; OLIVER, C. M.; AAMER, K. A.; LOSERT, W.; CICERONE, M. T.; PARENT, C. A. LTB4 is a signalrelay molecule during neutrophil chemotaxis. Developmental Cell, v. 22, p. 1079-1091, 2012. AFZAL, M.; GUPTA, G.; KAZMI, I.; RAHMAN, M.; AFZAL, O.; ALAM, J.; HAKEEM, K. R.; PRAVEZ, M.; GUPTA, R.; ANWAR, F. Anti-inflammatory and analgesic potential of a novel steroidal derivative from Bryophyllum pinnatum. Fitoterapia, v. 83, n. 5, p. 853-858, 2012a. AFZAL, M.; KAZMI, I.; KHAN, R.; SINGH, R.; CHAUHAN, M.; BISH, T.; ANWAR, F. Bryophyllum pinnatum: a review. International Journal of Research in Biological Sciences, v. 2, p. 143-149, 2012b. AGATI, G.; AZZARELLO, R.; POLLASTRI, S.; TATTINI, M. Flavonoids as antioxidants in plants: location and functional significance. Plant Science, v. 196, p. 67-76, 2012. AKINPELU, D. A. Antimicrobial activity of Bryophyllum pinnatum leaves. Fitoterapia, v. 71, p. 193-194, 2000. ALLORGE-BOITEAU, L. Madagascar centre de spéciation et d’origine Du genre Kalanchoe pinnata (Crassulaceae). In: LOURENÇO, W. R. Biogéographie de Madagascar. Paris: Editions de L’ORSTOM, 1996. ALMEIDA, A.P. ; BAYER, B. M. ; HORAKOVA, Z. ; BEAVEN, M. A. Influence of indomethacin and other anti-inflammatory drugs on mobilization and production of neutrophils: studies with carrageenan-induced inflammation in rats. The Journal of Pharmacology and Experimental Therapeutics, v. 214, n. 1, p. 74-79, 1980. ALMEIDA, A. P.; DA SILVA, A. G.; SOUZA, M. L. M.; LIMA, L. M. T. R.; ROSSIBERGMANN, B.; GONÇALVES DE MORAES, V. L.; COSTA, S. S. Isolation and chemical analysis of a fatty acid fraction of Kalanchoe pinnata with a potent lymphocyte suppressive activity. Planta Medica, v. 66, p. 134-137, 2000. ALMEIDA, M. Z. Plantas medicinais, 2 ed. Salvador: Editora EDUFBA, 2003. p. 31, 147, 181. ARANSIOLA, E. F., DARAMOLA, M. O.; IWALEWA, E. O.; SELUWA, A. M.; OLUFOWOBI, O. O. Anti-Diabetic Effect of Bryophyllum pinnatum Leaves. International Journal of Biological, Life Science and Engineering, v. 8, n. 1, 2014. ARCOLINE, T. Plantas Medicinais, saúde e cura pelas plantas. Fitoterapia. São Paulo: On Line, 2003. n. 1, p. 34. 54 ARNHOLD, J. Free radicals – Friends or foes? Properties, functions, and secretion of human myeloperoxidase. Biochemistry, v. 69, p. 4-9, 2004. BABIOR, B. M. The respiratory burst of phagocytes. Journal of Clinical Investigaton. v. 73, p. 599- 601, 1984. BAE, H.; JAYAPRAKASHA, G. K.; JIFON, J.; BHIMANAGOUDA, S. P. Extraction efficiency and validation of an HPLC method for flavonoid analysis in peppers. Food Chemistry, v. 130, p. 751-758, 2012. BAILEY, L. H. The standard Cyclopedia of Horticulture (1&2), The Macmillan Company, New York, 1953. BALUNAS, M. J.; KINGHORN, D. Drug discovery from medicinal plants. Life Sciences, v. 78, p. 431-441, 2005. BALZER, G. Bryophyllum. Ein Beitrag zu seina Pflanzen-morphologie. Berlin- Kleinmachnow, Gartenverlag. GmbH, 1949. BANKS, W. A.; KASTIN, A. J. Saturable transport of peptides across the blood-brain barrier. Life Science, v. 41, p. 1319-1338, 1987. BASBAUM, A. I.; BAUTISTA, D. M.; GRÉGORY, S.; JULIUS, D. Cellular and molecular mechanisms of pain. Cell, v. 139, n. 2, p. 267-284, 2010. BASBAUM, A. I.; JESSELL, T. The Perception of Pain. In: KANDEL, E. R.; SCHWARTZ, J.; JESSELL, T. editors. Principles of Neuroscience. New York: Appleton and Lange; 2000. p. 472-491. BASBAUM, A. I.; JULIUS, D. Novos alvos contra a dor. Scientific American Brasil, v. 50, p. 76-83, 2006. BEERS, M. H.; BERKOW, R. Manual Merck. Ed. Roca Ltda, 2001. BERGSTRÖM, S.; DUNER, H.; VON EULER, U. S.; PERNOW, B.; SJÖVALL, J. Observation on the effects on infusion of prostaglandin E in man. Acta Physiologica Scandinavian, v. 45, p. 145-151, 1959. BENINCÁ, J. P.; MONTANHER, A. B.; ZUCOLOTTO, S. M.; SCHENKEL, E. P.; FRODE, T. S. Evaluation of the anti-inflammatory efficacy of Passiflora edulis. Food Chemistry, v. 104, p. 1097-1105, 2007. BENYHE, S. Morphine: new aspects in the study of an ancient compound. Life Sciences, v. 55, p. 969-979, 1994. BESSON, J. M. The neurobiology of pain. Lancet, v. 353, n. 9164, p. 1610-1615, 1999. BESSON, J. M.; CHAOUCH, A. Peripheral and spinal mechanisms of nociception. Physiology Revision. v. 67, n. 1, p. 67-186, 1987. 55 BETSCHART, C.; VON MANDACH, U.; SEIFERT, B.; SCHEINERA, D.; PERUCCHINI, D.; FINK, D.; GEISSBÜHLER, V. Randomized, double-blind placebocontrolled trial with Bryophyllum pinnatum versus placebo for the treatment of overactive bladder in postmenopausal women. Phytomedicine, v. 20, p. 351-358, 2013. BEVILACQUA, M. P.; POBER, J. S.; MAJEAU, G. R.; FIERS, W.; COTRAN, R. S. GIMBRONE, M. A. Jr. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin. Proceedings of the National Academy of Sciences of the U.S.A., v. 83, n. 12, p. 4533-4537, 1986. BIESALSKI, H. K. Curr. Polyphenols and inflammation: basic interactions. Current Opinion in Clinical Nutrition and Metabolic Care, v. 10, p. 724-728, 2007. BISCHOFF, S. C. Quercetin: potentials in the prevention and therapy of disease. Current Opinion in Clinical Nutrition and Metabolic Care, v. 11, n. 6, p. 733-740, 2008. BISWAS, S. K.; CHOWDHURY, A.; DAS, J.; HOSEN, S. M. Z.; UDDIN, R.; RAHAMAN, S. Literature review on pharmacological potentials of Kalanchoe pinnata (Crassulaceae). African Journal of Pharmacy and Pharmacology, v. 5, n. 10, p. 1258-1262, 2011. BLACK, R. A.; RAUCH, C. T.; KOZLOSKY, C. J.; PESCHON, J. J.; SLACK, J. L.; WOLFSON, M. F.; CASTNER, B. J.; STOCKING, K. L.; REDDY, P.; SRINIVASAN, S.; NELSON, N.; BOIANI, N.; SCHOOLEY, K. A.; GERHART, M.; DAVIS, R.; FITZNER, J. N.; JOHNSON, R. S.; PAXTON, R. J.; MARCH, C. J.; CERRETTI, D. P. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature, v. 385, n. 6618, p. 729-733, 1997. BOITEAU, P. ; ALLORGE-BOUTEAU, L. Kalanchoe (Crassulacées) de Madagascar. Systématique, écophysiologie et phytochimie. Karthala, Paris. 1995. BOND, M. Pain education issues in developing countries and responses to them by the international association for the study of pain. Pain Research & Management, v. 16, p. 404- 406, 2011. BOPDA, O. S. M.; LONGO, F.; BELLA, T. N.; EDZAH, P. M. O.; TAÏWE, G. S.; BILANDA, D. C.; TOM, E. N. L.; KAMTCHOUING, P.; DIMO, T. Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats. Journal of Ethnopharmacology, v.153, p. 400-407, 2014. BOTTING, R. M. Cyclooxygenase: Past, present and future. A tribute to John R. Vane (1927–2004). Journal of Thermal Biology, v. 31, p. 208-219, 2006. BRADLEY, J. R. TNF-mediated inflammatory disease. Journal of Pathology, v. 214, p. 149-160, 2008. BRAMWELL, D. How many plant species are there? Plant Talk. Wiltshire, v. 28, p. 32, 2000. 56 BRASIL. Ministério da saúde. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada (RDC) N° 10, de 9 de março de 2010. Dispõe sobre a notificação de drogas vegetais junto à Agência Nacional de Vigilância Sanitária (ANVISA), 2010. BRESNIHAN, B.; ALVO-GARCIA, J. M.; COBBY, M.; DOHERTY, M.; DOMLJAN, Z.; EMERY, P.; NUKI, G.; PAVELKA, K.; RAU, R.; ROZMAN, B.; WALT, I.; WILLIAMS, B.; AITCHISON, R.; McCABE, D.; MUSIKIC, P. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis and Rheumatism, v. 41, p. 2196-2204, 1998. BRICKS, L. F.; SILVA, C. A. A. Toxicidade dos anti-inflamatórios não-hormonais. Pediatria, v. 27, n. 3, p. 181-193, 2005. BROWNSTEIN, M. J. A brief history of opiates, opioid peptides, and opioid receptors. Proceedings of the National Academy of Sciences of the U.S.A., v. 90, p. 5391-5393, 1993. BUT, P. G.; MURAV´EV, R. A.; FOMINA, V. A.; ROGOVIN, V. V. Antimicrobial activity of myeloperoxidase from neutrophilic peroxisome. Biology Bulletin, v. 29, p. 266- 270, 2002. CALIXTO, J. B. Biodiversidade como fonte de medicamentos. Ciência e Cultura, v. 55, p. 37, 2003. CALIXTO, J. B. Twenty-five years of research on medicinal plants in Latin America: A personal view. Journal of Ethnopharmacology, v. 100, p. 131-134, 2005. CALIXTO, J. B.; SIQUEIRA JR, J. M. Desenvolvimento de medicamentos no Brasil: Desafios. Gazeta Médica da Bahia, v. 78, sup. 1, p. 98-106, 2008. CARMO, J. MESSIAS DO. Idade Média. In: Revista da flora medicinal. Ano XIV (6), junho, Rio de Janeiro, 1947. CARSWELL, E. A.; OLD, L. J.; KASSEL, R. L.; GREEN, S.; FIORE, N.; WILLIAMSON, B. An endotoxin-induced serum factor that causes necrosis of tumors. Proceedings of the National Academy of Sciences of the U.S.A., v. 72, n. 9, p. 3666-3670, 1975. CARVALHO, M. M. M. J.; LODUCA, A.; PORTONI, A. G.; PIMENTA, C. A. M.; FIGUEIRÓ, J. A. B.; BORGES, L. M.; YENG, L. T.; TEIXEIRA, M. J.; KÓVACS, M. J.; MURTA, S. G.; LORDELLO, S. R. M.; GUIMARÃES, S. S. Dor - um estudo multidisciplinar. São Paulo. Summus Editorial, 1999. CARVALHO, W. A.; CARVALHO, R. D. S.; MEDRADO, V. C.; VIANNA, P. T. G. Biologia molecular dos receptores farmacológicos e seus sistemas efetores de interesse em anestesiologia. Revista Brasileira de Anestesiologia, v. 47, s. 2, p. 152-167, 1997. CAZAROLLI, L. H.; ZANATTA, L.; ALBERTON, E. H.; FIGUEIREDO, M. S. R. B. Mini-Reviews in Medicinal Chemistry, v. 8, p. 1429, 2008. 