Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Ribeiro, Adyelle Dantas lattes
Orientador(a): Pereira, Jozinete Vieira lattes
Banca de defesa: Pereira, Jozinete Vieira lattes, Silva, Diego Romário lattes, Oliveira Filho, Abrahão Alves de lattes, Damasceno, Bolívar Ponciano Goulart de Lima lattes, Silva, Andrea Cristina Barbosa lattes
Tipo de documento: Tese
Tipo de acesso: Acesso embargado
Idioma: por
Instituição de defesa: Universidade Estadual da Paraíba
Programa de Pós-Graduação: Programa de Pós-Graduação em Odontologia - PPGO
Departamento: Pró-Reitoria de Pós-Graduação e Pesquisa - PRPGP
País: Brasil
Palavras-chave em Português:
Fitoterapia
Úlceras traumáticas
Mucosa oral
Área do conhecimento CNPq:
CIENCIAS DA SAUDE::ODONTOLOGIA
Link de acesso: http://tede.bc.uepb.edu.br/jspui/handle/tede/4722
Resumo: Traumatic ulcers (UTs) of the oral mucosa consist of a group of common changes in the oral cavity that cause painful symptoms and affect the well-being of the patient. The therapies available for the treatment of these injuries are isolated in terms of application and the occurrence of adverse effects. In this context, the search for new therapeutic alternatives from medicinal plants, such as limonene, a terpene with properties of pharmacological interest, stands out. This study evaluated in silico and in vitro, the antifungal activity of R-(+)-limonene isolated on Candida spp, and incorporated into an emulgel its physicochemical properties, antifungal, toxicological, anti-inflammatory and healing action of this emulgel. Through the in silico assay, the probability of the biological potential of the monoterpene, its theoretical oral bioavailability and acute oral toxicity were evaluated. The following strains were used: C. albicans ATCC 10231, C. glabrata ATCC 90031, C. krusei ATCC 6258, C. tropicalis ATCC 750, C. parapsilosis (ATCC 22019) and clinical isolates of C. albicans A1, and C. albicans A2. The Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC) was determined by microdilution, its effect on the growth kinetics of C. albicans and its antifungal potential by logarithmic reduction. The physical-chemical properties of the emulgel based on R-(+)-limonene (ELI) were determined by means of pH, resistance to centrifugation, accelerated centrifugation and spreadability. Acute oral toxicity and clastogenic and aneugenic potential were evaluated in Mus musculus mice (2000mg/kg). Wistar rats were submitted to the application of 5% acetic acid in the buccal mucosa to evaluate the anti-inflammatory and healing potential of the formulation, through clinical and histopathological analysis. Data were analyzed using descriptive and inferential statistics, analyzed using GraphPad Prism 5.0® software, San Diego, CA, USA. The in silico assays estimated that R-(+)-limonene has a broad spectrum of action on microorganisms of great clinical importance. The MIC of R-(+)-limonene ranged from 656.25 µg/mL to 2625 µg/mL and was classified as fungistatic on the C. albicans strain (ATCC 10231), while for the other species its action was fungicide. R-(+)-limonene had a potentially significant effect on the growth kinetics of C. albicans (p<0.05). The ELI showed an acidic pH of 5.71 ± 0.11; 5.71 ± 0.09 and 5.97 ± 0.05 for formulation of the emulgel with R-(+)-limonene (ELI) at 1.2%, 2.4% and 5%, respectively, and 5.74 ± 0.21 for the control formulation, good stability and spreadability, as well as good viscosity. Through analysis of growth kinetics and logarithmic reduction, it can be seen that the product significantly inhibited the growth of C. albicans in all the different concentrations tested when compared to the growth control. ELI did not induce signs of acute toxicity in mice submitted to gavage treatment at a single dose of 2000 mg/kg and produced a statistically significant lower number of micronuclei compared to the positive control (cyclophosphamide 50 mg/kg) in mouse erythrocytes. R-(+)-limonene has been shown to be a potential antifungal agent against Candida species, both as an isolated compound and incorporated into the emulgel. The ELI showed low toxicity and mutagenicity, in addition to good anti-inflammatory and healing action in the treatment of UTs in the oral cavity of Wistar rats. Therefore, the developed formulation was considered promising for the treatment of UTs in the oral cavity.
id UEPB_705f7bffc26fc8478b6888bea5dc8598
oai_identifier_str oai:tede.bc.uepb.edu.br:tede/4722
network_acronym_str UEPB
network_name_str Biblioteca Digital de Teses e Dissertações da UEPB
repository_id_str
spelling Pereira, Jozinete Vieirahttps://orcid.org/0000-0001-7225-6409http://lattes.cnpq.br/8041850574045487Damasceno, Bolívar Ponciano Goulart de Limahttps://orcid.org/0000-0002-0747-0297http://lattes.cnpq.br/6407334157973308Pereira, Jozinete Vieirahttps://orcid.org/0000-0001-7225-6409http://lattes.cnpq.br/8041850574045487Silva, Diego Romáriohttps://orcid.org/0000-0001-9724-0147http://lattes.cnpq.br/0522585351371155Oliveira Filho, Abrahão Alves dehttps://orcid.org/0000-0002-7466-9933http://lattes.cnpq.br/7440461731944347Damasceno, Bolívar Ponciano Goulart de Limahttps://orcid.org/0000-0002-0747-0297http://lattes.cnpq.br/6407334157973308Silva, Andrea Cristina Barbosahttps://orcid.org/0000-0001-8964-8919http://lattes.cnpq.br/5097978858569561https://orcid.org/0000-0001-8147-2592http://lattes.cnpq.br/3858737000492701Ribeiro, Adyelle Dantas2023-08-22T11:05:11Z2999-12-312023-07-31RIBEIRO, Adyelle Dantas. Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral. 2023. 111 f. Tese (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande, 2023.http://tede.bc.uepb.edu.br/jspui/handle/tede/4722Traumatic ulcers (UTs) of the oral mucosa consist of a group of common changes in the oral cavity that cause painful symptoms and affect the well-being of the patient. The therapies available for the treatment of these injuries are isolated in terms of application and the occurrence of adverse effects. In this context, the search for new therapeutic alternatives from medicinal plants, such as limonene, a terpene with properties of pharmacological interest, stands out. This study evaluated in silico and in vitro, the antifungal activity of R-(+)-limonene isolated on Candida spp, and incorporated into an emulgel its physicochemical properties, antifungal, toxicological, anti-inflammatory and healing action of this emulgel. Through the in silico assay, the probability of the biological potential of the monoterpene, its theoretical oral bioavailability and acute oral toxicity were evaluated. The following strains were used: C. albicans ATCC 10231, C. glabrata ATCC 90031, C. krusei ATCC 6258, C. tropicalis ATCC 750, C. parapsilosis (ATCC 22019) and clinical isolates of C. albicans A1, and C. albicans A2. The Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC) was determined by microdilution, its effect on the growth kinetics of C. albicans and its antifungal potential by logarithmic reduction. The physical-chemical properties of the emulgel based on R-(+)-limonene (ELI) were determined by means of pH, resistance to centrifugation, accelerated centrifugation and spreadability. Acute oral toxicity and clastogenic and aneugenic potential were evaluated in Mus musculus mice (2000mg/kg). Wistar rats were submitted to the application of 5% acetic acid in the buccal mucosa to evaluate the anti-inflammatory and healing potential of the formulation, through clinical and histopathological analysis. Data were analyzed using descriptive and inferential statistics, analyzed using GraphPad Prism 5.0® software, San Diego, CA, USA. The in silico assays estimated that R-(+)-limonene has a broad spectrum of action on microorganisms of great clinical importance. The MIC of R-(+)-limonene ranged from 656.25 µg/mL to 2625 µg/mL and was classified as fungistatic on the C. albicans strain (ATCC 10231), while for the other species its action was fungicide. R-(+)-limonene had a potentially significant effect on the growth kinetics of C. albicans (p<0.05). The ELI showed an acidic pH of 5.71 ± 0.11; 5.71 ± 0.09 and 5.97 ± 0.05 for formulation of the emulgel with R-(+)-limonene (ELI) at 1.2%, 2.4% and 5%, respectively, and 5.74 ± 0.21 for the control formulation, good stability and spreadability, as well as good viscosity. Through analysis of growth kinetics and logarithmic reduction, it can be seen that the product significantly inhibited the growth of C. albicans in all the different concentrations tested when compared to the growth control. ELI did not induce signs of acute toxicity in mice submitted to gavage treatment at a single dose of 2000 mg/kg and produced a statistically significant lower number of micronuclei compared to the positive control (cyclophosphamide 50 mg/kg) in mouse erythrocytes. R-(+)-limonene has been shown to be a potential antifungal agent against Candida species, both as an isolated compound and incorporated into the emulgel. The ELI showed low toxicity and mutagenicity, in addition to good anti-inflammatory and healing action in the treatment of UTs in the oral cavity of Wistar rats. Therefore, the developed formulation was considered promising for the treatment of UTs in the oral cavity.As úlceras traumáticas (UTs) da mucosa oral consistem em um grupo de alterações comuns na cavidade oral que provocam sintomatologia dolorosa e afetam o bem-estar do paciente acometido. As terapias disponíveis para o tratamento dessas lesões possuem limitações em relação a aplicação e ocorrência de efeitos adversos. Nesse contexto, destaca-se a busca de novas alternativas terapêuticas, provenientes de plantas medicinais, como o limoneno, um terpeno que apresenta propriedades de interesse farmacológico. Esse estudo avaliou in silico e in vitro, a atividade antifúngica do R-(+)-limoneno isolado sobre Candida spp, e incorporado a um emulgel suas propriedades físico-químicas, ação antifúngica, toxicológica, anti-inflamatória e cicatrizante deste emulgel. Por meio do ensaio in silico, foi avaliada a probabilidade do potencial biológico do monoterpeno, sua biodisponibilidade oral teórica e toxicidade oral aguda. Foram utilizadas as cepas: C. albicans ATCC 10231, C. glabrata ATCC 90031, C. krusei ATCC 6258, C. tropicalis ATCC 750, C. parapsilosis (ATCC 22019) e isolados clínicos de C. albicans A1, e C.albicans A2. Determinou-se a Concentração Inibitória Mínima (CIM), Concentração Fungicida Mínima (CFM) por microdiluição, seu efeito sobre a cinética de crescimento de C. albicans e o potencial antifúngico por redução logarítmica. As propriedades físico-químicas do emulgel à base de R-(+)-limoneno (ELI) foram determinadas por meio do pH, da resistência à centrifugação, viscosidade e espalhabilidade. A toxicidade oral aguda e o potencial clastogênico e aneugênico foram avaliados em camudongos Mus musculus (2000mg/kg). Ratos Wistar foram submetidos a aplicação de ácido acético a 5% em mucosa jugal para avaliar o potencial anti-inflamatório e cicatrizante da formulação, por meio de análise clínica e histopatólogica. Os dados foram analisados por estatística descritiva e inferencial, analisados através do software GraphPad Prism 5.0®, San Diego, CA, EUA. Os ensaios in silico estimaram que o R-(+)-limoneno apresenta um amplo espectro de ação sobre microrganismos de grande importância clínica. A CIM do R-(+)-limoneno variou na faixa de 656,25 µg/mL a 2625 µg/mL e se classificou como fungistático sobre a cepa de C. albicans (ATCC 10231), enquanto para as demais espécies sua ação foi fungicida. O R-(+)-limoneno apresentou potencial efeito significativo sobre a cinética de crescimento de C.albicans (p<0,05). O ELI apresentou pH de caráter ácido, de 5,71 ± 0,11; 5,71 ± 0,09 e 5,97 ± 0,05 para formulação do emulgel com R-(+)-limoneno (ELI) a 1,2%, 2,4% e 5%, respectivamente, e 5,74 ± 0,21 para a formulação controle, boa estabilidade e espalhabilidade, assim como boa viscosidade. Por meio das análises da cinética de crescimento e da redução logarítimica, pode-se constatar que o produto inibiu significativemente o crescimento de C.albicans em todas as diferentes concentrações testadas quando comparado ao controle de crescimento. O ELI não induziu sinais de toxicidade aguda nos camudongos submetidos ao tratamento por gavagem na dose única de 2000 mg/kg e produziu um menor número de micronúcleos estatisticamente significativo comparado ao controle positivo (ciclofosfomida a 50 mg/kg) em eritrócitos de camudongos. O R-(+)-limoneno demonstrou ser um potencial agente antifúngico contra espécies de Candida, tanto como composto isolado como incorporado ao emulgel. O ELI apresentou baixa toxicidade e mutagenicidade, além de uma boa ação anti-inflamatória e cicatrizante no tratamento de UTs na cavidade oral de ratos Wistar. Portanto, a formulação desenvolvida foi considerada promissora para o tratamento de UTs na cavidade oral.Submitted by Adyelle Ribeiro (adyelle.ribeiro@aluno.uepb.edu.br) on 2023-08-20T18:57:32Z No. of bitstreams: 2 TESE.pdf: 2804948 bytes, checksum: 1e5fce1976e9cb93fc59be3fbc25b169 (MD5) Termo de Depósito BDTD.pdf: 161528 bytes, checksum: fab0625b459776ae5c6d20d11d0915ac (MD5)Approved for entry into archive by Rosalvo Andrade (rosalvo_andrade@servidor.uepb.edu.br) on 2023-08-21T23:16:29Z (GMT) No. of bitstreams: 2 TESE.pdf: 2804948 bytes, checksum: 1e5fce1976e9cb93fc59be3fbc25b169 (MD5) Termo de Depósito BDTD.pdf: 161528 bytes, checksum: fab0625b459776ae5c6d20d11d0915ac (MD5)Made available in DSpace on 2023-08-22T11:05:11Z (GMT). No. of bitstreams: 2 TESE.pdf: 2804948 bytes, checksum: 1e5fce1976e9cb93fc59be3fbc25b169 (MD5) Termo de Depósito BDTD.pdf: 161528 bytes, checksum: fab0625b459776ae5c6d20d11d0915ac (MD5) Previous issue date: 2023-07-31application/pdfporUniversidade Estadual da ParaíbaPrograma de Pós-Graduação em Odontologia - PPGOUEPBBrasilPró-Reitoria de Pós-Graduação e Pesquisa - PRPGPABID, W. K.; ALYAA I. N. The efficacy of a new paste formulation as an alternative therapeutic agent for traum atic ulcers. Journal of Taibah University Medical Sciences, v.16, n.5, p.724–32, 2021. ADELI, E. The use of supercritical anti-solvent (SAS) technique for preparation of Irbesartan-Pluronic® F-127 nanoparticles to improve the drug dissolution. Powder Technology, v. 298, p. 65–72, 2016. AKGULLU, C. et al. Nebivolol to attenuate the effects of hyper- homocysteinaemia in rats. Atherosclerosis, v. 240, n. 1, p. 33e39-39, 2015. ALCOBA-FLÓREZ, J. et al. PCR protocol for specific identification of Candida nivariensis, a recently described pathogenic yeast. Journal of Clinical Microbiology, v. 43, n. 12, p. 6194–61946, dez. 2005. AMARAL, R.B. et al. A. Terapia de fotobiomodulação no tratamento das lesões orais da síndrome de Stevens-Johnson: relato de caso. Hurev, v.45, n.4, p.478–82, 2020. AMINI, R.; ASLE-ROUSTA, M.; AGHAZADEH, S. Hepatoprotective effect of limonene against chronic immobilization induced liver damage in rats. Naunyn-Schmiedeberg's Archives of Pharmacology, v. 393, p. 2053–2059, 2020. ANAND, V.; GULATI, M.; GOVILA, V.; ANAND, B. Low level laser therapy in the treatment of aphthous ulcer. Indian Journal of Dental Research, v.24, n.2, p.267-70, 2013. ANDISHEH-TADBIR, A. et al. The effect of indocyanine green-mediated photodynamic therapy in healing of experimentally induced oral mucosal traumatic ulcer in rat. Lasers in Medical Science, v.36, n.3, p.611-618, 2021. ANDRADE-JORGE, E. et al. Novel synthesis of isoindoline/isoindoline-1, 3-dione derivatives under solventless conditions and evaluation with the human D 2 receptor. Medicinal Chemistry Research. v. 26, n. 10, p. 2420-2431, 2017. ANVISA. Guia para a condução de estudos não clínicos de toxicologia e segurança farmacológica necessários ao desenvolvimento de medicamentos. Versão 2, p. 1–48, 2019. ANVISA. Guia de estudos de estabilidade. Versão 1, p. 1-47, 2019. APTE, R. N. et al. Effects of micro-environment-and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour–host interactions. European journal of cancer, v. 42, n. 6, p. 751-759, 2006. ARAÚJO, G.M.F. et al. Nanoemulsions Loaded with Amphotericin B: Development, Characterization and Leishmanicidal Activity. Curr Pharm Des, v. 25, n. 14, p. 1616-1622, 2019. ARAÚJO-FILHO, H.G. et al. D-limonene exhibits superior antihyperalgesic effects in a β-Cyclodextrincomplexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice. Neuroscience, v.358, p.158-169, 2017. AYUNINGTYAS, N.F. et al. Expression of VEGF and CD-31 in traumatic ulcer of diabetic Wistar rats after application of Citrus limon peel essential oil. Journal of Oral Biology and Craniofacial Research, v. 13, p. 380–385, 2023. BADEE, A.Z.M.; HELMY, S.A.; MORSY, N.F.S. Utilisation of orange peel in the production of a-terpineol by Penicillium digitatum (NRRL 1202). Food Chemistry, v.126, p.849–854, 2011. BALKWILL, F.; MANTOVANI, A. Cancer and inflammation: implications for pharmacology and therapeutics. Clinical Pharmacology & Therapeutics, v. 87, n. 4, p. 401-406, 2010. BARROSA, D.B. et al. Antifungal activity of terpenes isolated from the Brazilian Caatinga: a review. Brazilian Journal of Biology, v. 83, e. 270966, p. 1-9, 2023. BERCZI, I.; SZENTIVANYI, A. Cytokines and chemokines. In I. Berczi & A. Szentivanyi (Eds.), NeuroImmune Biology, v. 3, p. 191-220: Elsevier, 2003. BERKOW, E. L.; LOCKHART, S. R. Fluconazole resistance in Candida species: a current perspective. Infection and drug resistance, v. 10, p. 237, 2017. BHATTARAI, N.; GUNN, J.; ZHANG, M. Chitosan-based hydrogels for controlled, localized drug delivery. Advanced Drug Delivery Reviews, v. 62, n. 1, p. 83-99, 2010. BIESKI, I.G.C. et al. Potencial econômico e terapêutico dos óleos essenciais mais utilizados no Brasil. Revista Fitos, v. 15, n. 1, p. 125-137, 2022. Biolab Farmacêutica Ltda: São Paulo – Ad-Muc [citado 2022 mar 01]. Disponível em: https://consultaremedios.com.br/ad-muc/bula. BIZZO, H.R.; REZENDE, C.M. O Mercado de óleos essenciais no brasil e no mundo na última década. Quim. Nova, v. 45, n. 8, p. 949-958, 2022. BOGDAN, C.; RÖLLINGHOFF, M.; DIEFENBACH, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Current Opinion in Immunology, v. 12, n. 1, p. 64-76, 2000. BOONLAI, W. et al. The effect of the preservative methylparaben on the thermoresponsive gelation behavior of aqueous solutions of poloxamer 407. Journal of Molecular Liquids, v. 240, p. 622–629, 2017. BRASIL. Resolução RDC n0 48, de 16 de março de 2004. Dispõe sobre o registro de medicamentos fitoterápicos. Diário Oficial da União, p. 7, 2004. CANTÓN, R. et al. IRT and CMT β-lactamases and inhibitor resistance. Clinical Microbiology and Infection, v. 14, n. SUPPL. 1, p. 53–62, 2008. CARVALHO, P.A.G.; PEREIRA-JÚNIOR, A.J.A.; NEGREIROS, W.A. Avaliação da dor causada pela mucosite oral em pacientes oncológicos. Rev Dor. v.10, n.1, p.47-50, 2009. CASTEL, B.M.M. et al. As bases farmacológicas dos cuidados farmacêuticos: o caso dos AINEs. Acta Farmacêutica Portuguesa, v. 2, n. 2, p. 79-87, 2013. CAVALCANTE, G. M. et al. Experimental model of traumatic ulcer in the cheek mucosa of rats. Acta Cirúrgica Brasileira, v.26, p.227-234, 2011. CAVALCANTI, J.M. et al. The essential oil of Croton zehntneri and trans-anethole improves cutaneous wound healing. J. Ethnopharmacol, v.144, p.240–247, 2012. CENSI, R. et al. Hydrogels for protein delivery in tissue engineering. Journal of Controlled Release, v. 161, n. 2, p. 680–692, 2012. CHARYULU, N.P. et al. Emulgel: A boon for enhanced topical drug delivery. J Young Pharm, v. 13, n.1, p.76-79, 2021. CHENG, T. L. et al. Plasminogen/thrombomodulin signaling enhances VEGF expression to promote cutaneous wound healing. Journal of Molecular Medicine, v.96, n.12, p.1333-1344, 2018. CHI, G. et al. Suppression of MAPK and NF-κB pathways by limonene contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury. Inflammation, v. 36, n. 2, p. 501–511, 2013. CHIU, Y-H. et al. “Radiation-Induced swallowing dysfunction in patients with head and neck cancer: a literature review.” Journal of the Formosan Medical Association, 2021. CHO, K.S. et al. “Terpenes from forests and human health.” Toxicological Research, v. 33, p. 97-106, 2017. CIRIMINNA, R. et al. Limonene: A versatile chemical of the bioeconomy. Chemical Communications, v. 50, n. 97, p. 15288–15296, 2014. CLEELAND, R.; SQUIRES, E. Evalution of new antimicrobials in vitro and in experimental animal infections. In: Lorian, V. M. D. Antibiotics in Laboratory Medicine. New York: Willians; Wilkins, p. 739-788, 1991. CLEVELAND, A. A. et al. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: results from population-based surveillance. PloS one, v. 10, n. 3, p. e0120452, 2015. CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard NCCLS document M27- A3. Wayne, PA, 2008. Code of Federal Regulations (CFR), 40, 141, 261, 268.40, Office of the federal register, national archives and records administration. US Government Printing Office, Superintendent of Documents, Washington, DC. 2018. CORDELLA, C. et al. Use of differential scanning calorimetry (DSC) as a new technique for detection of adultertion in honeys. 1. Study of adulteration effect on honey thermal behavior. J Agric Food Chem; v. 203, p. 208-250, 2002. COSTA, M.R.C. et al. Aplicação da fotobiomodulação laser em úlceras traumáticas na cavidade oral: revisão integrativa da literatura. International Journal of Science Dentistry, v.2, n.61, p. 145-161, 2023. CUI, R.Z.; BRUCE, A.J.; ROGERS, R.S. Recurrent apthous stomatitis. Clin Dermatol, v.34, n.4, p.475-481, 2016. DAMY, S.B. et al. Aspectos fundamentais da experimentação animal - aplicações em cirurgia experimental. Revista da Associação Médica Brasileira, v. 56, n. 1, p. 103–111, 2010. DANTAS, M. G. B. et al. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Scientific World Journal, v. 2016, 2016. DA SILVA, M.R.; OLIVEIRA, R.G. Avaliação do efeito carcinogênico e anticarcinogênico do levonorgestrel através do teste de detecção de clones de tumores epiteliais em células de Drosophila melanogaster. Revista Perquirere. v. 14, n.1, p. 200-217, 2017. DASSOLER, M. et al. Perfil fitoquímico e ensaio farmacológico de Averrhoa carambola L. (Oxalidaceae). J. Bras. Fitom, v.2, p.4–8, 2004. D'ALESSIO, P.A., et al. Oral administration of d-limonene controls inflammation in rat colitis and displays antiinflammatory properties as diet supplementation in humans. Life Sciences, n.10, p. 24-26, 2013. D'ALESSIO, P.A., et al. Skin Repair Properties of d-Limonene and Perillyl Alcohol in Murine Models. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, v.13, p.29-35, 2014. D´ARRIGO, M. et al. In vitro evaluation of the activity of an essential oil from Pistacia vera L. variety Bronte hull against Candida sp. BMC Complementary and Alternative Medicine, v. 19, n. 6, p. 1-7, 2019. DE ALMEIDA, A.A.C. et al. Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide. Inflammation, v. 40, n. 2, p. 511–522, 2017. DE SOUZA, M. C. et al. Gastroprotective effect of limonene in rats: Influence on oxidative stress, inflammation and gene expression. Phytomedicine, v. 53, p. 37–42, 2019. DJEKIC, L.; ČALIJA, B.; MEDAREVIĆ, Đ. Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug. Journal of Molecular Liquids, v. 303, p. 112639, 2020. DEMYTTENAERE, J.; KIMPE, N.; Biotransformation of terpenes by fungi: Study of the pathways involved. Journal of Molecular Catalysis B: Enzymatic, v. 11, n. 4-6, p. 265-270, 2011. DEWAN, M. et al. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations. International Journal of Biological Macromolecules, v. 72, p. 706–710, 2015. DO AMARAL, J.F., et al. Antinociceptive effect of the monoterpene R-(+)-limonene in mice. Biological and Pharmaceutical Bulletin, n. 30, p. 1217-20, 2007. DOMARADZKA, D.; GUZIK, U.; WOJCIESZYŃSKA, D. Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs. Reviews in Environmental Science and Bio/Technology. v. 14, n. 2, p. 229-239, 2015. DOUGHARI, J.H.; BAZZA, M.J. Phytochemistry, GC-ms analysis, antioxidant and antibacterial potentials of limonene isolated from pericarp of Citrus sinensis. International Journal of Microbiology and Biotechnology, v. 5, n. 1, p. 22, 2020. EDWARDS, R.; HARDING, K.G. Bacteria and wound healing. Curr Opin Infect Dis, v.17, n.2, p.91-96, 2004. ELAD, S. et al. Topical immunomodulators for management of oral mucosal conditions, a systematic review; Part II: miscellaneous agents. Expert opinion on emerging drugs, [S. l.], v.16, n.1, p.183–202, 2011. EMING, S. A.; WYNN, T. A.; MARTIN, P. Inflammation and metabolism in tissue repair and regeneration. Science, v. 356, n. 6342, 1026–1030, 2017. ENOCH, S.; LEAPER, D.J. Basic science of wound healing. Surgery (Oxford), v.23, n.2, p.37-42, 2005. ERASTO, P.; VILJOEN, A.M. Limonene - A review: biosynthetic, ecological and pharmacological relevance. Natural Produts Communications, v.3, n.7, p.1193-1202, 2008. FALCÃO, H. et al. Review of the plants with anti-inflammatory activity studied in Brazil. Braz. J. Pharmacogn., v.15, p.381–391, 2005. FARAH, C.; LYNCH, N.; MCCULLOUGH, M. Oral fungal infections: an update for the general practitioner. Australian Dental Journal, v. 55, p. 48–54, jun. 2010. FELIPE, L.O.; BICAS, J.L. Terpenos, aromas e química dos compostos naturais. Química Nova na Escola, v. 39, n. 2, p. 120-130, 2017. FERNANDES, N.D.L., et al. Lesões erosivas e ulcerativas da mucosa oral: uma revisão da literatura. Research, Society and Development, v. 11, n. 9, e20411931702, 2022. FERRERO-MILIANI, L. et al. Inflamação crônica: Importância de NOD2 e NALP3 na geração de interleucina-1beta. Clin. Exp. imunol. v. 147, p.227–235, 2007. FINFTER, O. et al. Photobiomodulation (low-level laser) therapy for immediate pain relief of persistent oral ulcers in chronic graft-versus-host disease. SupportCareCancer, v.29, n.8, p.4529–4534, 2021. FITZGERALD, K. A. et al. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature, v. 413, n. 6851, p. 78, 2001. FITZPATRICK, S.G.; COHEN D.M.; CLARK, A.N. Ulcerated lesions of the oral mucosa: clinical and histologic review. Head and Neck Pathology, v.13, n.1, p.91-102, 2019. FRANCE K.; VILLA, A. Acute oral lesions. Dermatol Clin, v. 38,4p. 41-450, 2020. FUJISAWA, K.; MIYAMOTO, Y.; NAGAYAMA, M. Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa. Journal of Oral Pathology and Medicine, v. 32, n. 6, p. 358–366, 2003. GALLEGOS-FLORES, P.I. et al. Actividad antibacteriana de cinco compuestos terpenoides: carvacrol, limoneno, linalool, α-terpineno y timol. Tropical and Subtropical Agroecosystems, v. 22, p. 241–248, 2019. GASMI, B.A. et al. Oral aphthous: pathophysiology, clinical aspects and medical treatment. Archives of Razi Institute, v.76, n.5, p.1155-1163, 2021. GILMORE, T. D. Introduction to NF-κB: players, pathways, perspectives. Oncogene, v. 25, n. 51, p. 6680, 2006. GIULIANO, E. et al. Mucosal applications of poloxamer 407-based hydrogels: an overview. Pharmaceutics, v.10, n.3, p.159, 2018. GOMEZ, A.; NELSON, K.E. The oral microbiome of children: development, disease, and implications beyond oral health. Microb Ecol 2016. Sep 14. [Epub ahead of print]. GOMES, N. M. L. et al. Fitoterapia como opção de tratamento para a mucosite oral. Archives of Health Investigation, v. 10, n. 1, p. 11–17, 2021. GONZALEZ, A.C.D.O. et al. Wound healing - A literature review. Anais brasileiros de dermatologia, v.91, p.614-620, 2016. GONZÁLEZ ROMA, L. B. Ulceración por trauma crónico: una lesión simuladora. Informe de un caso clínico. Rev. Asoc. Odontol, v.108, n.2, p. 57-62, 2020. GUIMARÃES, I.N.O.; ANDRADE, L.G. Atuação farmacêutica frente ao uso indiscriminado de antiinflamatórios não esteroidais (aines) por hipertensos. Revista Ibero-Americana de Humanidades, Ciências e Educação. São Paulo, v.8, n. 4, 2022. GUIMARÃES, M.A.; MÁZARO, T. Princípios éticos e práticos do uso de animais de experimentação. São Paulo: Universidade Federal de São Paulo, 2004. GUNAL, M.Y.; HEPER, A.O.; ZALOGLU, N. The effects of topical carvacrol application on wound healing process in male rats. Pharmacogn. J, v.6, p.10–14, 2014. HANSEN, J.S.; et al. Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice. Journal of Immunotoxicology, v.13, n.6, p.793-803, 2016. HARPER, R.S., et al. Acid-induced demineralisation of human enamel as a function of time and pH observed using X-ray and polarised light imaging. Acta Biomater. v. 15, n.120, p.240-248, 2021. HAYASHI, M. et al. Ensaio de micronúcleo de eritrócitos de roedores in vivo. Mutation Research, v. 312, p. 293–304, 1994. HEINRICH, P. C. et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochemical Journal, v. 374(Pt 1), 2003. HIROTA, R. et al. Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinae-treated mice. Inhalation Toxicology, v. 24, n. 6, p. 373–381, 2012. HOOD, K. A. et al. Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule-stabilizing activity. Cancer Research, v. 62, n. 12, p. 3356–3360, 2002. HUANG, H. et al. Thermo-sensitive hydrogels for delivering biotherapeutic molecules: A review. Saudi Pharmaceutical Journal, v. 27, n. 7, p. 990–999, 2019. HUANG, X. L. et al. Anti-inflammatory and antinociceptive effects of active ingredients in the essential oils from Gynura procumbens, a traditional medicine and a new and popular food material. Journal of Ethnopharmacology, v. 239, n. January, p. 111916, 2019. JONGEDIJK, E. et al. Biotechnological production of limonene in microorganisms. Applied Microbiology and Biotechnology, v. 100, n. 7, p. 2927–2938, 2016. KAIMOTO, T.; et al. Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene. European Journal of Pain, v.20, n.7, p.1155-1165, 2016. KAPUGI, M.; CUNNINGHAM, K. Corticosteroids. Orthopedic nursing, [S. l.], v.38, n.5, p.336–339, 2019. KARODI, R. et al. Evaluation of the wound healing activity of a crude extract of Rubia cordifolia L. (Indianmadder) in mice. Int. J.Appl. Res. Nat. Prod, v.2, p.12–18, 2009. KARPINSKI, T.M. Essential oils of lamiaceae family plants as antifungals. Biomolecules, v. 10, n. 103, 2020. KENNEDY, A. D.; DELEO, F. R. Neutrophil apoptosis and the resolution of infection. Immunologic Research, v. 43, n. 1-3, p. 25-61, 2009. KESKIN, I. et al. Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on experimental wound healing, Biotechnic & Histochemistry, v.92, n.4, p.274-282, 2017. KIEL, M.; ENGESSER, K.H. The biodegradation vs. biotransformation of fluorosubstituted aromatics. Applied microbiology and biotechnology. v. 99, n. 18, p. 7433-64, 2015. KIM, Y.W. et al. Safety evaluation and risk assessment of d-Limonene. Journal of Toxicology and Environmental Health, v.16, n.1, p.17-38, 2013. KLEPSER, M.E. et al. Influence of test conditions on antifungal time-kill curve results: Proposal for standardized methods. Antimicrobial Agents and Chemotherapy, v. 42, n. 5, p. 1207–1212, 1998. KOBAYASHI, S. D.; DELEO, F. R. Towards a comprehensive understanding of the role of neutrophils in innate immunity: a systems biology-level approach. Wiley Interdiscip. Rev. Syst. Biol. Med., v. 1, n. 3, p. 309-333, 2009. KOH, T. J.; DIPIETRO, L. A. Inflammation and wound healing: the role of the macrophage. Expert reviews in molecular medicine, v.13, 2011. KONG, E. F. et al. Development and in vivo evaluation of a novel histatin-5 bioadhesive hydrogel formulation against oral candidiasis. Antimicrobial agents and chemotherapy, v. 60, n. 2, p. 881-889, 2015. KOZLOVSKY, A. et al. Effect of local antimicrobial agents on excisional palatal wound healing: a clinical and histomorphometric study in rats. J Clin Periodontol, v. 34, n.2, p.164-71, 2007. KUMMER, R. et al. Evaluation of anti-inflammatory activity of citrus latifolia Tanaka essential oil and limonene in experimental mouse models. Evidence- based Complementary and Alternative Medicine, v. 2013, 2013. KUROIWA, Y. et al. Nano-scale and molecular-level understanding of wet-milled indomethacin/poloxamer 407 nanosuspension with TEM, suspended-state NMR, and Raman measurements. International Journal of Pharmaceutics, v. 537, n. 1–2, p. 30– 39, 2018. LAMBI, J.N. et al. Synthesis, spectral properties and thermal behaviour of zinc(II) acetylsalicylate. Thermochim Acta, v. 398, n.1-2, p. 145-51, 2003. LAPPAS, C.M.; LAPPAS, N.T. D-Limonene modulates T lymphocyte activity and viability. Cellular Immunology, v. 279, n.1, p.30-41, 2012. LEÃO, D.A. Caracterização e avaliação da toxicidade da berberina encapsulada com poloxamer 407 em Drosophila Melanogaster. 2021. 86f. Dissertação. (Mestrado em Tecnologia em Alimentos) - Universidade Tecnológica do Paraná, Campo Mourão, 2021. LEITE-ANDRADE, M.C. et al. Antifungal effect and inhibition of the virulence mechanism of D-Limonene against Candida parapsilosis. Molecules, v. 27, n. 8884, 2022. LEITE, P. M.; CAMARGOS, L. M.; CASTILHO, R. O. Recent progess in phytotherapy: a brazilian perspective. European Journal of Integrative Medicine, v. 41, p. 101270, 2020. LEMES, R. S. et al. Chemical composition and antibacterial activity of essential oils from Citrus aurantifolia leaves and fruit peel against oral pathogenic Bactéria. Annals of the Brazilian Academy of Sciences, v. 90, n. 2, p. 1285- 1292, 2018. LI, P.H.; CHIANG, B.H. Process optimization and stability of D-limonene-in water nanoemulsions prepared by ultrasonic emulsification using response surface methodology. Ultrasonics Sonochemistry, v.19, p.192–197, 2012. LI, W. et al. “Prevalence of dental erosion among people with gastroesophageal reflux disease in China.” The Journal of Prosthetic Dentistry, v.117, n.1, p.48–54, 2017. LI, X. et al. In silico prediction of chemical acute oral toxicity using multi-classification methods. Journal of chemical information and modeling.v. 54, n. 4, p. 1061-1069, 2014. LIMA, A.A.S.D.; GRÉGIO, A.M.T.; TANAKA, O.; MACHADO, M.Â.N.; FRANÇA, B.H.S. Tratamento das ulcerações traumáticas bucais causadas por aparelhos ortodônticos. Revista Dental Press de Ortodontia e Ortopedia Facial, v.10, p.30-36, 2005. LIMA DF, et al. Antinociceptive activity of the monoterpene alpha-phellandrene in rodents: possible mechanisms of action. Journal of Pharmacy and Pharmacology, v. 64, n.2, p. 283–92, 2012. LIU, Y. et al. Inhibitory efects of citrus lemon oil and limonene on Streptococcus sobrinus - Induced Dental Caries in Rats. Archives of Oral Biology, v. 118, p. 1-6, 2020. LOKE, C. et al. Factors affecting intra-oral pH - a review. Journal of oral rehabilitation, v.43, n.10, p.778–785, 2016. MAMEDE, L.C. et al. Comportamento térmico de alguns fármacos e medicamentos. Rev. Ciênc. Farm. Básica Apl., v. 27, n.2, p.151-155, 2006. MANDELBAUM, S.H. et al./ done at the Dermatology Service of the Teaching Hospital of Taubate, Dermatology course, MANDELBAUM, DI SANTIS & MANDELBAUM 393 An bras Dermatol. [S. l.], v. 78, n. 4, p. 393–410, 2003. MANSANO-SCHLOSSER, T.C.; CEOLIM, M.F. Qualidade de vida de pacientes com câncer no período de quimioterapia. Enfermagem, v.21, n.3, p.600-607, 2012. MARIANO, R.C.et al. Effect of topical application of chlorhexidine and metronidazole on the tissue repair of palatal wounds of rats: a clinical and histomorphometric study. Oral Surg Oral Med Oral Pathol Oral Radiol, v.119, n.5, p.505-513, 2015. MARÓSTICA, M. R.; PASTORE, G. M. Biotransformação de limoneno: Uma revisão das principais rotas metabólicas. Quimica Nova, v. 30, n. 2, p. 382– 387, 2007. MATOS, J.R.; MERCURI, L.; BARROS, G. Análise térmica aplicada a fármacos e medicamentos. In: STORPIRTIS, S. et al. Biofarmacocinética. Rio de Janeiro: Guanabara Koogan, 2009. cap. 4. p. 32-65. MAZZO, J. S O. et al. Desenvolvimento farmacotécnico de formulações de fotoprotetores FPS 30 e avaliação da estabilidade preliminar. Brazilian Journal of Development. v. 6, n. 8, p. 63696-63711, 2020. MEERAN, M.F.N. et al. O limoneno pode ser um possível candidato para avaliação como agente ou adjuvante contra infecção, imunidade e inflamação no COVID-19? Heliyon, v. 6, e05703, 2020. MELLO, G.D.; DANTAS, J.P.S.; BORGES, L.L. Busca in silico de moléculas com potencial antitumoral a partir da espécie Aloysia citriodora. Revista Brasileira Militar de Ciências, v. 7, n. 17, 2021. MELO et al., Cicatricial effect of Libidibia ferrea L. orabase formulation on traumatic ulcers oral in rats. Concilium, v.23, n.3, p.357-371, 2023. MIA, M. M.; BANK, R. A. The pro-fibrotic properties of transforming growth factor on human fibroblasts are counteracted by caffeic acid by inhibiting myofibroblast formation and collagen synthesis. Cell and Tissue Research, v.363, n.3, p.775-789, 2016. MIGUEL, M.G. “Antioxidant and anti-inflammatory activities of essential oils: a short review.” Molecules, v. 15, p. 9252-9287, 2010. MILLAN, J.; RIDLEY, A.J.; Rho GTPases and leucocyte-induced endothelial remodeling. Biochem. J., v.385, p.329-337, 2005. MILLSOP, J.W.; FAZEL, N. Oral candidiasis. Clinics in Dermatology, v. 34, n. 4, p. 487–494, jul. 2016. MIRANDA-CADENA, K. et al. Prevalence and antifungal susceptibility profiles of Candida glabrata, Candida parapsilosis and their close-related species in oral candidiasis. Archives of Oral Biology, v. 95, p. 100–107, nov. 2018. MITROPOULOU, G. et al. Citrus medica essential oil exhibits significant antimicrobial and antiproliferative activity. LWT - Food Science and Technology, v. 84, p. 344–352, 2017. MORAES, T. M. et al. Healing actions of essential oils from Citrus Aurantium and d-limonene in the Gastric Mucosa: The roles of VEGF, PCNA, and COX-2 in cell proliferation. Journal of Medicinal Food, v. 16, n. 12, p. 1162–1167, 2013. MORAIS, L.A.S. Influência dos fatores abióticos na composição química dos óleos essenciais. Horticultura Brasileira, v. 27, p. 4050- 4063, 2009. MOSVIN, C.V.; BUYLIN, B.A. Foundations of Laser Therapy. Triada Moskow, v.256, 2006. MOURA, A.B.R. et al. Candidíase pseudomembranosa em crianças com idade pré-escolar: uma breve revisão de literatura. Brazilian Journal of Surgery and Clinical Research - BJSCR, v. 26, n. 2, p. 80–84, 2019. MUNOZ, J.E. et al. In Vitro and In Vivo inhibitory activity of limonene against diferent isolates of Candida spp. J. Fungi, v. 6, n. 183, 2020. MUTHUKUMAR, T. et al. Effect of growth factors and pro-inflammatory cytokines by the collagen biocomposite dressing material containing Macrotyloma uniflorum plant extract-in vivo wound healing. Colloids and Surfaces B: Biointerfaces, v.121, p.178-188, 2014. NASCIMENTO, M. H. M. et al. Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release. International Journal of Biological Macromolecules, v. 111, p. 1245–1254, 2018. NIE, S. et al. Thermoreversible pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: In vitro drug release, cell cytotoxicity, and uptake studies. International Journal of Nanomedicine, v. 6, n. 1, p. 151–166, 2011. NOMURA E.C. et al. Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice. Journal of Ethnopharmacology, v. 150, n.2, p.583-589, 2013. OCDE. Diretrizes da OCDE para teste de produtos químicos. n. 19, p. 1–22, 2001 OLIVEIRA, B.V. et al. TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats. J Appl Oral Sci, v. 24, n. 3, p. 278-290, 2016. OLIVEIRA, M. A. et al. Análise térmica aplicada a fármacos e formulações farmacêuticas na indústria farmacêutica. Quim. Nova, v. 34, n. 7, p.1224-1230, 2011. OLIVEIRA, M.L. et al. Topical continuous use of Lippia sidoides Cham essential oil induces cutaneous inflammatory response, but does not delay wound healing process. J. Ethnopharmacol, v.153, p.283–289, 2014. OLIVEIRA, M.M.C. et al. O Uso Crônico de anti-inflamatórios não-esteroidais e seus efeitos adversos. Revista Caderno de Medicina, v. 2, n. 2, 2019. OMRAN, S. M. et al. The effects of limonene and orange peel extracts on some spoilage fungi. International Journal of Molecular and Clinical Microbiology, v. 1, p. 82-86, 2011. PARAMASHIVAM, S.K. et al. In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases. Bioinformation.v. 11, n. 2, n. 73, 2015. PARK, H.M. et al. Limonene, a natural cyclic terpene, is an agonistic ligant for adenosine A (2A) receptors. Biochemical and Biophysical Research Communications, n. 404, p. 345-348, 2011. PAULO FILHO, W.; RIBEIRO, J.E.; PINTO, D.S. Safety and efficacy of Eupatorium laevigatum paste as therapy for buccal aphthae: randomized, double-blind comparison with triamcinolone 0.1% orabase. Advances in therapy, v.32, n.4, p.375-378, jul. 2000. PEREIRA, G. C. et al. Avaliação da estabilidade de um xampu produzido com adição de óleo essencial de alecrim (Rosmarinus officinalis). Revista Teccen. v. 13, n.1, p. 02-07, 2020. PETERSON, D.E.; BENSADOUN, R. J.; ROILA, F. Management of oral and gastrointestinal mucositis: ESMO clinical practice guidelines. Annals of Oncology, v. 22, n. SUPPL. 