57 CEUSTERS, J.; GODTS, C.; PESHEV, D.; VERGAUWEN, R.; DYUBANKOVA, N.; LESCRINIER, E.; DE PROFT, M. P.; ENDE, W. V. D. Sedoheptulose accumulation under CO2 enrichment in leaves of Kalanchoe pinnata: a novel mechanism to enhance C and P homeostasis? Journal of Experimental Botany Advance, p. 1-11, 2013. CHANDRASEKHARAN, N. V.; DAI, H.; ROOS, K. L.; EVANSON, N. K.; TOMSIK, J.; ELTON, T. S.; SIMMONS, D. L. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. Proceedings of the National Academy of Sciences of the U.S.A., v. 99, v. 21, p. 13926-13931, 2002. CHEN, Q. Methodology in pharmacological study on Chinese materia medica. Beijing: 7 People's Medical Publishing House, 1993. CHERNG, J.-M.; CHIANG, W.; CHIANG, L.-C. Immunomodulatory activities of common vegetables and spices of Umbelliferae and its related coumarins and flavonoids. Food Chemistry, v. 106, n. 3, p. 944-950, 2008. CHIBLI, L. A.; RODRIGUES, K. C. M.; GASPARETTO, C. M.; PINTO, N. C. C.; FABRI, R. L.; SCIO, E.; ALVES, M. S.; VIEIRA, G. D-V.; SOUSA, O. V. Antiinflammatory effects of Bryophyllum pinnatum (Lam.) Oken ethanol extract in acute and chronic cutaneous inflammation. Journal of Ethnopharmacology, v. 154, n. 2, p. 330-338, 2014. CHOI, S. J.; LEE, K. H.; PARK, H. S.; KIM, S. K.; KOH, C. M.; PARK, J. Y. Differential expression, shedding, cytokine regulation and function of TNFR1 and TNFR2 in human fetal astrocytes. Yonsei Medical Journal, v. 46, p. 818-826, 2005. CHUANG, H. H.; PRESCOTT, E. D.; KONG, H.; SHIELDS, S.; JORDT, S. E.; BASBAUM, A. I.; CHAO, M. V.; JULIUS, D. Bradykinin and nerve growth factor release the capsaicin receptor from ptdins(4,5) p2-mediated inhibition. Nature, v. 411, p. 957-962, 2001. CLARK, I. A. How TNF was recognized as a keymechanism of Disease. Cytokine and Growth Factor Reviews, v. 18, n. 3-4, p. 335-343, 2007. CLARK, T. P. The clinical pharmacology of cyclooxygenase-2-selective and dual inhibitors. Veterinary Clinics of North America: Small Animal Practice, v. 36, p. 1061-1085, 2006. COOK, N. C.; SAMMAN, S. Review: flavonoids-chemistry, metabolism, cardioprotective effects and dietary sources. Journal of Nutritional Biochemistry, v. 7, n. 2, p. 66-76, 1996. COPE, A. P.; ADERKA, D.; DOHERTY, M.; ENGELMANN, H.; GIBBONS, D.; JONES, A. C. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis and Rheumatism, v. 35, p. 1160- 1169, 1992. COSTA, S. S.; COUCEIRO, J. N. S. S.; SILVA, I. C. V.; MALVAR, D. C.; COUTINHO, M. A. S.; CAMARGO, L. M. M.; MUZITANO, M. F.; VANDERLINDE, F. A. 58 Flavonoids in the therapy and prophylaxis of flu: a patent review. Expert Opinion on Therapeutic Patents, v. 22, p.1111-1121, 2012. COSTA, R.; FERNANDES, E. S.; MENEZES-DE-LIMA, O. Jr; CAMPOS, M. M.; CALIXTO, J. B. Effect of novel selective non-peptide kinin B(1) receptor antagonists on mouse pleurisy induced by carrageenan. Peptides, v. 27, p. 2967-2975, 2006. COSTA, S. S.; MUZITANO, M. F.; CAMARGO, L. M. M.; COUTINHO, M. A. S. Therapeutic potential of Kalanchoe species: flavonoids and other secondary metabolites. Natural Product Communications, v. 3, p. 2151-2164, 2008. COSTA, S. S.; JOSSANG, A.; BODO, B. Propriétés biologiques et phytochimie des Kalanchoe. In: BOITEAU, P.; ALLORGE- BOITEAU, L. Kalanchoe (Crassulacées) de Madagascar, Systématique, écophysiologie et phytochimie. Paris: Edition Karthala, p.219- 235, 1995. COUTINHO, M. A. S. Kalanchoe pinnata (Crassulaceae) e seus metabólitos: desenvolvimento de formulação farmacêutica e investigação do seu potencial terapêutico em feridas cutâneas. 2013. Tese – Universidade Federal do Rio de Janeiro, Núcleo de Pesquisa de Produtos Naturais. Rio de Janeiro. COUTINHO, M. A. S.; MUZITANO, M. F.; COSTA, S.S. Flavonóides: Potenciais agentes terapêuticos para o processo inflamatório. Revista Virtual de Química, v.1, n. 3, p. 241-256, 2009. COUTINHO, M. A. S., MUZITANO, M. F., CRUZ, E. A., BERGONZI, M.C., KAISER, C.R., TINOCO, L.W., BILIA, A.R., VINCIERI, F.F., ROSSI-BERGMANN, B., COSTA, S.S. Flowers from Kalanchoe pinnata are a Rich Source of T Cell-Suppressive Flavonoids. Natural Product Communications, v. 6, n. 0, p. 1-5, 2012. CRUZ, E. A.; DA-SILVA, S. A. G.; MUZITANO, M. F.; SILVA, P. M. R.; COSTA, S. S.; ROSSI-BERGMANN, B. Immunomodulatory pretreatment with Kalanchoe pinnata extract and its quercitrin flavonoid effectively protects mice against fatal anaphylactic shock. International Immunopharmacology, v. 8, p. 1616-1621, 2008. CRUZ, E. A.; REUTER, S.; MARTIN, H.; DEHZAD, N.; MUZITANO, M. F.; COSTA, S. S.; ROSSI-BERGMANN, B.; BUHL, R.; STASSEN, M.; TAUBE, C. Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease. Phytomedicine, v. 19, n. 2, p. 115-121, 2012. CUI, Y-Q.; JIA, Y-J.; ZHANG, T.; ZHANG, Q-B.; WANG, X-M. Fucoidan Protects against Lipopolysaccharide-Induced Rat Neuronal Damage and Inhibits the Production of Proinflammatory Mediators in Primary Microglia. CNS Neurosciences & Therapeutics, v. 18, p. 827-833, 2012. CUSHNIE, T. P. T.; LAMB, A. J. Antimicrobial activity of flavonoids. International Journal of Antimicrobial Agents, v. 26, p. 343-356, 2005. Di CARLO, G.; MASCOLO, N.; IZZO, A.; CAPASSO, F. Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Science, v. 65, p. 337-353, 1999. 59 DI STASI, L. C. Plantas Medicinais: arte e ciência. São Paulo: Unesp, 1995, 230p. DINARELLO, C. A. Interleukin-1, interleukin-1 receptors and interleukin-1 antagonist. International Reviews of Immunology, v. 16, p. 457-499, 1998. DINARELLO, C. A.; BERNHEIM, H. A.; DUFF, G. W.; LEE, H. V.; NAGABHUSHAN, T. L.; HAMILTON, N. A.; COCEANI, F. Mechanisms of fever induced by recombinant human interferon. Journal of Clinical Investigation, n. 74, p. 906-913, 1984. DINARELLO, C. A.; GELFAND, J. A.; WOLFF, S. M. Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. Journal of the American Medical Association, Chicago, v. 269, n. 14, p. 1829-1835, 1993. DIXON, R. A.; DEY, P.; LAMB, C. J. Phytoalexins: enzymology and molecular biology. Advances in Enzymology and Related Areas of Molecular Biology, v. 55, p. 1-136, 1983. DJOUHRI, L.; AL OTAIBI, N.; KAHLAT, K.; SMITH, T.; SATHISH, J.; WENG, X. Persistent hindlimb inflammation induces changes in activation properties of hyperpolatization-activated current (Ih) in rat C-fiber nociceptores in vivo. Neuroscience, v. 301, p. 121-133, 2015. DRIESSEN, B. Pain: from sign to disease. Clinical Techniques in Equine Practice, v. 6, issue 2, p. 120-125, 2007. DUBNER, R.; BENNET, G. J. Spinal and trigeminal mechanisms of nociception. Annual Review of Neuroscience, v. 6, p. 381-418, 1983. DUBOIS, R. N.; ABRAMSON, S. B.; CROFFORD, L.; GUPTA, R. A.; SIMON, L. S.; Van De PUTTE, L. B.; LIPSKY, P. E. Cyclooxygenase in biology and disease. FASEB Journal, v. 12, n. 12, p. 1063-1073, 1998. ECOTERRAZAS.http://www.ecoterrazas.com/blog/kalanchoe-daigremontiana-el aranto -prodigioso. 14 de Agosto de 2013. EIGLER, A.; SINHA, B.; HARTMANN, G.; ENDRES, S. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunology Today, Cambridge, v. 18, n. 10, p. 487- 492, 1997. EL ABDELLAOUI, S.; DESTANDAU, E.; TORIBIO, A.; ELFAKIR, C.; LAFOSSE, M.; RENIMEL, I.; ANDRÉ, P.; CANCELLIERI, P.; LANDEMARRE, L. Bioactive molecules in Kalanchoe pinnata leaves: extraction, purification, and identification. Analytical and Bioanalytical Chemistry, v. 398, p. 1329-1338, 2010. ENGLAND, S.; BEVAN, S. J.; DOCHERTY, R. J. Prostaglandin E2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. The Journal of Physiology, v. 495, p. 429-440, 1996. 60 ESPOSITO, E.; CUZZOCREA, S. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Current Medicinal Chemistry, v. 16, p. 3152-3167, 2009. ESPOSITO, E.; CUZZOCREA, S. Anti-TNF therapy in the injured spinal cord. Trends in pharmacological sciences, v. 32, n. 2, p. 107-115, 2011. FABRICANT, D. S.; FARNSWORTH, N. R. Environmental Health Perspectives, v. 109, p. 69, 2001. FARQUHAR-SMITH, W. P. Anatomy, physiology and pharmacology of pain. Anaesthesia and Intensive Care Medicine, v. 9, n. 1, p. 3-7, 2007. FELDMAN, M.; BRENNAN, F. M.; MAINI, R. N. Role of cytokines in rheumatoid arthritis. Annual Review of Immunology, v. 14, p. 397-440, 1996. FERNANDES, J. M. Kalanchoe brasiliensis CAMBESS e Kalanchoe pinnata (LAMARCK) PERSOON: Investigação química e avaliação da atividade antiofídica frente ao veneno de Bothrops jararaca. 2015. Dissertação – Universidade Federal do Rio Grande do Norte, Programa de Pós Graduação em Ciências Farmacêuticas. Rio Grande do Norte. FERREIRA, S. H.; BARATA, L. E. S.; SALLES, S. L. M.; QUEIROZ, S. R. R.; NETO, N. E. H.; CORAZZA, R.; FARIAS, R. C. Medicamentos a partir de plantas medicinais no Brasil. Rio de Janeiro, Academia Brasileira de Ciências, 1998. FILHO, M. M. M.; RAHAL, S. C. O uso de antiinflamatórios inibidores COX II seletivos na osteoartrite canina. Veterinária e Zootecnia, v. 15, n. 3, p. 407-415, 2008. FISCHER, L. G.; SANTOS, D.; SERAFIN, C.; MALHEIROS, A.; DELLE MONACHE, F.; DELLE MONACHE, G.; CECHINEL FILHO, V.; DE SOUZA, M. M. Further antinociceptive properties of extracts and phenolic compounds from Plinia glomerata (Myrtaceae) leaves. Biological & Pharmaceutical Bulletin, v. 31, p. 235-239, 2008. FITZGERALD, G. A. COX-2 and beyond: Approaches to prostaglandin inhibition in human disease. Nature reviews. Drug discovery, v. 2, n. 11, p. 879-890, 2003. FITZGERALD, G. A.; PATRONO, C. The coxibs, selective inhibitor of cyclooxygenase-2. New England Journal of Medicine, v. 345, p. 433-442, 2001. FONSECA, A. G. Avaliação da toxicidade do extrato das folhas de Kalanchoe brasiliensis (Crassulaceae) em camundongos swiss. 2014. Tese – Universidade Federal do Rio Grande do Norte. Programa de Pós Graduação em Ciências Farmacêuticas. Rio Grande do Norte. FORMAN, H. J.; TORRES, M. Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. American Journal of Respiratory and Critical Care Medicine, New York, v. 166, p. S4-S8, 2002. 61 FORMICA, J.V.; REGELSON, W. Review of the biology of quercetin and related bioflavonoids, Food and Chemical Toxicology, v. 33, p. 1061-1080, 1995. FRANCO, G. C. N.; MORETTI, D.; CAVALCANTE, P. F. C.; LOPES, L. C. Uma análise crítica sobre viabilidade do uso dos inibidores seletivos de COX II em odontologia. Revista de Odontologia da Universidade Cidade de São Paulo, v. 18, n. 1, p. 75-81, 2006. FRÖDE, T. S.; SOUZA, G. E.; CALIXTO, J. B. The modulatory role played by TNFalpha and IL-1 beta in the inflammatory responses induced by carrageenan in the mouse model of pleurisy. Cytokine, v. 13, p. 162-168, 2001. FUNK, C. D.; FITZGERALD, G. A. COX-2 inhibitors and cardiovascular risk. Journal of Cardiovascular Pharmacology, v. 50, p. 470-479, 2007. GAIND, K. N.; GUPTA, R. L. Alkanes, Alkanols, Triterpens and Sterols of Kalanchoe pinnata. Phytochemistry, p. 11, 1972. GAIND, K. N.; GUPTA, R. L. Identification of Waxes from the Leaves of Kalanchoe pinnata. Planta Medica, v. 23, p. 193-197, 1974. GAUT, J. P.; YEH, G. C.; TRAN, H. D.; BYUN, J.; HENDERSON, J. P.; RICHTER, G. M.; BRENNAN, M. L.; LUSIS, A. J.; BELAAOUAJ, A.; HOTCHKISS, R. S.; HEINECKE, J. W. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proceedings of National Acadademy of Sciences of the U.S.A., v. 98, p. 11961-11966, 2001. GIBSON, P. R. Increased gut permeability in Crohn’s disease: is TNF-α the link? Gut, London, v. 53, n. 12, p. 1724-1725, 2004. GIERSE, J. K.; McDONALD, J. J.; HAUSER, S. D.; RANGWALA, S. H.; KOBOLDT, C. M.; SEIBERT, K. A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors. Journal of Biological Chemistry, v. 271, p. 15810-15814, 1996. GILMAN, A. G.; GOODMAN, L. S.; RALL, T. W.; MURAD, F. Goodman & Gilman's - The pharmacological basis of terapeutics. 12th ed. Rio de Janeiro: Grow-Hill, 2012. GILROY, D. W.; NEWSON, J.; SAWMYNADEN, P. WILLOUGHBY, D. A.; CROXTALL, J. D. A novel role for phospholipase A2 isoforms in the checkpoint control of acute inflammation. FASEB J, v.18, p. 489-498, 2004. GOLDBERG, D. S.; McGEE, S. J. Pain as a global public health priority, BMC PublicHealth, v. 11, p. 770, 2011. GORDALIZA, N. Natural products as leads to anticancer drugs. Clinical and Translational Oncology, v. 9, p. 767-776, 2007. GUARDIA, T.; ROTELLI, A. E.; JUAREZ, A. O.; PELZER, L. E. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Il Fármaco, v. 56, p. 683-687, 2001. 62 GUREJE, O.; VON KORFF, M.; SIMON, G. E.; GATER, R. Persistent pain and wellbeing: a world health organization study in primary care. Jama, v. 280, p. 147-151, 1998. GURIB-FAKIM, A. Medical plants: traditions of yesterday and drugs of tomorrow. Molecular aspects of medicine, v. 27, n. 1, p. 1-93, 2006. HALLIWELL, B.; GUTTERIDGE, J. M. C. Free radicals in biology and medicine. 3.ed. New York: Oxford University Press Inc., 1999. HÄMÄLÄINEN, M.; NIEMINEN, R.; ASMAWI, M. Z.; VUORELA, P.; VAPAATALO, H.; MOILANEN, E. Effects of flavonoids on prostaglandin E2 production and on COX-2 and mPGES-1 expressions in activated macrophages. Planta medica, v. 7, n. 13, p. 1504-1511, 2011. HAMBURGER, M.; HOSTETTMANN, K. Bioactivity in plants: the link between phytochemistry and medicine. Phytochemistry, New York, v. 30, n. 12, p. 3864-3874, 1991. HANADA, T.; YOSHIMURA, A. Regulation of cytokine signaling and inflammation. Cytokine & Growth Factor Reviews, v. 13, p. 413-421, 2002. HANDA, S. S.; CHAWLA, A. S.; SHARMA, A. K. Plants with anti-inflammatory activity. Fitoterapia, LXIII, p. 3-31, 1992. HARBORNE, J. B.; WILLIAMS, C. A. Advances in flavonoid research since 1992. Phytochemistry, Oxford, v. 55, n. 6, p. 481-504, 2000. HARDY, J. D.; WOLFF, H. G.; GOODELL, H. Experimental evidence on the nature of cutaneous hyperalgesia. Journal of Clinical Investigation, v. 29, n. 1, p. 115-140, 1950. HARRIS, R. C.; BREYER, M. D. Physiological regulation of cyclooxygenase-2 in the kidney. American Journal of Physiology Renal Physiology, v. 281, F1-F11, 2001. HAVSTEEN, B. H. The biochemistry and medical significance of the flavonoids. Pharmacology Therapy, v. 96, p. 67-202, 2002. HAZEWINKEL, H. A. W.; VAN DEN BROM, W. E.; THEYSE, L. F. H.; POLLMEIER, M.; HANSON, P. D. Comparison of the effects of firocoxib, carprofen and vedaprofen in a sodium urte crystal induced synovitis model of arthritis in dogs. Research in Veterinary Science, v. 84, p. 74-79, 2008. HEMA, D.; TIDJANI, M.; BASSENE, E.; POSSET, L.; GIONO-BARBER, H. Plantes médicinales africaines XXIV étude de láction anti-inflammatoire de Bryophyllum pinnatum (Crassulaceae). Plantes Médicinales et Phytothérapie, v. 3, p. 231-235, 1986. HILÁRIO, M. O. E.; TERRERI, M. T.; LEN, C. A. Antiinflamatórios não-hormonais: inibidores da ciclooxigenase 2. Journal of Pediatrics, v. 82, n. 5, 2006. HILL, R. S. Fossil evidence for the onset of xeromorphy and scleromorphy in Australian Proteaceae. Australian Systematic Botany, v. 11, p. 391-400, 1998. 63 HOLLMAN, P. C. H.; BATAN, M. B. Absorption, metabolism and health effects of dietary flavonoids in man. Biomedical Pharmacotherapy, v. 51, p. 305-310, 1997. HOSOMI, J. K.; GHELMAN, R.; QUINTINO, M. P.; DE SOUZA, E.; NAKAMURA, M. U.; MORON, A. F. Effects of chronic Bryophyllum pinnatum administration on Wistar rat pregnancy. Forsch Komplementmed, v. 21, n. 3, p. 184-189, 2014. HUTCHINGS, A.; SCOTT, A. H.; LEWIS, G.; CUNNINGHAN, A. Zulu Medicinal Plants, An Inventory. University of Natal Press, Pietermarizburg, South Africa. 1996. IASP - International Association for the Study of Pain. IASP Taxonomy, August 10th, 2011. Available from: http://www.iasp-pain.org. ICHIKAWA, M.; OGURA, M.; IIJIMA, T. Antiallergic flavones glycoside from Kalanchoe pinnatum. Patent 61, 118, 396 [86, 118, 319] (Cl. CO7H17/07), Apl 84/240, 282, 14 nov 1984; 4p- Chemical abstracts, 105, 178423q, 1986. JONES, R. Nonsteroidal Anti-inflamatory drug prescribing: past, present and future. American Journal of Medicine, v. 110, p. 4-7, 2001. JONES, T. C.; HUNT, R. D.; KING, N. W. Patologia Veterinária. São Paulo: Manole, 2000. JOSEPH, B.; SRIDHAR, S.; SANKARGANESH; JUSTINRAJ; EDWIN, B. T. Rare medicinal plant – Kalanchoe pinnata. Research Journal of Microbiology, v. 6, n. 4, p. 322- 327, 2011. JULIUS, D; BASBAUM, A. I. Molecular mechanisms of nociception. Nature, v. 413, p. 203-210, 2001. KALISCH, P. A. An overview of research on the history of leprosy. International Journal of Leprosy, v. 43, n. 2, p. 129-144, 1975. KAMBOJ, A.; SALUJA, A. K. Bryophyllum pinnatum (Lam.) Kurz.: phytochemical and pharmacological profile: a review. Pharmacognosy Review, v. 3, p. 364-374, 2009. KANG, H.; ECKLUND, D.; LIU, M.; DATTA, S. K. Apigenin, a non-mutagenic dietary flavonoids, suppresses lupus by inhibiting autoantigen presentation for expansion of autoreactive Th1 and Th17 cells. Arithrits Research and Therapy, v. 11, p. 1-13, 2009. KAWAI, M.; HIRANO, T.; HIGA, S.; ARIMITSU, J.; MARUTA, M.; KUWAHARA, Y. Flavonoids and related compounds as anti-allergic substances. Allergology, v. 56, p. 113- 123, 2007. KELLY, E. H.; ANTHONY, R. T.; DENNIS, J. B. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. Journal of Nutritional Biochemistry, v. 13, n. 10, p. 572-584, 2002. KIDD, B. L.; URBAN, L. A. Mechanisms of inflammatory pain. British Journal of Anaesthesia, v. 87, n. 1, p. 3-11, 2001. 64 KIEFER, D. M. Today’s chemistry at work. 1997, December, 38. KIM, H. P.; SON, K. H.; CHANG, H. W.; KANG, S. S. J. Pharmacological Science, v. 96, p. 229, 2004. KING, J. N.; DAWSON, J.; ESSER, R. E.; FUJIMOTO, R.; KIMBLE, E. F.; MANIARA, W.; MARSHALL, P. J.; O’BYRNE, L.; QUADROS, E.; TOUTAIN, P. L.; LEE, P. Preclinical pharmacology of rofecoxib: a novel selective inhibitor of cyclooxygenase-2. Journal of Veterinary Pharmacology Therapeutics, v. 32, p. 1-17, 2009. KLEGGETVEIT, I. P.; NAMER, B.; SCHMIDT, R.; HELAS, T.; RÜCKEL, M.; ORSTAVIK, K.; SCHMELZ, M.; JORUM, E. High spontaneous activity of C-nociceptors in painful polyneuropathy. Pain, v. 153, p. 2040-2047, 2012. KLINKHOFF, A. Biological agents for rheumatoid arthritis: targeting both physical function and structural damage. Drugs, v. 64, p. 1267-1283, 2004. KODAMA, M.; DAVIS, M.; FAUSTMAN, D. L. The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis. CMLS, Cellular and Molecular Life Sciences, v. 62, p. 1-13, 2005. KODITHUWAKKU, N. D.; PAN, M.; ZHU, Y. L.; ZHANG, Y. Y.; FENG, Y. D.; FANG, W. R.; LI, Y. M. Antiinflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis. Journal of Ethnopharmacology, v. 150, n. 3, p. 1071-1079, 2013. KOEBERLE, A.; BAUER, J.; VERHOFF, M.; HOFFMANN, M.; NORTHOFF, H.; WERZ, O. Green tea epigallocatechin-3-gallate inhibits microsomal prostaglandin E2 synthase-1. Biochemical and Biophysical Research Communications, v. 388, n. 2, p. 350-354, 2009. KOES, R.; VERWEIJ, W.; QUATTOCCHIO, F. Flavonoids: a colorful model for the regulation and evolution of biochemical pathways. Trends in Plant Sciences, v. 10, n. 5, p. 236-242, 2005. KONG, J. M.; GOH, N. K.; CHIA, L. S.; CHIA, T. F. Recent advances in traditional plant drugs and orchids. Acta Pharmacology Sinica, Beijing, v. 24, n. 1, p. 7-21, 2003. KRAYCHETE, D. C.; CALASANS, M. T.; VALENTE, C. M. L. Citocinas Próinflamatórias e Dor. Revista Brasileira de Reumatologia, v. 46, n. 3, p. 199-206, 2006. KROGEL, C.; ANTONY V. B. Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. The European Respiratory Journal, v. 10, p. 2411-2418, 1997. KUMAR, S.; GUPTA, A.; PANDEY, A. K. Calotropis procera root extract has capability to combat free radical mediated damage. ISRN Pharmacology, v. 2013, pp 8, 2013. KUMAR, V.; ABBAS, A. K.; FAUSTO, N.; ASTER, J. C. ROBBINS and COTRAN– Pathologic Basis of Disease, 8th edition, 2010, Elsevier. 65 KUMMER, C. L.; COELHO, T. C. R. B. Cycloxygenase-2 Inhibitors Nonsteroid Anti- Inflammatory Drugs: Current Issues. Revista Brasileira de Anestesiologia, v. 52, n. 4, p. 498- 512, 2002. KUO, P.C.; KUO, T. H.; SU, C. R.; LIOU, M. J.; WU, T. S. Cytotoxic principles and α- pyrone ringopening derivatives of bufadienolides from Kalanchoe hybrida. Tetrahedron, v. 64, p. 3392-3396, 2008. KVATERNICK, V.; POLLMEIER, M.; FISCHER, J.; HANSON, P. D. Pharmacokinetics and metabolism of orally administered firocoxib, a novel second generation coxib, in horses. Journal of Veterinary Pharmacology Therapeutics, v. 30, p. 208-217, 2007. KWON, J. H.; KIM, J. H.; CHOI, S. E.; PARK, K. H.; LEE, M. W. Inhibitory effects of phenolic compounds from needles of Pinus densiflora on nitric oxide and PGE2 production. Archives of Pharmacal Research, v. 33, n. 12, p. 2011-2016, 2010. LANDOLFI, R.; MOWER, R. L.; STEINER, M. Modification of platelet function and arachidonic acid metabolism by bioflavonoids. Structure-activity relations. Biochemistry and Pharmacology, v. 33, p. 1525-1530, 1984. LANZA, F. Clinical manifestation of myeloperoxidase deficiency. Journal of Molecular Medicine, v. 6, p. 676-681, 1998. LAWRENCE, T.; WILLOUGHBY, D. A.; GILROY, D. W. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. National Review of Immunology, v. 2, n. 10, p. 787-795, 2002. LEE, H. N.; CHO, H. J.; LIM, D. Y.; KANG, Y.-H.; LEE, K. W.; PARK, J. H. Y. Mechanisms by which licochalcone e exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and lipopolysaccharide-stimulated murine macrophages. International Journal of Molecular Sciences, v. 14, n. 6, p. 10926-10943, 2013. LEES, P.; LANDONI, M. F.; GIRAUDEL, J.; TOUTAIN, P. L. Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest. Journal of Veterinary of Pharmacology and Therapeutics, v. 27, p. 479-490, 2004. LIMA, C. M.; LIMA, A. K.; MELO, M. G. D. et al. Bioassay-guided evaluation of Dioscorea villosa - an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach. BMC Complementary and Alternative Medicine, v. 13, article 195, 2013. LIMA, D. R. Medicamentos: passado, presente e futuro. In: Lima DR, editor. Manual de Farmacologia Clínica, Terapêutica e Toxicologia. 1994. Rio de Janeiro: Guanabara Koogan; p. 13. LIU, K. C. S.; YANG, S. L.; ROBERTS, M. F.; PHILLIPSON, J. D. Eupafolin rhamnosides from Kalanchoe gracilis. Journal of Natural Products, v. 52, p. 970-974, 1989. LÓPEZ- POSADAS, R.; BALLESTER, I.; ABADÍA-MOLINA, A. C.; SUÁREZ, M. D.; ZARZUELO, A.; MARTÍNEZ-AUGUSTIN, O.; DE MEDINA, F. S. Biochemistry and Pharmacology, v. 76, p. 495, 2008. 66 LOWERY, C. L.; HARDMAN, M. P.; MANNING, N.; HALL, R. W.; ANAND, K. J. Neurodevelopmental changes in fetal pain. Seminars in Perinatology, v. 31, n. 5, p. 275-282, 2007. LÜTTGE, U. Ecophysiology of Crassulacean Acid Metabolism. Annals of Botany, v. 93, p. 629-652, 2004. MA, Y.; ZENG, M.; SUN, R.; HU, M. Disposition of flavonoids impacts their efficacy and safety. Current Drug Metabolism, v. 15, n. 9, p. 841-864, 2014. MACIEL, M. A. M. Croton cajucara: Uma escolha etnobotânica. 1997. Tese – Universidade Federal do Rio de Janeiro, Instituto de Química. Rio de Janeiro. MACIEL, M. A. M.; PINTO, A. C.; VEIGA JR, V. F.; ECHEVARRIA, A.; GRYNBERG, N. F. Plantas medicinais: a necessidade de estudos multidisciplinares. Química Nova, v. 25, n. 3, p. 429-438, 2002a. MACIEL, M. A. M.; PINTO, A. C.; VEIGA JR, V. F.; MARTINS, J. R.; GRYNBERG, N. F.; ECHEVARRIA, A.; LAPPA, A. J.; VANDERLINDE, F. A. Croton cajucara as an alternative to tradicional medicine in a modern health system. Recent Progress in Medicinal Plants. Phytochemistry and Pharmacology, v. 8, p. 502-517, 2002b. MAHOMOODALLY, M. F.; GURIB-FAKIM, A.; SUBRATTY, A. H. Antimicrobial activities and phytochemical profiles of endemic medicinal plants of Mauritius. Pharmaceutical Biology, v. 43, n. 3, p. 237-242, 2005. MANCINI, A. D.; DI BATTISTA, J. A. The cardinal role of the phospholipase A2/cyclooxygenase-2/ prostaglandin e synthase/ prostaglandin E2 (PCPP) axis in inflammostasis. Inflammation Research, v. 60, n. 12, p. 1083-1092, 2011. MANI, R. N.; BREEDVELD, F. C.; KALDEN, J. R.; SMOLEN, J. S.; DAVIS, D.; MACFARLANE, J. D.; ANTONI, C.; LEEB, B.; ELLIOTT, M. J.; WOODY, J. N.; SCHAIBLE, T. F.; FELDMANN, M. Therapeutic efIcacy of multiple intravenous infusions of anti-tumor necrosis fator alpha monoclonal antibody combined with methotrexate in rheumatoid arthritis. Arthritis and Rheumatism, v. 41, p. 1552-1563, 1998. MARCHAND, L. L. Cancer preventive effects of flavonoids- a review. Biomedicine & Pharmacotherapy, v. 56, p. 296-301, 2002. MARK, K. S.; TRICKLER, W. J.; MILLER, D. W. Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. The Journal of Pharmacology and Experimental Therapeutics, v. 297, n. 3, p. 1051-1058, 2001. MARRIAGE, P. B.; WILSON, D. G. Analysis of the Organic Acids of Bryophyllum calycinum. Canadian Journal of Biochemistry, v. 49, p. 82-95, 1971. MARSHALL, E. J. P.; BROWN, V. K.; BOATMAN, N. D.; LUTMAN, P. J. W.; SQUIRE, G. R.; WARD, L. K. The role of weed in supporting biological diversity whithin crop fields. Weed Research, v. 43, p. 77-89, 2003. 67 MATHEWS, K. A.; DOHERTY, T.; DYSON, D. H.; WILCOCK, B.; VALLIANT, A. Nephrotoxicity in dogs associated with methoxyflurane anesthesia and flunixin meglumine analgesia. The Canadian Veterinary Journal, v. 31, p. 766-771, 1990. MAZZON, E.; CUZZOCREA, S. Role of TNF-alpha in lung tight junction alteration in mouse model of acute lung inflammation. Respiratory Research, v. 8, p. 75, 2007. McADAM, B. F.; MARDINI, I. A.; HABIB, A.; BURKE, A.; LAWSON, J. A.; KAPOOR, S.; FITZGERALD, G. A. Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. The Journal of Clinical Investigation, v. 105, p. 1473-1482, 2000. McDERMOTT, M. F. TNF and TNFr biology in health and disease. Cellular and Molecular Biology (Noisy-le-grand), v. 47, p. 619-635, 2001. McMAHON, S.; KOLTZENBURG, M. The changing role of primary afferent neurons in pain. Pain, v. 43, n. 3, p. 269-272, 1990. MEDZHITOV, V. R. Origin and physiological roles of inflammation. Nature, v. 454, n. 7203, p. 428-435, 2008. MELZACK, R.; WALL, P. D. Pain mechanisms: a new theory. Science, v. 150, p. 971- 979, 1965. MESQUITA, L. A. F. Estudo da cicatrização cutânea causada pelo laser de CO2 ultrapulsado em retalho dorsal de ratos. 2002. Dissertação – Faculdade Evangélica do Paraná. Curitiba. METCALEF C. R., CHALK, L. Anatomy of the Dicotyledons І. Oxford at the Clarendon Press; 1950. METHE, H.; ZIMMER, E.; GRIMM, C.; NABAUER, M.; KOGLIN, J. Evidence for a role of toll-like receptor 4 in development of chronic allograft rejection after cardiac transplantation. Transplantation, Baltimore, v. 78, n. 9, p. 1324-1331, 2004. MIDDLETON, E. J. Effect of plant flavonoids on immune and inflammatory cell function. Advances in Experimental Medicine and Biology, v. 439, p. 175-182, 1998. MIDDLETON, E.; KANDASWAMI, C.; THEOHARIDES, T. C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacological Reviews, v. 52, p. 673, 2000. MILAD, R.; EL-AHMADY, S.; SINGAB, A. N. Genus Kalanchoe (Crassulaceae): A Review of Its Ethnomedicinal, Botanical, Chemical and Pharmacological Properties. European Journal of Medicinal Plants, v. 4, n. 1, p. 86-104, 2014. MILLER, A. L. Antioxidant flavonoids: Structure, function and Clinical Usage. Alternative Medicine Review, v. 1, p. 103-111, 1996. 68 MIRANDA, L. T. G. S. Uso da Tintura de Arnica em Feridas Cutâneas Abertas em Ratos. 2001. Dissertação – Universidade Federal de São Paulo, Programa de Pós-Graduação em Técnica Operatória e Cirurgia Experimental. São Paulo. MISRA, S.; DIXIT, S. N. Antifungal activity of leaf extract of some higher plants. Acta Botanica Indica, v. 7, p. 147-150, 1979. MOHAMMADPOUR, H.; POURFATHOLLAH, A. A.; ZARIF, M. N.; TAHOORI, M. T. TNF-α modulates the immunosuppressive effects of MSCs on dendritic cells and T cells. International Immunopharmacology, v. 28, p. 1009-1017, 2015. MONTENEGRO, M. R.; FECHIO, M. Inflamações: conceitos gerais e inflamação aguda. In: FRANCO, M.; MONTENEGRO, M. R.; BRITO, T.; BACCHI, C. E.; ALMEIDA, P. C. (Org.). Patologia: Processos gerais. 5 ed. São Paulo: Atheneu, 2010. cap. 7. MONTGOMERY, S. L.; BOWERS, W. J. Tumor necrosis fator alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system. Jounal of Neuroimmune Pharmacology, v. 7, n. 1, p. 42-59, 2012. MORELAND, L. W.; SCHIFF, M. H.; BAUMGARTNER, S. W.; TINDALL, E.; FLEISCHMANN, R. M.; BULPITT, K. J.; WEAVER, A. L.; KEYSTONE, E. C.; FURST, D. E.; MEASE, P. J.; RUDERMAN, E. M.; HORWITZ, D. A.; ARKFELD, D. G.; GARRISON, L.; BURGE, D. J.; BLOSCH, C. M.; LANGE, M. L.; McDONNELL, N. D.; WEINBLATT, M. E. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Annals of Internal Medicine, v.130, p. 478-486, 1999. MORIKAWA, K.; NONAKA, M.; NARAHARA, M. et al. Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sciences, v. 74, n. 6, p. 709-721, 2003. MORS, W. B.; RIZZINI, C. T.; PEREIRA, N. A. Medicinal Plants of Brazil. Reference Publications, Inc. (Ed). Algonac, Michigan, USA, 2000. MOURÃO, R. H. V.; SANTOS, F. O.; FRANZOTTI, E. M.; MORENO, M. P. N.; ANTONIOLLI, A. R. Antiinflammatory activity and acute toxicity (LD50) of the juice of Kalanchoe brasiliensis comb. leaves picked before and during blooming. Phytotherapy Research, v.1, p. 352-354, 1999. MURPHY, P. G.; RAMER, M. S.; BORTHWICK, L.; GALDIE, J.; RICHARDSON, P. M.; BISBY, M. A. Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice. The European Journal of Neuroscience, v. 11, p. 2243-2253, 1999. MURRAY, J. J.; TONNEL, A. B.; BRASH, A. R.; ROBERTS, L. J. II; GOSSET, P.; WORKMAN, R.; CAPRON, A.; OATES, J. A. Release of prostaglandin D2 into human airways during acute antigen challenge. The New England Journal of Medicine, v. 315, p. 800-804, 1986. MUZITANO, M. F.; BERGONIZ, M. C.; DE MELO, G. O.; LAGE, C. L. S.; BILIA, A. R.; VINCIERI, F. F.; ROSSI-BERGMANN, B.; COSTA, S. S. Influence of cultivation 69 conditions, season of collection and extraction method on the content of antileishmanial flavonoids from Kalanchoe pinnata. Journal of Ethnopharmacology, v. 133, p. 132-137, 2011. MUZITANO, M. F.; CRUZ, E. A.; ALMEIDA, A. P.; DA-SILVA, S. A. G.; KAISER, C. R.; GUETTE, C.; ROSSI-BERGMANN, B.; COSTA, S. S. Quercitrin: an antileishmanial flavonoid glycoside from Kalanchoe pinnata. Planta Medica, v. 72, p. 81-83, 2006. NAIR, M. P.; MAHAJAN, S.; REYNOLDS, J. L. et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-�􀟚 system. Clinical and Vaccine Immunology, v. 13, n. 3, p. 319-328, 2006. NARABA, H.; MURAKAMI, M.; MATSUMOTO, H.; SHIMBARA, S.; UENO, A.; KUDO, I.; OH-ISHI, S. Segregated coupling of phospholipases A2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages, Journal of Immunology, v. 160, p. 2974-2982, 1998. NATHAN, C. Points of control in inflammation. Nature, v. 420, p. 846-885, 2002. NASCIMENTO, L. B. S.; LEAL-COSTA, M. V.; COUTINHO, M. A. S.; MOREIRA, N. S.; LAGE, C. L. S.; BARBI, N. S.; COSTA, S. S.; TAVARES, E. S. Increased Antioxidant Activity and Changes in Phenolic Profile of Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) Specimens Grown Under Supplemental Blue Light. Photochemistry and Photobiology, v. 89, p. 391-399, 2013. NASCIMENTO, L. B. S.; MOREIRA, N. S.; LEAL-COSTA, M. V.; COSTA, S. S.; TAVARES, E. S. Induction of wound-periderm-like tissue in Kalanchoe pinnata (Lam.) Pers.(Crassulaceae) leaves as a defence response to high UV-B radiation levels. Annals of Botany, v. 116, p. 763-769, 2015a. NASCIMENTO, L. B.; LEAL-COSTA, M. V.; MENEZES, E. A.; LOPES, V. R.; MUZITANO, M. F.; COSTA, S. S.; TAVARES, E. S. Ultraviolet-B radiation effects on phenolic profile and flavonoid contente of Kalanchoe pinnata. Journal of Photochemistry and Photobiology B: Biology, v. 148, p. 73-81, 2015b. NASRI, H.; SHIRZAD, H. Toxicity and safety of medicinal plants. Journal of Herbal Medicine and Pharmacology, v. 2, p. 21-22, 2013. NAUSEEF, W. M. Myeloperoxidase in human neutrophil host defence. Cellular Microbiology, v. 16, n. 8, p. 1146-1155, 2014. NAYAK, B. S.; MARSHALL JR, I. G. Wound healing potential of ethanolic extract of Kalanchoe pinnata Lam. Leaf - A preliminary study. Indian Journal of Experimental Biology, v. 48, p. 572-576, 2010. NESTLER, E. J.; HYMAN, S. E.; MALENKA, R. C. Molecular neuropharmacology: a foundation for clinical neuroscience. 