6, p. 78–84, 2011. PINTO, E. et al. Antifungal activity of Thapsia villosa essential oil against Candida, Cryptococcus, Malassezia, Aspergillus and Dermatophyte Species. Molecules, v. 22, p. 1-11, 2017. PINTO, E. et al. Antifungal activity of Ferulago capillaris essential oil against Candida, Cryptococcus, Aspergillus and dermatophyte species. Eur J Clin Microbiol Infect Dis, v. 32, p. 1311–1320, 2013. PIRES JUNIOR, H. B. Efeitos toxicológicos agudos de estrato de frutos verdes de Meliaazedarach (MELIACEAE) em ratos (Rattusnovergiucus), camundongos (Musmusculares) e Artemia salina. 2010. 70f. Dissertação. (Mestrado em Ciência Animal) - Escola de Veterinária, Universidade Federal de Goiás, Goiânia, 2010. PORTOU, M. J. et al. The innate immune system, toll-like receptors and dermal wound healing: a review. Vascular pharmacology, v.71, p.31-36, 2015. PULITO, C. et al. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res, v. 39, n. 1, p. 210, 2020. PUSPASARI, A. et al. Effects of topical application of propolis extract on fibroblast growth factor-2 and fibroblast expression in the traumatic ulcers of diabetic Rattus norvegicus. J Oral Maxillofac Pathol., v.22, n.1, p.54-58, 2018. REHMAN, M.U., et al. D-limonene suppresses doxorubicininduced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats. Experimental Biology and Medicine, n.239, p. 465-476, 2014. RENNICK, L.A. et al. Effectiveness of a novel topical powder on the treatment of traumatic oral ulcers in orthodontic patients: A randomized controlled trial. AngleOrthod, v.86, n.3, p.351–357, 2016. RIBEIRO, T.E.; MARANGONI, A.F. Avaliação do efeito da fotobiomodulação em úlcera traumática em crianças: relato de caso clínico. Revista Científica UMC, v.5, n.1, p.1-12, 2020. RIDIANDRIES, A.; TAN, J.; BURSILL, C.A. The role of chemokines in wound healing. International journal of molecular sciences, v.19, n.10, p.3217, 2018. RODRIGUES, C. F.; SILVA, S.; HENRIQUES, M. Candida glabrata: a review of its features and resistance. European journal of clinical microbiology & infectious diseases, v. 33, n. 5, p. 673-688, 2014. ROMERO, R.B.; ROMERO, A.L. Inibição de ciclooxigenases 1 (COX-1) e 2 (COX-2) por monoterpenos: um estudo in Silico. Journal of Health Sciences. v. 16, n.4, 2015. RUBIOLO, P. et al. “Essential oils and volatiles: sample preparation and analysis.” Flavour and Fragrance Journal, v. 25, p. 282- 290, 2010. RUFINO, A.T., et al. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of Ecaryophyllene, myrcene and limonene in a cell model of osteoarthritis. European Journal of Pharmacology, n.750, p.141-150, 2015. RUPP, H.; BINDER, W.H. 3D printing of core–shell capsule composites for post-reactive and damage sensing applications. Adv. Mater. Technol. v. 5, n. 2000509, 2020. RUSSO, E.B. Taming THC: potencial cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, v.163, n.7, p.1344-1364, 2011. SÁ, R.C.S.; ANDRADE, L.N.; SOUSA, D.P. A review on anti-inflammatory activity of monoterpenes. Molecules, v.19, p.1227-1254, 2013. SANTANA, C.P. et al. Compatibility study of dry extract of Ximenia americana L. and pharmaceutical excipients used in solid state. J Therm Anal Calorim, v. 133, p. 603–617, 2018. SANTOS, S B.D. et al. Oropharyngeal candidiasis in head and neck cancer patients in Iran: Species identification, antifungal susceptibility and pathogenic characterization. Anais Brasileiros de Dermatologia, v. 93, n. 3, p. 356–361, jun. 2018. SARACINO, I.M. et al. Antifungal activity of natural compounds vs. Candida spp.: A mixture of cinnamaldehyde and eugenol shows promising in vitro results. Antibiotics. v. 11, n. 73, 2022. SCHEMEL-SUÁREZ, M.; LÓPEZ-LÓPEZ, J.; CHIMENOS-KÜSTNER, E. Úlceras orales: diagnóstico diferencial y tratamiento. Medicina Clínica, [S. l.], v. 145, n. 11, p. 499–503, 2015. SCOTTI, L. et al. Experimental methodologies and evaluations of computer-aided drug design methodologies applied to a series of 2-aminothiophene derivatives with antifungal activities. Molecules (Basel, Switzerland), v. 17, n. 3, p. 2298–2315, 2012. SHARIFI-RAD, J. et al. Biological activities of essential oils: from plant chemoecology to traditional healing systems. Molecules, v.22, n.70, p. 1-55, 2017. SHIVAPPA, N. et al. Design, development and evaluation of microemulgel containing econazole nitrate. Int J Curr Res. v.10, n.8, p.72727-72733, 2018. SILVA, C.M. Formulação de gel termossensível mucoadesivo contendo cloridrato de pilocarpina para tratamento de xerostomia. 2017. 87f. Dissertação. (Mestrado em Ciências Farmacêuticas) – Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, 2017. SILVA D.C. et al. Treatment of Riga-Fede disease using laser therapy: clinical case report. RGO, v.65, n.1, p.87–91, 2017. SILVA, G.A. et al. Cancer mortality in the capitals and in the interior of Brazil: a four-decade analysis. Revista de Saúde Pública, v. 54, n. 126, p. 1-18, 2020. SILVA, I.C. Neutrófilos: Aspectos Clássicos, Plasticidade e Novas Funções Imunorregulatórias. Revista Interdisciplinar de Estudos Experimentais, v. 7, n. único, p. 35-46, 2015. SIMAS, D. L. R. et al. Caracterização dos óleos essenciais de frutas cítricas. Citrus Research & Technology, Cordeirópolis, v. 36, n. 1, p. 15-26, 2015. SLAUGHTER, B.V. et al. Hydrogels in Regenerative Medicine. Adv. Mater., v. 21, p. 3307-3329, 2009. SOARES, et al. Tratamento das ulcerações traumáticas bucais causadas por aparelhos ortodônticos. Revista Dental Press de Ortodontia e Ortopedia Facial, [S. l.], v.10, n.5, p.30–36, 2005. SONIS, S.T. et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer, v. 100, s. 9, p. 1995-2025, 2004. SOUSA, D.P. Medicinal Essential Oils: Chemical, Pharmacological and therapeutic aspects, 1st ed.; Nova Science Publishers: New York, NY, USA, p. 236, 2012. SOUSA, J.P.S. et al. Óleos vegetais como promotores de permeação cutânea em formulações tópicas e transdérmicas de anti-inflamatórios: uma revisão integrativa. Research, Society and Development, v. 10, n. 12, e541101220308, 2021. SPEZZIA, S. Mucosite oral em pacientes cancerosos submetidos a tratamento quimioterápico. Revista Ciências e Odontologia, v. 4, n. 1, p. 36–40, 2020. SUMITRA, M. et al. Emblica officinalis exerts wound healing action through up-regulation of collagen and extracellular signal-regulated kinases (ERK1/2). Wound Rep. Regen, v.17, p. 99–107, 2009. SUMIWI, S.A. et al. A study to predict anti-inflammatory activity of eugenol, myristicin, and limonene of Cinnamomum sintoc. International Journal of Pharmacy and Pharmaceutical Sciences, v. 7, n. 12, p. 51–54, 2015. SUN, J. D-limonene: safety and clinical applications. Alternative Medicine Review, v. 12, n. 3, p. 259-264, 2007. TAKEDA, K.; AKIRA, S. TLR signaling pathways. Paper presented at the Seminars in immunology, 2004. TANIDEH, N.; BADIE, A.; HABIBAGAHI, R. Effect of topical 2 % eucalyptus extract on 5-FU -induced oral mucositis in male golden hamsters. Brazilian Dental Journal, v. 31, p. 310–318, 2020. TASNEEM, S.; LIU, B.; LI, B.; CHOUDHARY, M.I.; WANG, W. Molecular pharmacology of inflammation: medicinal plants as anti-inflammatoryagents. Pharmacological Research, 2018. TATAVARTI, A.S.; HOAG, S.W. Microenvironmental pH modulation based release enhancement of a weakly basic drug from hydrophilic matrices, Journal of Pharmaceutical Sciences, v. 95, n. 7, 2006. THAKRAR, P.; CHAUDHRY, S.I. Oral Ulceration: An overview of diagnosis and management. Primary dental journal, [S. l.], v.5, n.1, p.30–33, 2016. THAKRE, A. et al. Limonene inhibits Candida albicans growth by inducing apoptosis. Medical Mycology, v. 56, p. 565–578, 2018. THEIS, N.; LERDAU, M. “The evolution of function in plant secondary metabolites.” International Journal of Plant Sciences, v. 164, n. 3, p. 93–102, 2003. TOMASSETTI, M. et al. Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms and in some binary mixtures. J Pharm Biomed Anal, v. 37, n.5, p. 949-55, 2005. TRANCHIDA, P.Q. et al. “Analysis of Citrus essential oils: state of the art and future perspectives. A review.” Flavour and Fragrance Journal, v. 27, p. 98-123, 2012. VALE, F.A. et al. Low-level laser therapy in the treatment of recurrent aphthous ulcers: a systematic review. Scientific World J. v.2015:150412, 2015. VALENTINO, A. et al. Thermo-responsive gel containing hydroxytyrosol-chitosan nanoparticles ( hyt@tgel ) counteracts the increase of osteoarthritis biomarkers in human chondrocytes. Antioxidants, v. 11, p. 1–17, 2022. VALÉRIO, D.A.R. et al. Anti-inflammatory and analgesic effects of the sesquiterpene lactone budlein A in mice: Inhibition of cytokine production-dependent mechanism. Eur. J. Pharmacol, v.562, p.155–163, 2007. VALLE, L.A. et al. Laser de baixa intensidade no tratamento de úlceras traumáticas: relato de casos. RevAssocPaulCir Dent, v.71, n.1, p.30-34, 2017. VERMONDEN, T.; CENSI, R.; HENNINK, W.E. Hydrogels for Protein Delivery. Chemical Reviews, v. 112, p. 2853-2888, 2012. VIEIRA, A. J. et al. Limonene: Aroma de inovação em saúde e doença. Interações Químico-Biológicas, v. 283, p. 97–106, 2018. VILELA-GOULART, M. DAS G. et al. Homogenous amniotic membrane as a biological dressing for oral mucositis in rats: Histomorphometric analysis. Archives of Oral Biology, v. 53, n. 12, p. 1163–1171, 2008. VILLA, A.; SONIS, S. T. An update on pharmacotherapies in active development for the management of cancer regimen-associated oral mucositis. Expert opinion on pharmacotherapy, Inglaterra, p. 1-8, 2020. WADE, W.G. The oral microbiome in health and disease. Pharmacol Res, v.69, n.1, p.137-43, 2013. WANG, P. H. et al. Wound healing. Journal of the Chinese Medical Association, v.81, n.2, p.94-101, 2018. WANG, Y. et al. In silico ADME/T modelling for rational drug design. Quarterly reviews of biophysics. v. 48, n.4, p. 488-515, 2015. WRÓBLEWSKA, M.; SZYMANSKA, E.; WINNICKA, K. The Influence of tea tree oil on antifungal activity and pharmaceutical characteristics of pluronic® f-127 gel formulations with ketoconazole. Int. J. Mol. Sci. v.22, n.11326, 2021. WU, L.C. et al. Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS induced inflammatory mediators. Journal of Agricultural and Food Chemistry. v. 56, n.7, p. 2341-2349, 2008. WU, Y. et al. Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer letters, v. 345, n. 2, p. 164-173, 2014. WYNN, R.L. Aloe vera gel: update for dentistry. General Dentistry, v. 53, p.6-9, 2005. XIMENES, R.M. et al. Anti-nociceptive and wound healing activities of Croton adamantinus Müll. Arg. essential oil. J. Nat. Med, v. 67, p.758–764, 2013. YADAV, S.K. et al. Emulgel: Uma nova abordagem para melhor administração tópica de medicamentos. Int. J. Curr. Farm. Res.v.9, p.15–19, 2016. YANG, L.; PANG, Y.; MOSES, H. L. TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends in immunology, v. 31, n. 6, p. 220-227, 2010. YILMAZ, B. S.; ÖZBEK, H. Investigation of the anti-inflammatory, hypoglycemic activity and median lethal dose (LD50) level of limonene in mice and rats. Acta Pharmaceutica Sciencia, v. 56, n. 1, p. 85–94, 2018. YOUSUF, M. et al. Chemical profiling, formulation development, in vitro evaluation and molecular docking of Piper nigrum Seeds Extract Loaded Emulgel for Anti-Aging. Molecules, v. 27, n. 5990, 2022. ZAHI, M. R.; LIANG, H.; YUAN, Q. Improving the antimicrobial activity of D- Limonene using a novel organogel-based nanoemulsion. Food Control., v. 50, p. 554-559, 2015. ZAPATA-ZAPATA, C. et al. In vitro activity of essential oils distilled from colombian plants against Candida auris and other Candida species with different antifungal susceptibility profiles. Molecules, v. 27, n. 6837, 2022. ZHANG, X. Z. et al. Synergistic inhibitory effect of berberine and d-limonene on human gastric carcinoma cell line MGC803. Journal of Medicinal Food, v. 17, n. 9, p. 955–962, 2014. ZHOU, P.R.; HUA, H.; LIU, X.S. Quantity of Candida colonies in saliva: a diagnost evalution for oral Candidiasis. The Chinese Journal of Dental Research, v. 20, n. 1, p. 27-32, 2017. ZULAK, K.G.; BOHLMANN, J. “Terpenoid biosynthesis and specialized vascular cells of conifer defense.” Journal of Integrative Plant Biology, v. 52, p. 86–97, 2010.188746850794111162600600600524871450381110278-2070498469879244349FitoterapiaÚlceras traumáticasMucosa oralCIENCIAS DA SAUDE::ODONTOLOGIADesenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oralDevelopment of emulgel based on R-(+)-limonene for the treatment of traumatic oral cavity ulcersinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/embargoedAccessreponame:Biblioteca Digital de Teses e Dissertações da UEPBinstname:Universidade Estadual da Paraíba (UEPB)instacron:UEPBORIGINALTS - Adyelle Dantas Ribeiro.pdfTS - Adyelle Dantas Ribeiro.pdfapplication/pdf2804948http://tede.bc.uepb.edu.br/jspui/bitstream/tede/4722/2/TS+-+Adyelle+Dantas+Ribeiro.pdf1e5fce1976e9cb93fc59be3fbc25b169MD52Termo de Depósito BDTD.pdfTermo de Depósito BDTD.pdfapplication/pdf161528http://tede.bc.uepb.edu.br/jspui/bitstream/tede/4722/3/Termo+de+Dep%C3%B3sito+BDTD.pdffab0625b459776ae5c6d20d11d0915acMD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81960http://tede.bc.uepb.edu.br/jspui/bitstream/tede/4722/1/license.txt6052ae61e77222b2086e666b7ae213ceMD51tede/47222023-08-22 08:05:51.379oai:tede.bc.uepb.edu.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede.bc.uepb.edu.br/jspui/PUBhttp://tede.bc.uepb.edu.br/oai/requestbc@uepb.edu.br||opendoar:2023-08-22T11:05:51Biblioteca Digital de Teses e Dissertações da UEPB - Universidade Estadual da Paraíba (UEPB)false
dc.title.por.fl_str_mv Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
dc.title.alternative.eng.fl_str_mv Development of emulgel based on R-(+)-limonene for the treatment of traumatic oral cavity ulcers
title Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
spellingShingle Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
Ribeiro, Adyelle Dantas
Fitoterapia
Úlceras traumáticas
Mucosa oral
CIENCIAS DA SAUDE::ODONTOLOGIA
title_short Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
title_full Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
title_fullStr Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
title_full_unstemmed Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
title_sort Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral
author Ribeiro, Adyelle Dantas
author_facet Ribeiro, Adyelle Dantas
author_role author
dc.contributor.advisor1.fl_str_mv Pereira, Jozinete Vieira
dc.contributor.advisor1ID.fl_str_mv https://orcid.org/0000-0001-7225-6409
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8041850574045487
dc.contributor.advisor-co1.fl_str_mv Damasceno, Bolívar Ponciano Goulart de Lima
dc.contributor.advisor-co1ID.fl_str_mv https://orcid.org/0000-0002-0747-0297
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/6407334157973308
dc.contributor.referee1.fl_str_mv Pereira, Jozinete Vieira
dc.contributor.referee1ID.fl_str_mv https://orcid.org/0000-0001-7225-6409
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/8041850574045487
dc.contributor.referee2.fl_str_mv Silva, Diego Romário
dc.contributor.referee2ID.fl_str_mv https://orcid.org/0000-0001-9724-0147
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/0522585351371155
dc.contributor.referee3.fl_str_mv Oliveira Filho, Abrahão Alves de
dc.contributor.referee3ID.fl_str_mv https://orcid.org/0000-0002-7466-9933
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/7440461731944347
dc.contributor.referee4.fl_str_mv Damasceno, Bolívar Ponciano Goulart de Lima
dc.contributor.referee4ID.fl_str_mv https://orcid.org/0000-0002-0747-0297
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6407334157973308
dc.contributor.referee5.fl_str_mv Silva, Andrea Cristina Barbosa
dc.contributor.referee5ID.fl_str_mv https://orcid.org/0000-0001-8964-8919
dc.contributor.referee5Lattes.fl_str_mv http://lattes.cnpq.br/5097978858569561
dc.contributor.authorID.fl_str_mv https://orcid.org/0000-0001-8147-2592
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3858737000492701
dc.contributor.author.fl_str_mv Ribeiro, Adyelle Dantas
contributor_str_mv Pereira, Jozinete Vieira
Damasceno, Bolívar Ponciano Goulart de Lima
Pereira, Jozinete Vieira
Silva, Diego Romário
Oliveira Filho, Abrahão Alves de
Damasceno, Bolívar Ponciano Goulart de Lima
Silva, Andrea Cristina Barbosa
dc.subject.por.fl_str_mv Fitoterapia
Úlceras traumáticas
Mucosa oral
topic Fitoterapia
Úlceras traumáticas
Mucosa oral
CIENCIAS DA SAUDE::ODONTOLOGIA
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::ODONTOLOGIA
description Traumatic ulcers (UTs) of the oral mucosa consist of a group of common changes in the oral cavity that cause painful symptoms and affect the well-being of the patient. The therapies available for the treatment of these injuries are isolated in terms of application and the occurrence of adverse effects. In this context, the search for new therapeutic alternatives from medicinal plants, such as limonene, a terpene with properties of pharmacological interest, stands out. This study evaluated in silico and in vitro, the antifungal activity of R-(+)-limonene isolated on Candida spp, and incorporated into an emulgel its physicochemical properties, antifungal, toxicological, anti-inflammatory and healing action of this emulgel. Through the in silico assay, the probability of the biological potential of the monoterpene, its theoretical oral bioavailability and acute oral toxicity were evaluated. The following strains were used: C. albicans ATCC 10231, C. glabrata ATCC 90031, C. krusei ATCC 6258, C. tropicalis ATCC 750, C. parapsilosis (ATCC 22019) and clinical isolates of C. albicans A1, and C. albicans A2. The Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC) was determined by microdilution, its effect on the growth kinetics of C. albicans and its antifungal potential by logarithmic reduction. The physical-chemical properties of the emulgel based on R-(+)-limonene (ELI) were determined by means of pH, resistance to centrifugation, accelerated centrifugation and spreadability. Acute oral toxicity and clastogenic and aneugenic potential were evaluated in Mus musculus mice (2000mg/kg). Wistar rats were submitted to the application of 5% acetic acid in the buccal mucosa to evaluate the anti-inflammatory and healing potential of the formulation, through clinical and histopathological analysis. Data were analyzed using descriptive and inferential statistics, analyzed using GraphPad Prism 5.0® software, San Diego, CA, USA. The in silico assays estimated that R-(+)-limonene has a broad spectrum of action on microorganisms of great clinical importance. The MIC of R-(+)-limonene ranged from 656.25 µg/mL to 2625 µg/mL and was classified as fungistatic on the C. albicans strain (ATCC 10231), while for the other species its action was fungicide. R-(+)-limonene had a potentially significant effect on the growth kinetics of C. albicans (p<0.05). The ELI showed an acidic pH of 5.71 ± 0.11; 5.71 ± 0.09 and 5.97 ± 0.05 for formulation of the emulgel with R-(+)-limonene (ELI) at 1.2%, 2.4% and 5%, respectively, and 5.74 ± 0.21 for the control formulation, good stability and spreadability, as well as good viscosity. Through analysis of growth kinetics and logarithmic reduction, it can be seen that the product significantly inhibited the growth of C. albicans in all the different concentrations tested when compared to the growth control. ELI did not induce signs of acute toxicity in mice submitted to gavage treatment at a single dose of 2000 mg/kg and produced a statistically significant lower number of micronuclei compared to the positive control (cyclophosphamide 50 mg/kg) in mouse erythrocytes. R-(+)-limonene has been shown to be a potential antifungal agent against Candida species, both as an isolated compound and incorporated into the emulgel. The ELI showed low toxicity and mutagenicity, in addition to good anti-inflammatory and healing action in the treatment of UTs in the oral cavity of Wistar rats. Therefore, the developed formulation was considered promising for the treatment of UTs in the oral cavity.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-08-22T11:05:11Z
dc.date.issued.fl_str_mv 2023-07-31
dc.date.available.fl_str_mv 2999-12-31
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv RIBEIRO, Adyelle Dantas. Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral. 2023. 111 f. Tese (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande, 2023.