2001. New York: Macgraw-Hill. 70 NEUGEBAUER, V.; SCHAIBLE, H-G.; SCHMIDT, R. F. Sensitization of articular afferents to mechanical stimuli by bradykinin. Pflügers Archives, v. 415, p. 330-335, 1989. NEVE, J.; PARIJ, N.; MOGUILEVSKY, N. Inhibition of the myeloperoxidase chlorinating activity by non-steroidal anti-inflammatory drugs investigated with a human recombinant enzyme. European Journal of Pharmacology, v. 417, p. 37-43, 2001. NEWMAN, D. J.; CRAGG, G. M. Natural products as sources of new drugs over the last 25 years. Journal of Natural Products, v. 70, p. 461, 2007. NGUELEFACK, T. B.; NANA, P.; ATSAMO, A. D.; DIMO, T.; WATCHO, P.; DONGMO, A. B.; TAPONDJOU, L. A.; NJAMEN, D.; WANSI, S. L.; KAMANYI, A. Analgesic and anticonvulsivant effects of extracts from the leaves of Kalanchoe crenata (Andrews) Hawort (Crassulaceae). Journal of Etnopharmacology, v. 106, n. 1, p. 70-75, 2006. NIJVELDT, R. J.; NOOD, E.; HOORN, D. E. C.; BOELENS, P. G.; NORREN, K.; LEEUWEN, P. A. M. American Journal of Clinical Nutrition, v. 74, p .418, 2001. O’BYRNE, J. O.; DALGLEISH, A. G. Chronic immune activation and inflammation as the cause of malignancy. British Journal of Cancer, v. 85, p. 473-483, 2001. OJEWOLE, J. A. O. Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract. Journal of etnopharmacology, v. 99, n. 1, p. 13-19, 2005. OKWU, D. E.; NNAMDI, F. U. Two novel flavonoids from Bryophyllum pinnatum and their antimicrobial activity. Journal of Chemistry and Pharmacological Research, v. 3, n. 2, p. 1-10, 2011. OKWU, E.; JOSIAH, C. Evaluation of the chemical composition of two Nigerian medicinal plants. African Journal of Biotechnology, v. 5, p. 357-361, 2006. OLIVEIRA, A. B. Espectrofotometria no controle de qualidade de fitoterápicos da Schinus terebinyhifolius raddi: uso de marcadores. 2001. Dissertação – Universidade Federal do Maranhão, Centro de Ciências Biológicas e da Saúde. São Luís. O’SHEA, J. J.; GADINA. M.; KANNO, Y. Cytokine Signaling: Birth of a Pathway. Journal of Immunology, v. 187, n. 11, p. 5475-5478, 2011. PAL, R. S.; ARIHARASIVAKUMAR, G.; GIRHEPUNJHE, K.; UPUDHAY, A. In vitro antioxidative activity of phenolic and flavonoids compounds extracted from seeds of Abrus precatorius. International Journal of Pharmacy and Pharmaceutical Sciences, v. 1, p. 136-140, 2009. PAL, S.; CHAUDHURI, A. K. N. Anti-inflammatory action of Bryophyllum pinnatum leaf extract. Fitoterapia, v. 6, p. 527-533, 1990. 71 PAL, S.; CHAUDHURI, A. K. N. Studies on the anti-ulcer activity of a Bryophyllum pinnatum leaf extract in experimental animals. Journal of Ethnopharmacology, v. 33, p. 97- 102, 1991. PAL, S.; SEN, T.; CHAUDHARI, A. K. N. Neuropsychopharmacological profile of the methanolic fraction of Bryophyllum pinnatum leaf extract. Journal of Pharmacy and Pharmacology, v. 51, p. 313-318, 1999. PALLADINO, M. A.; BAHJAT, F. R.; THEODORAKIS, E. A.; MOLDAWER, L. L. Anti TNF-α therapies: the next generation. Natural Reviews Drug Discovery, London, v. 2, p. 736-746, 2003. PANDEY, K. Anti-staphylococcal activity of a pan-tropical aggressive and obnoxious weed Pariheniumhisterophorus: an in vitro study. National Academy Science Letters, v. 30, n. 11-12, p. 383-386, 2007. PANOSSIAN, A.; HAMM, R.; KADIOGLU, O.; WIKMAN, G.; EFFERTH, T. Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells. Frontiers in Neuroscience, v. 7, n. 16, 2013. PAPICH, M. G. An update on nonsteroidal anti-inflammatory drugs (NSAIDs) in Small Animals. Veterinary Clinics of North America: Small Animal Practice, v. 38, p. 1243-1266, 2008. PARVEEN, Z.; DENG, Y.; SAEED, M. K.; DAI, R.; AHAMAD, W.; YU, Y. H. Antiinflammatory and analgesic activities of Thesium chinense Turcz extracts and its major flavonoids, kaempferol and kaempferol-3-�-glucoside. Yakugaku Zasshi, v. 127, n. 8, p. 1275-1279, 2007. PASSOS, G. F.; FERNANDES, E. S.; DA CUNHA, F. M.; FERREIRA, J.; PIANOWSKI, L. F.; CAMPOS, M. M.; CALIXTO, J. B. Antiinflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. Journal of Ethnopharmacology, v. 110, n. 2, p. 323-333, 2007. PAYNE, R. Limitations of NSAIDs for pain management: toxicity or lack of eficacy? The Journal of Pain, v. 1, p. 14-18, 2000. PECCHI, E.; DALLAPORTA, M.; JEAN, A.; THIRION, S.; TROADEC, J. Prostaglandins and sickness behavior: old story, new insights. Physiology Behavior, v. 97, p. 279-292, 2009. PENNICA, D.; HAYFLICK, J. S.; BRINGMAN, T. S.; PALLADINO, M. A.; GOEDDEL, D. V. Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proceedings of the National Academy of Sciences of the U.S.A., v. 82, n. 18, p. 6060-6064, 1985. PERL, E. R. Myelinated afferent fibres innervating the primate skin and theirresponse to noxious stimuli. The Journal of Physiology, v. 197, p. 593-615, 1968. 72 PERL, E. R. Function of dorsal root ganglion neurons: an overview. In: Scott, S.A.(Ed.), Sensory Neurons: Diversity, Development and Plasticity. Oxford UniversityPress, New York, p. 3-23, 1992. PHATAK, R. S.; HENDRE, A. S. In-vitro Antiurolithiatic Activity of Kalanchoe pinnata Extract. International Journal of Pharmacognosy and Phtytochemical Research, v.7, n. 2, p. 275-279, 2015. PIXABAY. http://pixabay.com/pt/planta-de-goethe-flor-269758. PLANGGER, N.; RIST, L.; ZIMMERMANN, R.; MANDACH, U. V. Intravenous tocolysis with Bryophyllum pinnatum is better tolerated than beta-agonist application. European Journal of Obstetrics & Gynecology and Reproductive Biology, v. 124, p. 168-172, 2006. PORTER, D. G. Ethical scores for animal experiments. Nature, v. 356, n. 6365, p.101- 102, 1992. PRASAD, A. K.; KUMAR, S.; IYER, S. V.; SUDANI, R. J.; VAIDYA, S. K. Pharmacognostical, phytochemical and pharmacological review on Bryophyllum pinnata. International Journal of Pharmaceutical & Biological Archives, v. 3, p. 423-433, 2012. QUAZI MAJAZ, A.; TATIYA, A. U.; KHURSHID, M.; NAZIM, S.; SIRAJ, S. The miracle plant (Kalanchoe pinnata): a phytochemical and pharmacological review. International Journal of Research in Ayurveda & Pharmacy, v. 2, p. 1478-1482, 2011a. QUAZI MAJAZ, A.; NAZIM, S.; ASIR, Q.; SHOEB, Q.; BILIAL, G. M. Screening of in vitro antihelmentic activity of Kalanchoe pinnata roots. International Journal of Ayurveda Research Pharmacology, v. 2, n. 1, p. 221-223, 2011b. RAHMATI, M.; MOBASHERI, A.; MOZAFARI, M. Inflammatory mediators in osteoarthritis: A critical review of the state-of-the-art, current prospects, and future challenges. Bone, v. 85, p. 81-90, 2016. RAMESOVÁ, S.; SOKOLOVÁ, R.; DEGANO, I.; BULÍCKOVÁ, J.; ZABKA, J.; GÁL, M. On the stability of the bioactive flavonoids quercetin and luteolin under oxygen-free conditions. Analytical and Bioanalytical Chemistry, v. 402, p. 975-982, 2012. RANG, H. P.; DALE, M. M.; RITTER, J. M.; FLOWER, R. J. Farmacologia. 2007. 6ª ed., Rio de Janeiro: Elsevier. RATES, S. M. K. Plants as source of drugs. Toxicon, Elmsford, v. 39, p. 603-613, 2001. RATHER, L. J. Disturbance of function (functio laesa): the legendary fifth cardinal sign of inflammation, added by Galento the four cardinal signs of Celsus. Bulletin of the New York Academy of Medicine, v. 47, n. 3. p. 303-322, 1971. REARDON, D. P.; ANGER, K. E.; SZUMITA, P. M. Pathophysiology, assessment, and management of pain in critically ill adults. American Journal of Health System Pharmacy, v. 72, p. 1531-1543, 2015. 73 RENISUS – Ministério da Saúde. Fevereiro de 2009. REXED, B. The cytoarchitectonic organization of the spinal cord in the cat. Journal Comparative Neurology, v. 96, n. 3, p. 414-495, 1952. RICCIOTTI, E.; FITZGERALD, G. A. Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis and Vascular Biology, v. 31, p. 986-1000, 2011. RICE-EVANS, C. A.; MILLER, N. J.; BOLWELL, P. G.; BROAMLEY, P. M.; PRIDHAM, J. B. The relative antioxidant activities of plantderived polyphenolic flavonoids. Free Radical Research, v. 22, n. 4, p. 375-383, 1995. ROBAK, T.; GLADALSKA, A.; STEPIEN, H. The tumour necrosis fator family of receptors/ligands in the serum of patients with rheumatoid arthritis. European Cytokine Network, v. 9, n. 2, p. 145-154, 1998. ROBERTS, L. J. II; SWEETMAN, B. J. LEWIS, R. A.; AUSTEN, K. F.; OATES, J. A. Increased production of prostaglandin D2 in patients with systemic mastocytosis. The New England Journal of Medicine, v. 303, p. 1400-1404, 1980. ROBBINS; COTRAN. Patologia: Bases patológicas das doenças. 8ª Edição. Rio de Janeiro: Elsevier, 2010. 1458 p. ROGERIO, A. P.; KANASHIRO, A.; FONTANARI, C.; DA SILVA, E. V.; LUCISANO-VALIM, Y. M.; SOARES, E. G.; FACCIOLI, L. H. Antiinflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflammation Research, v. 56, n. 10, p. 402-408, 2007. ROITT, I.; BROSTOFF, J.; MALE, D. Immunologia. 5 ed. São Paulo: Manole, 1999. 423p. ROSEN, H.; MICHEL B. Redundant contribution of myeloperoxidase dependent systems to neutrophil-mediated killing of Escherichia coli. Infection and Immunity, v. 65, p. 4173-4178, 1997. ROSSI-BERGMANN, B.; COSTA, S. S.; MORAES, V. L. G. Brazilian medicinal plants: a rich source of immunomodulatory substances. Ciência e Cultura, v. 49, p. 395-401, 1997. ROSSI-BERGMANN, B.; COSTA, S.S.; BORGES, M. B. S., DA SILVA, S. A. G.; NOLETO, G. R.; SOUZA, M. L. M.; MORAES, V. L. G. Immunosuppressive effect of the aqueous extract of Kalanchoe pinnata in mice. Phytotherapy Research, v. 8, p. 399-402, 1994. ROTELLI, A. E.; GUARDIA, T.; JUÁREZ, A. O.; ROCHA, N. E. de L. A., PELZER, L. E. Comparative study of flavonoids in experimental models of inflammation. Pharmacological Research, v. 48, p. 601-606, 2003. RUEFF, A.; DRAY, A. Sensitization of peripheral afferent fibres in the in vitro neonatal rat spinal cord by bradykinin and prostaglandins. Neuroscience, v. 54, p. 527-535, 1993. 74 SALAHDEEN, H. M.; YEMITAN, O. Neuropharmacological effects of aqueous leaf extract of Brophyllum pinnatum in mice. African Journal of Biomedical Research, v. 9, p. 101-107, 2006. SALEH, T. S. F, CALIXTO, J. B, MEDEIROS, Y. S. Effects of anti-inflammatory drugs upon nitrate and myeloperoxidase levels in the mouse pleurisy induced by carrageenan. Peptides, v. 20, n. 8, p. 949-956, 1999. SANTOS, A.L. Avaliação das ações analgésica e antiinflamatória das frações purificadas de duas espécies comuns de Tanchagem: Plantago major L e Plantago lanceolata L. 1998. Dissertação. São Paulo. SANZ, M.J.; KUBES, P. Neutrophil-active chemokines in in vivo imaging of neutrophil trafficking. European Journal of Immunology, v. 42, p. 278-283, 2012. SCHACHNA, L. The anti- TNF revolution in ankylosing spondylits. Medical Journal of Australia, Sydney, v. 181, n. 10, p. 529-530, 2004. SHAGHAGHI, M.; MANZOORI, J. L.; AFSHAR, D. J.; JOUYBAN, A. Determination of flavonoids in pharmaceutical preparations using Terbium sensitized fluorescence method. DARU, v. 17, p. 264-268, 2009. SCHAIBLE, H. G.; SCHMIDT, R. F. Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. Journal of Neurophysiology, v. 60, n. 6, p. 2180-2195, 1988. SCHULER, V.; SUTERA, K.; FÜRERA, K.; EBERLI, D.; HORST, M.; BETSCHART, C.; BRENNEISEN, R.; HAMGURGER, M.; MENNET, M.; SCHNELLE, M.; SIMÕESWÜST, A. P.; VON MANDACH, U. Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips - A pharmacological study towards a new treatment option of overactive bladder. Phytomedicine, v. 19, p. 947-951, 2012. SCHULTZ, J.; KAMINKER, K. Myeloperoxidase of the leucocyte of normal human blood. Archives of Biochemistry and Biophysics, v. 96, p. 465-467, 1962. SEWELL, R. D. E.; RAFIEIAN-KOPAEI, M. The history and ups and downs of herbal medicine usage. Journal of Herbal Medicine and Pharmacology, v. 3, p. 1-3, 2014. SGARBI, M. W. M; SILVA JUNIOR, B. A.; NETO, H.; SOARES, J. The importance of systemic inflammatory response (SIRS) in the prognosis of polytraumatized patients. Revista Brasileira de Ortopedia, v. 41, n. 2, p. 1-6, 2006. SHAIK, Y. B.; CASTELLANI, M. L.; PERRELLA, A. Role of quercetin (a natural herbal compound) in allergy and inflammation. Journal of Biological Regulators and Homeostatic agents, v. 20, p. 47-52, 2006. SHARMA, N. K.; PRIYANKA, K. K. Evaluation of Analgesic and Anti-Inflammatory Activity of Kalanchoe spanthulata Leaves Extract. Journal of Advanced Scientific Researchs, v. 2, n. 4, p. 71-73, 2011. 75 SHEERAN, P.; HALL, G. M. Cytokines in anaesthesia. British Journal of Anaesthesia, v. 78, p. 201-219, 1997. SHUKLA, A. B.; MANDAVIA, D. R.; BARVALIYA, M. J.; BAXI, S. N.; THIPATHI, C. R. Evaluation of anti-urolithiatic effect of aqueous extract of Bryophyllum pinnatum(Lam.) leaves using ethylene glycol-induced renal calculi. Avicenna Journal of Phytomedicine, v. 4, n. 3, p. 151-159, 2014. SIDDIQUI, S.; FAIZI, S.; SIDDIQUI, B. S.; SULTANA, N. Triterpenoids and phenanthrenes from leaves of Bryophyllum Pinnatum. Phytochemistry, v. 28, p. 2433-2438, 1989. SIMÃO DA SILVA, K. A. B.; PASZCUK, A. F.; PASSOS, G. F.; SILVA, E. S.; BENTO, A. F.; MEOTTI, F. C.; CALIXTO, F. B. Activation of cannabinoid receptors by the pentacyclic triterpene α,􀈕-amyrin inhibits inflammatory and neuropathic persistente pain in mice. Pain, v. 152, p. 1872-1887, 2011. SMITH, W. L.; DeWITT, D. L.; GARAVITO, R. M. Cyclooxygenases: structural, cellular, and molecular biology. Annual Review of Biochemistry, v. 69, p. 145-182, 2000. SOARES, D. M.; MACHADO, R. R.; YAMASHIRO, L. H.; MELO, M. C. C.; SOUZA, G. E. P. Cytokine-induced neutrophil chemoattractant (CINC)-1 induces fever by a prostaglandin-dependent mechanism in rats. Brain Research, v. 1233, p. 79-88, 2008. SOKAL, R. R.; ROHLF, F. J. Biometry: The principles and Practice of Statistics. New York: W. H. Freemann, 1981. p. 859. SOUSA, P. J. C.; ROCHA, J. C. S.; PESSOA, A. M.; ALVES, L. A.; CARVALHO, J. C. T. Estudo preliminar da atividade anti-inflamatória de Bryophillum calycinum Salisb. Revista Brasileira de Farmacognosia, v. 15, n. 1, p. 60-64, 2005. SPENCER, J. P. E.; VANZOUR, D.; RENDEIRO, C. Flavonoids and cognition: The molecular mechanisms underlying their behavioural effects. Archives of Biochemistry and Biophysics, v. 492, p. 1-9, 2009. SPINOSA, H. S.; GÓRNIAK, S. L.; BERNARDI, M. M. Farmacologia aplicada a Medicina Veterinária. 2011. 5ª ed. Rio de Janeiro: Guanabara Koogan. STEAGALL, P. V. M.; MOUTINHO, F. Q.; MATOVANI, F. B.; PASSARELLI, D.; THOMASSIAN, A. Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats. Research in Veterinary Science, v. 86, p. 115-120, 2009. STENKEN, J. A.; POSCHENRIEDER, A. J. Bioanalytical chemistry of cytokines: A review. Analytica Chimica Acta, v. 853, p. 95-115, 2015. SUMNER, J. The natural history of medicinal plants. Portland: Timber Press. 2000. 235p. 76 SUPRATMAN, U.; FUJITA, T.; AKIYAMA, K.; HAYASHI, H. Insecticidal compounds from Kalanchoe daigremontiana × tubiflora. Phytochemistry, v. 58, p. 311-314, 2001a. SUPRATMAN, U.; FUJITA, T.; AKIYAMA, K.; HAYASHI, H.; MURAKAMI, A.; SAKAI, H.; KOSHIMIZU, K.; OHIGASHI, H. Anti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora. Bioscience, Biotechnology, and Biochemistry, v. 65, p. 947-949, 2001b. SUTTON, S.; CLUTTERBUCK, A.; HARRIS, P.; GENT, T.; FREEMAN, S. FOSTER, N.; BARRET-JOLLEY, R.; MOBASHERI, A. The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis. The Veterinary Journal, v. 179, p. 10-24, 2009. TAIWO, O.; LEVINE, J. D. Prostaglandin effects after elimination of indirect hyperalgesic mechanisms in the skin of the rat. Brain Research, v. 492, p. 397-399, 1989. TAKANO-ISHIKAWA, Y.; GOTO, M.; YAMAKI, K. Structure activity relations of inhibitory effects of various flavonoids on lipopolysaccharide-induced prostaglandin E2 production in rat peritoneal macrophages: comparison between subclasses of flavonoids. Phytomedicine, v. 13, n. 5, p. 310-317, 2006. TAPAS, A. R.; SAKARKAR, D. M.; KAKDE, R. B. Flavonoids as nutraceuticals: A Review. Tropical Journal of Pharmaceutical Research, v. 7, p. 1089-1099, 2008. TARTAGLIA, L. A.; WEBER, R. F.; FIGARI, I. S.; REYNOLDS, C.; PALLADINO, M. A. JR, GOEDDEL, D. V. The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proceedings of the National Academy of Sciences of the U.S.A., v. 88, p. 9292-9296, 1991. THOMPSON, S. W. N.; DRAY, A.; URBAN, L. Injury-induced plasticity of spinal reflex activity: NK1 neurokinin receptor activation and enhanced A- and C-fiber mediated responses in the rat spinal cord in vitro. Journal of Neuroscience, v. 14, p. 3672-3687, 1994. TILLEY, S. L.; COFFMAN, T. M.; KOLLER, B. H. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. The Journal of Clinical Investigation, v. 108, p. 15-23, 2001. TORRES-SANTOS, E. C.; DA SILVA, S. A. G.; COSTA, S. S.; SANTOS, A. P. P. T.; ALMEIDA, A. P.; ROSSI-BERGMAN, B. Toxicological Analysis and Effectiveness of Oral Kalanchoe pinnata on a Human Case of Cutaneous Leishmaniasis. Phytotherapy Research, v. 17, p. 801-803, 2003. TRACEY, K. J.; CERAMI, A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annual Review Medicine, Palo Alto, v. 45, p. 491-503, 1994. TREVISAN, M. T. S.; BEZERRA, M. Z. B.; SANTIAGO, G. M. P.; FEITOSA, C. M.; VERPOORTE, R.; BRAZ, R. Larvicides and acetyl-cholinesterase inhibitors from Kalanchoe species. Quimica Nova, v. 29, p. 415-418, 2006. 77 TUBARO, A.; DRI, P.; MELATO, M.; MULAS, G.; BIANCHI, P.; DEL NEGRO, P.; DELLA LOGGIA, R. In the croton oil ear test the effects of non steroidal anti-inflammatory drug (NSAIDs) are dependent on the dose of the irritant. Agents Actions, v. 19, p. 371-373, 1986. TURK, D. C.; MELZACK, R. The measurement of pain and the assessment of people experiencing pain. In: D. C. Turk & R. Melzack (eds) Handbook of Pain assessment. 1992. Nova York, Guilford, p. 3-12. TYLER, V.E. Herbal medicine: from the past to the future. Public Health Nutrition, Wallingford, v. 3, n. 4A, p. 447-452, 2000. VACHER, P. J.; DUCHÉNE-MARULLAZ, P.; BARBOT, P. A propos de quelques produits usuels – comparaison de deux méthodes d’étude des analgésiques. Medicina Experimentalis, v. 11, p. 51-58, 1964. VAN WYK, B. E.; VAN OUDTSHOORN, B.; GERICKE, N. 1997. Medical Plants of South Africa, 1st ed. Briza publications, Pretoria. VANE, J. R. Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-like Drugs. Nature: New Biology, v. 231, p. 232-235, 1971. VANE, J. R.; BAKHLE, Y. S.; BOTTING, R. M. Cyclooxygenase 1 and 2. Annual Review of Pharmacology and Toxicology, v. 38, p. 97-120, 1998. VEIGA-JÚNIOR, V. F.; PINTO, A. C.; MACIEL, M. A. M. Plantas medicinais: cura segura? Química Nova, v. 28, p. 519-528, 2005. VERGNOLLE, N. Postinflammatory visceral sensitivity and pain mechanisms. Eurogastroenterology and Motility, v. 20, p. 73-80, 2008. VERPOORTE, R.; VAN DER HEIJDEN, R.; MEMELINK, J. Engineering the plant cell factory for secondary metabolite production. Transgenic Research, Dordrecht, v. 9, p. 323-343, 2000. VERRI JR, W. A.; CUNHA, T. M.; PARADA, C. A.; POOLE, F. Q. C.; FERREIRA, S. H. Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development? Pharmacology and Therapeutics, v. 112, p. 116-138, 2006. VIEGAS Jr, C.; BOLZANI, V. S.; BARREIRO, E. J. Os produtos naturais e a química medicinal moderna. Química Nova, v. 29, n. 2, p.326-337, 2006. VINEGAR, R.; TRUAX, J. F.; SELPH, J. L.; VOELKER, F. A. Pathway of onset, development, and decay of carrageenan pleurisy in the rat. Federation Proceedings, v. 41, p. 2588-2595, 1982. VINEGAR, R.; TRUAX, J. F.; SELPH, J. L. Quantitative studies of the pathway to acute carrageenin inflammation. Federation Proceedings, n. 35, p. 2447-2454, 1976. 78 WAAGE, A.; HALSTENSEN, A.; ESPEVIK, T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet, v. 1, n. 8529, p. 355-357, 1987. WALDMANN, R.; BASSILANA, F.; DE WEIL, J.; CHAMPIGNY, G.; HEURTEAUX, C.; LAZDUNSKI, M. Molecular cloning of a non-inactivating proton-gated Na channel specific for sensory neurons. The Journal of Biological Chemistry, v. 272, p. 20975-20978, 1997b. WALDMANN, R.; CHAMPIGNY, G.; BASSILANA, F.; HEURTEAUX, C.; LAZDUNSKI, M. A proton-gated cation channel involved in acid-sensing. Nature, v. 386, p. 173-177, 1997a. WALL, P.D. The laminar organization of dorsal horn and effects of descending impulses. Journal of Physiology, v. 188, n. 3, p. 403-423, 1967. WALTERS, E.T. Injury-related behavior and neuronal plasticity: An evolutionary perspective on sensitization, hyperalgesia and analgesia. Intetional Review of Neurobiology, v. 36, p. 325-427, 1994. WALTERS, E.T. A Functional, Cellular, and Evolutionary Model of Nociceptive Plasticity in Aplysia. Biological Bulletin, v. 180, n. 2, p. 241-251, 1991. WANG, J.; AL-LAMKI, R. S.; ZHANG, H.; KIRKILES-SMITH, N.; GAETA, M. L.; THIRU, S.; POBER, J. S.; BRADLEY, J. R. Histamine antagonizes tumor necrosis fator (TNF) signalling by stimulating TNF receptor shedding from the cell surface and Golgi storage pool. The Journal of Biological Chemistry, v. 278, n. 24, p. 21751-21760, 2003. WANG, Q. S.; YANG, L.; CUI, W. Y.; CHEN, L.; JIANG, Y. H. Anti-inflammatory and anti-nociceptive activities of methanol extract from aerial part of Phlomis younghusbandii Mukerjee. PLoS ONE, v. 9, n. 3, 2014. WHICHER, J. T.; EVANS, S. W. Cytokines in disease. Clinical Chemistry, v. 36, n. 7, p. 1269-1281, 1990. WILLIAMS, A. C. C. et al. Evaluation of a cognitive behavioural programme for rehabilitating patients with chronic pain. British Journal of General Practice, v. 43, p. 513- 518, 1993. WILLINGALE, H. L.; GARDINER, N. J.; McLYMONT, N.; GIBLET, S.; GRUBB, B. D. Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. British Journal of Pharmacology, v. 122, p. 1593-1604, 1997. WILLIS, W. D.; COGGESHALL, R.E. Sensory mechanisms of the spinal cord. 1991. New York: Plenum Press. WILLOUGHBY, D. A.; MOORE, A. R.; COLVILLE-NASH, P. R. COX-1, COX-2, and COX-3 and the future of chronic inflammatory disease. Lancet, v. 355, p. 646-648, 2000. 79 WOJDASIEWICZ, P.; PONIATOWSKI, L. A.; SZUKIEWICZ, D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators of Inflammation, v. 2014, p. 1-19, 2014. WONG, M. M.; FISH, E. N. Chemokines: Attractive mediators of the immune response. Seminars in Immunology, v. 15, p. 5-14, 2003. WOOLF, C. J.; ALLCHORNE, A.; SAFIEH-GARABEDIAN, B.; POOLE, S. Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumor necrosis factor alpha. British Journal Pharmacology, v. 121, p. 417-424, 1997. WOOLF, C. J.; MANNION, R. J. Neuropathic pain: etiology, symptoms, mechanisms, and management. Lancet, v. 353, p. 1959-1964, 1999. WRIGHT, A. Recent concepts in the neurophysiology of pain. Manual Therapy, v. 4, p. 196-202, 1999. WU, A. J.; JUA, H.; MUNSON, S. H.; McDEVITT, H. O. Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proceedings of the National Academy of Sciences of the U.S.A., v. 99, p. 12287-12292, 2002. YADAV, N. P.; DIXIT, V. K. Hepatoprotective activity of leaves of Kalanchoe pinnata Pers. Journal of Ethnopharmacology, v. 86, p. 197-202, 2003. YAMADA, C. S. B. Fitoterapia: sua história e importância. Revista Racine, São Paulo, v. 43, p. 50-51, 1998. YAMAGISHI, T.; HARUNA, M.; YAN X-Z; CHANG, J. J.; LEE, K. H. Antitumor Agents, 110. Bryophyllin B, a novel potent cytotoxic bufadienolide from Bryophyllum pinnatum. Journal of Nattural Products, v. 52, p. 1071-1079, 1989. YAO, L. H.; JIANG, Y. M.; SHI, J.; TOMÁS-BARBERÁN, F. A.; DATTA, N.; SINGANUSONG, R.; CHEN, S. S. Flavonoids in food and their health benefits. Plant Foods for Human Nutrition, v. 59, n. 3, p. 113-122, 2004. YUNES, R. A.; CECHINEL FILHO, V. Plantas medicinais sob a ótica da química medicinal moderna; Yunes, R. A.; Calixto, J. B., eds.; 1a ed.; Ed. Argos: Chapecó, 2001, cap. 1; Yunes, R. A.; Pedrosa, R. C.; Cechinel Filho, V.; Quim. Nova 2001, 24, 147. XU, X.; HAO, J.; ANDELL-SONSSON, S.; POLI, V.; BARTFAI, T.; WIESENFELDHALLIN, Z. Nociceptive responses in interleukin-6-deficient mice to peripheral inflammation and peripheral nerve section. Cytokine, v. 9, p. 1028-1033, 1997. XUE, Q.; LU, Y.; EISELE, M. R.; SULISTIJO, E.; FAN, R.; MILLER-JENSEN, K. Analysis of single-cell secretion reveals a role for paracrine signaling in coordinating macrophage response to TLR4 stimulation. Science Signaling, v. 8, n. 381, p. 1-12, 2015. YUAN, C.; SIDHU, R. S.; KUKLEV, D. V.; KADO, Y.; WADA, M.; SONG, I.; SMITH, W. L. Cyclooxygenase allosterism, fatty acid-mediated cross-talk between 80 monomers of cyclooxygenase homodimers. The Journal of Biological Chemistry, v. 284, p. 10046-10055, 2009. ZANINI JUNIOR, J. C.; MEDEIROS, Y. S.; CRUZ, A. B.; YUNES, R. A.; CALIXTO, J. B. Actions of compounds from Manderilla velutina on croton oil-induced ear edema in mice. A comparative study with steroidal and nonsteroidal antiinflammatory drugs. Phytotherapy Research, v. 6, p. 1-5, 1992. ZAKARIA, Z. A.; GOPALAN, H. K.; ZAINAL, H.; MOHD POJAN, N. H.; MORSID, N. A.; ARIS, A.; SULAIMAN, M. R. Antinociceptive, anti-inflammatory and antipyretic effects of Solanum nigrum chloroform extract in animal models. Yakugaku Zasshi, v. 126, n. 11, p. 1171-1178, 2006. ZIMMERMANN, M. Ethical considerations in relation to pain in animal experimentation. Acta Physiologica Scandinavica Supplement, v. 554, p. 221-233, 1986. ZIMMERMANN, M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain, v. 16, n. 2, p. 109-110, 1983. ZUURBIER, K. W; VAN DEN BERG, J. D.; VAN GELDER, B. F.; MUIJSERS, A. O. Human Hemi-myeloperoxidase. Initial chlorinating activity at neutral pH, compound II and III formation, and stability towards hypochlorous acid and high temperature. European Journal of Biochemistry, v. 205, p. 737-742, 1992.por
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