dc.identifier.uri.fl_str_mv http://tede.bc.uepb.edu.br/jspui/handle/tede/4722
identifier_str_mv RIBEIRO, Adyelle Dantas. Desenvolvimento de emulgel à base de R-(+)-limoneno para tratamento de úlceras traumáticas da cavidade oral. 2023. 111 f. Tese (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande, 2023.
url http://tede.bc.uepb.edu.br/jspui/handle/tede/4722
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 188746850794111162
dc.relation.confidence.fl_str_mv 600
600
600
dc.relation.department.fl_str_mv 524871450381110278
dc.relation.cnpq.fl_str_mv -2070498469879244349
dc.relation.references.por.fl_str_mv ABID, W. K.; ALYAA I. N. The efficacy of a new paste formulation as an alternative therapeutic agent for traum atic ulcers. Journal of Taibah University Medical Sciences, v.16, n.5, p.724–32, 2021. ADELI, E. The use of supercritical anti-solvent (SAS) technique for preparation of Irbesartan-Pluronic® F-127 nanoparticles to improve the drug dissolution. Powder Technology, v. 298, p. 65–72, 2016. AKGULLU, C. et al. Nebivolol to attenuate the effects of hyper- homocysteinaemia in rats. Atherosclerosis, v. 240, n. 1, p. 33e39-39, 2015. ALCOBA-FLÓREZ, J. et al. PCR protocol for specific identification of Candida nivariensis, a recently described pathogenic yeast. Journal of Clinical Microbiology, v. 43, n. 12, p. 6194–61946, dez. 2005. AMARAL, R.B. et al. A. Terapia de fotobiomodulação no tratamento das lesões orais da síndrome de Stevens-Johnson: relato de caso. Hurev, v.45, n.4, p.478–82, 2020. AMINI, R.; ASLE-ROUSTA, M.; AGHAZADEH, S. Hepatoprotective effect of limonene against chronic immobilization induced liver damage in rats. Naunyn-Schmiedeberg's Archives of Pharmacology, v. 393, p. 2053–2059, 2020. ANAND, V.; GULATI, M.; GOVILA, V.; ANAND, B. Low level laser therapy in the treatment of aphthous ulcer. Indian Journal of Dental Research, v.24, n.2, p.267-70, 2013. ANDISHEH-TADBIR, A. et al. The effect of indocyanine green-mediated photodynamic therapy in healing of experimentally induced oral mucosal traumatic ulcer in rat. Lasers in Medical Science, v.36, n.3, p.611-618, 2021. ANDRADE-JORGE, E. et al. Novel synthesis of isoindoline/isoindoline-1, 3-dione derivatives under solventless conditions and evaluation with the human D 2 receptor. Medicinal Chemistry Research. v. 26, n. 10, p. 2420-2431, 2017. ANVISA. Guia para a condução de estudos não clínicos de toxicologia e segurança farmacológica necessários ao desenvolvimento de medicamentos. Versão 2, p. 1–48, 2019. ANVISA. Guia de estudos de estabilidade. Versão 1, p. 1-47, 2019. APTE, R. N. et al. Effects of micro-environment-and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour–host interactions. European journal of cancer, v. 42, n. 6, p. 751-759, 2006. ARAÚJO, G.M.F. et al. Nanoemulsions Loaded with Amphotericin B: Development, Characterization and Leishmanicidal Activity. Curr Pharm Des, v. 25, n. 14, p. 1616-1622, 2019. ARAÚJO-FILHO, H.G. et al. D-limonene exhibits superior antihyperalgesic effects in a β-Cyclodextrincomplexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice. Neuroscience, v.358, p.158-169, 2017. AYUNINGTYAS, N.F. et al. Expression of VEGF and CD-31 in traumatic ulcer of diabetic Wistar rats after application of Citrus limon peel essential oil. Journal of Oral Biology and Craniofacial Research, v. 13, p. 380–385, 2023. BADEE, A.Z.M.; HELMY, S.A.; MORSY, N.F.S. Utilisation of orange peel in the production of a-terpineol by Penicillium digitatum (NRRL 1202). Food Chemistry, v.126, p.849–854, 2011. BALKWILL, F.; MANTOVANI, A. Cancer and inflammation: implications for pharmacology and therapeutics. Clinical Pharmacology & Therapeutics, v. 87, n. 4, p. 401-406, 2010. BARROSA, D.B. et al. Antifungal activity of terpenes isolated from the Brazilian Caatinga: a review. Brazilian Journal of Biology, v. 83, e. 270966, p. 1-9, 2023. BERCZI, I.; SZENTIVANYI, A. Cytokines and chemokines. In I. Berczi & A. Szentivanyi (Eds.), NeuroImmune Biology, v. 3, p. 191-220: Elsevier, 2003. BERKOW, E. L.; LOCKHART, S. R. Fluconazole resistance in Candida species: a current perspective. Infection and drug resistance, v. 10, p. 237, 2017. BHATTARAI, N.; GUNN, J.; ZHANG, M. Chitosan-based hydrogels for controlled, localized drug delivery. Advanced Drug Delivery Reviews, v. 62, n. 1, p. 83-99, 2010. BIESKI, I.G.C. et al. Potencial econômico e terapêutico dos óleos essenciais mais utilizados no Brasil. Revista Fitos, v. 15, n. 1, p. 125-137, 2022. Biolab Farmacêutica Ltda: São Paulo – Ad-Muc [citado 2022 mar 01]. Disponível em: https://consultaremedios.com.br/ad-muc/bula. BIZZO, H.R.; REZENDE, C.M. O Mercado de óleos essenciais no brasil e no mundo na última década. Quim. Nova, v. 45, n. 8, p. 949-958, 2022. BOGDAN, C.; RÖLLINGHOFF, M.; DIEFENBACH, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Current Opinion in Immunology, v. 12, n. 1, p. 64-76, 2000. BOONLAI, W. et al. The effect of the preservative methylparaben on the thermoresponsive gelation behavior of aqueous solutions of poloxamer 407. Journal of Molecular Liquids, v. 240, p. 622–629, 2017. BRASIL. Resolução RDC n0 48, de 16 de março de 2004. Dispõe sobre o registro de medicamentos fitoterápicos. Diário Oficial da União, p. 7, 2004. CANTÓN, R. et al. IRT and CMT β-lactamases and inhibitor resistance. Clinical Microbiology and Infection, v. 14, n. SUPPL. 1, p. 53–62, 2008. CARVALHO, P.A.G.; PEREIRA-JÚNIOR, A.J.A.; NEGREIROS, W.A. Avaliação da dor causada pela mucosite oral em pacientes oncológicos. Rev Dor. v.10, n.1, p.47-50, 2009. CASTEL, B.M.M. et al. As bases farmacológicas dos cuidados farmacêuticos: o caso dos AINEs. Acta Farmacêutica Portuguesa, v. 2, n. 2, p. 79-87, 2013. CAVALCANTE, G. M. et al. Experimental model of traumatic ulcer in the cheek mucosa of rats. Acta Cirúrgica Brasileira, v.26, p.227-234, 2011. CAVALCANTI, J.M. et al. The essential oil of Croton zehntneri and trans-anethole improves cutaneous wound healing. J. Ethnopharmacol, v.144, p.240–247, 2012. CENSI, R. et al. Hydrogels for protein delivery in tissue engineering. Journal of Controlled Release, v. 161, n. 2, p. 680–692, 2012. CHARYULU, N.P. et al. Emulgel: A boon for enhanced topical drug delivery. J Young Pharm, v. 13, n.1, p.76-79, 2021. CHENG, T. L. et al. Plasminogen/thrombomodulin signaling enhances VEGF expression to promote cutaneous wound healing. Journal of Molecular Medicine, v.96, n.12, p.1333-1344, 2018. CHI, G. et al. Suppression of MAPK and NF-κB pathways by limonene contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury. Inflammation, v. 36, n. 2, p. 501–511, 2013. CHIU, Y-H. et al. “Radiation-Induced swallowing dysfunction in patients with head and neck cancer: a literature review.” Journal of the Formosan Medical Association, 2021. CHO, K.S. et al. “Terpenes from forests and human health.” Toxicological Research, v. 33, p. 97-106, 2017. CIRIMINNA, R. et al. Limonene: A versatile chemical of the bioeconomy. Chemical Communications, v. 50, n. 97, p. 15288–15296, 2014. CLEELAND, R.; SQUIRES, E. Evalution of new antimicrobials in vitro and in experimental animal infections. In: Lorian, V. M. D. Antibiotics in Laboratory Medicine. New York: Willians; Wilkins, p. 739-788, 1991. CLEVELAND, A. A. et al. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: results from population-based surveillance. PloS one, v. 10, n. 3, p. e0120452, 2015. CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard NCCLS document M27- A3. Wayne, PA, 2008. Code of Federal Regulations (CFR), 40, 141, 261, 268.40, Office of the federal register, national archives and records administration. US Government Printing Office, Superintendent of Documents, Washington, DC. 2018. CORDELLA, C. et al. Use of differential scanning calorimetry (DSC) as a new technique for detection of adultertion in honeys. 1. Study of adulteration effect on honey thermal behavior. J Agric Food Chem; v. 203, p. 208-250, 2002. COSTA, M.R.C. et al. Aplicação da fotobiomodulação laser em úlceras traumáticas na cavidade oral: revisão integrativa da literatura. International Journal of Science Dentistry, v.2, n.61, p. 145-161, 2023. CUI, R.Z.; BRUCE, A.J.; ROGERS, R.S. Recurrent apthous stomatitis. Clin Dermatol, v.34, n.4, p.475-481, 2016. DAMY, S.B. et al. Aspectos fundamentais da experimentação animal - aplicações em cirurgia experimental. Revista da Associação Médica Brasileira, v. 56, n. 1, p. 103–111, 2010. DANTAS, M. G. B. et al. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Scientific World Journal, v. 2016, 2016. DA SILVA, M.R.; OLIVEIRA, R.G. Avaliação do efeito carcinogênico e anticarcinogênico do levonorgestrel através do teste de detecção de clones de tumores epiteliais em células de Drosophila melanogaster. Revista Perquirere. v. 14, n.1, p. 200-217, 2017. DASSOLER, M. et al. Perfil fitoquímico e ensaio farmacológico de Averrhoa carambola L. (Oxalidaceae). J. Bras. Fitom, v.2, p.4–8, 2004. D'ALESSIO, P.A., et al. Oral administration of d-limonene controls inflammation in rat colitis and displays antiinflammatory properties as diet supplementation in humans. Life Sciences, n.10, p. 24-26, 2013. D'ALESSIO, P.A., et al. Skin Repair Properties of d-Limonene and Perillyl Alcohol in Murine Models. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, v.13, p.29-35, 2014. D´ARRIGO, M. et al. In vitro evaluation of the activity of an essential oil from Pistacia vera L. variety Bronte hull against Candida sp. BMC Complementary and Alternative Medicine, v. 19, n. 6, p. 1-7, 2019. DE ALMEIDA, A.A.C. et al. Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide. Inflammation, v. 40, n. 2, p. 511–522, 2017. DE SOUZA, M. C. et al. Gastroprotective effect of limonene in rats: Influence on oxidative stress, inflammation and gene expression. Phytomedicine, v. 53, p. 37–42, 2019. DJEKIC, L.; ČALIJA, B.; MEDAREVIĆ, Đ. Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug. Journal of Molecular Liquids, v. 303, p. 112639, 2020. DEMYTTENAERE, J.; KIMPE, N.; Biotransformation of terpenes by fungi: Study of the pathways involved. Journal of Molecular Catalysis B: Enzymatic, v. 11, n. 4-6, p. 265-270, 2011. DEWAN, M. et al. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations. International Journal of Biological Macromolecules, v. 72, p. 706–710, 2015. DO AMARAL, J.F., et al. Antinociceptive effect of the monoterpene R-(+)-limonene in mice. Biological and Pharmaceutical Bulletin, n. 30, p. 1217-20, 2007. DOMARADZKA, D.; GUZIK, U.; WOJCIESZYŃSKA, D. Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs. Reviews in Environmental Science and Bio/Technology. v. 14, n. 2, p. 229-239, 2015. DOUGHARI, J.H.; BAZZA, M.J. Phytochemistry, GC-ms analysis, antioxidant and antibacterial potentials of limonene isolated from pericarp of Citrus sinensis. International Journal of Microbiology and Biotechnology, v. 5, n. 1, p. 22, 2020. EDWARDS, R.; HARDING, K.G. Bacteria and wound healing. Curr Opin Infect Dis, v.17, n.2, p.91-96, 2004. ELAD, S. et al. Topical immunomodulators for management of oral mucosal conditions, a systematic review; Part II: miscellaneous agents. Expert opinion on emerging drugs, [S. l.], v.16, n.1, p.183–202, 2011. EMING, S. A.; WYNN, T. A.; MARTIN, P. Inflammation and metabolism in tissue repair and regeneration. Science, v. 356, n. 6342, 1026–1030, 2017. ENOCH, S.; LEAPER, D.J. Basic science of wound healing. Surgery (Oxford), v.23, n.2, p.37-42, 2005. ERASTO, P.; VILJOEN, A.M. Limonene - A review: biosynthetic, ecological and pharmacological relevance. Natural Produts Communications, v.3, n.7, p.1193-1202, 2008. FALCÃO, H. et al. Review of the plants with anti-inflammatory activity studied in Brazil. Braz. J. Pharmacogn., v.15, p.381–391, 2005. FARAH, C.; LYNCH, N.; MCCULLOUGH, M. Oral fungal infections: an update for the general practitioner. Australian Dental Journal, v. 55, p. 48–54, jun. 2010. FELIPE, L.O.; BICAS, J.L. Terpenos, aromas e química dos compostos naturais. Química Nova na Escola, v. 39, n. 2, p. 120-130, 2017. FERNANDES, N.D.L., et al. Lesões erosivas e ulcerativas da mucosa oral: uma revisão da literatura. Research, Society and Development, v. 11, n. 9, e20411931702, 2022. FERRERO-MILIANI, L. et al. Inflamação crônica: Importância de NOD2 e NALP3 na geração de interleucina-1beta. Clin. Exp. imunol. v. 147, p.227–235, 2007. FINFTER, O. et al. Photobiomodulation (low-level laser) therapy for immediate pain relief of persistent oral ulcers in chronic graft-versus-host disease. SupportCareCancer, v.29, n.8, p.4529–4534, 2021. FITZGERALD, K. A. et al. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature, v. 413, n. 6851, p. 78, 2001. FITZPATRICK, S.G.; COHEN D.M.; CLARK, A.N. Ulcerated lesions of the oral mucosa: clinical and histologic review. Head and Neck Pathology, v.13, n.1, p.91-102, 2019. FRANCE K.; VILLA, A. Acute oral lesions. Dermatol Clin, v. 38,4p. 41-450, 2020. FUJISAWA, K.; MIYAMOTO, Y.; NAGAYAMA, M. Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa. Journal of Oral Pathology and Medicine, v. 32, n. 6, p. 358–366, 2003. GALLEGOS-FLORES, P.I. et al. Actividad antibacteriana de cinco compuestos terpenoides: carvacrol, limoneno, linalool, α-terpineno y timol. Tropical and Subtropical Agroecosystems, v. 22, p. 241–248, 2019. GASMI, B.A. et al. Oral aphthous: pathophysiology, clinical aspects and medical treatment. Archives of Razi Institute, v.76, n.5, p.1155-1163, 2021. GILMORE, T. D. Introduction to NF-κB: players, pathways, perspectives. Oncogene, v. 25, n. 51, p. 6680, 2006. GIULIANO, E. et al. Mucosal applications of poloxamer 407-based hydrogels: an overview. Pharmaceutics, v.10, n.3, p.159, 2018. GOMEZ, A.; NELSON, K.E. The oral microbiome of children: development, disease, and implications beyond oral health. Microb Ecol 2016. Sep 14. [Epub ahead of print]. GOMES, N. M. L. et al. Fitoterapia como opção de tratamento para a mucosite oral. Archives of Health Investigation, v. 10, n. 1, p. 11–17, 2021. GONZALEZ, A.C.D.O. et al. Wound healing - A literature review. Anais brasileiros de dermatologia, v.91, p.614-620, 2016. GONZÁLEZ ROMA, L. B. Ulceración por trauma crónico: una lesión simuladora. Informe de un caso clínico. Rev. Asoc. Odontol, v.108, n.2, p. 57-62, 2020. GUIMARÃES, I.N.O.; ANDRADE, L.G. Atuação farmacêutica frente ao uso indiscriminado de antiinflamatórios não esteroidais (aines) por hipertensos. Revista Ibero-Americana de Humanidades, Ciências e Educação. São Paulo, v.8, n. 4, 2022. GUIMARÃES, M.A.; MÁZARO, T. Princípios éticos e práticos do uso de animais de experimentação. São Paulo: Universidade Federal de São Paulo, 2004. GUNAL, M.Y.; HEPER, A.O.; ZALOGLU, N. The effects of topical carvacrol application on wound healing process in male rats. Pharmacogn. J, v.6, p.10–14, 2014. HANSEN, J.S.; et al. Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice. Journal of Immunotoxicology, v.13, n.6, p.793-803, 2016. HARPER, R.S., et al. Acid-induced demineralisation of human enamel as a function of time and pH observed using X-ray and polarised light imaging. Acta Biomater. v. 15, n.120, p.240-248, 2021. HAYASHI, M. et al. Ensaio de micronúcleo de eritrócitos de roedores in vivo. Mutation Research, v. 312, p. 293–304, 1994. HEINRICH, P. C. et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochemical Journal, v. 374(Pt 1), 2003. HIROTA, R. et al. Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinae-treated mice. Inhalation Toxicology, v. 24, n. 6, p. 373–381, 2012. HOOD, K. A. et al. Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule-stabilizing activity. Cancer Research, v. 62, n. 12, p. 3356–3360, 2002. HUANG, H. et al. Thermo-sensitive hydrogels for delivering biotherapeutic molecules: A review. Saudi Pharmaceutical Journal, v. 27, n. 7, p. 990–999, 2019. HUANG, X. L. et al. Anti-inflammatory and antinociceptive effects of active ingredients in the essential oils from Gynura procumbens, a traditional medicine and a new and popular food material. Journal of Ethnopharmacology, v. 239, n. January, p. 111916, 2019. JONGEDIJK, E. et al. Biotechnological production of limonene in microorganisms. Applied Microbiology and Biotechnology, v. 100, n. 7, p. 2927–2938, 2016. KAIMOTO, T.; et al. Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene. European Journal of Pain, v.20, n.7, p.1155-1165, 2016. KAPUGI, M.; CUNNINGHAM, K. Corticosteroids. Orthopedic nursing, [S. l.], v.38, n.5, p.336–339, 2019. KARODI, R. et al. Evaluation of the wound healing activity of a crude extract of Rubia cordifolia L. (Indianmadder) in mice. Int. J.Appl. Res. Nat. Prod, v.2, p.12–18, 2009. KARPINSKI, T.M. Essential oils of lamiaceae family plants as antifungals. Biomolecules, v. 10, n. 103, 2020. KENNEDY, A. D.; DELEO, F. R. Neutrophil apoptosis and the resolution of infection. Immunologic Research, v. 43, n. 1-3, p. 25-61, 2009. KESKIN, I. et al. Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on experimental wound healing, Biotechnic & Histochemistry, v.92, n.4, p.274-282, 2017. KIEL, M.; ENGESSER, K.H. The biodegradation vs. biotransformation of fluorosubstituted aromatics. Applied microbiology and biotechnology. v. 99, n. 18, p. 7433-64, 2015. KIM, Y.W. et al. Safety evaluation and risk assessment of d-Limonene. Journal of Toxicology and Environmental Health, v.16, n.1, p.17-38, 2013. KLEPSER, M.E. et al. Influence of test conditions on antifungal time-kill curve results: Proposal for standardized methods. Antimicrobial Agents and Chemotherapy, v. 42, n. 5, p. 1207–1212, 1998. KOBAYASHI, S. D.; DELEO, F. R. Towards a comprehensive understanding of the role of neutrophils in innate immunity: a systems biology-level approach. Wiley Interdiscip. Rev. Syst. Biol. Med., v. 1, n. 3, p. 309-333, 2009. KOH, T. J.; DIPIETRO, L. A. Inflammation and wound healing: the role of the macrophage. Expert reviews in molecular medicine, v.13, 2011. KONG, E. F. et al. Development and in vivo evaluation of a novel histatin-5 bioadhesive hydrogel formulation against oral candidiasis. Antimicrobial agents and chemotherapy, v. 60, n. 2, p. 881-889, 2015. KOZLOVSKY, A. et al. Effect of local antimicrobial agents on excisional palatal wound healing: a clinical and histomorphometric study in rats. J Clin Periodontol, v. 34, n.2, p.164-71, 2007. KUMMER, R. et al. Evaluation of anti-inflammatory activity of citrus latifolia Tanaka essential oil and limonene in experimental mouse models. Evidence- based Complementary and Alternative Medicine, v. 2013, 2013. KUROIWA, Y. et al. Nano-scale and molecular-level understanding of wet-milled indomethacin/poloxamer 407 nanosuspension with TEM, suspended-state NMR, and Raman measurements. International Journal of Pharmaceutics, v. 537, n. 1–2, p. 30– 39, 2018. LAMBI, J.N. et al. Synthesis, spectral properties and thermal behaviour of zinc(II) acetylsalicylate. Thermochim Acta, v. 398, n.1-2, p. 145-51, 2003. LAPPAS, C.M.; LAPPAS, N.T. D-Limonene modulates T lymphocyte activity and viability. Cellular Immunology, v. 279, n.1, p.30-41, 2012. LEÃO, D.A. Caracterização e avaliação da toxicidade da berberina encapsulada com poloxamer 407 em Drosophila Melanogaster. 2021. 86f. Dissertação. (Mestrado em Tecnologia em Alimentos) - Universidade Tecnológica do Paraná, Campo Mourão, 2021. LEITE-ANDRADE, M.C. et al. Antifungal effect and inhibition of the virulence mechanism of D-Limonene against Candida parapsilosis. Molecules, v. 27, n. 8884, 2022. LEITE, P. M.; CAMARGOS, L. M.; CASTILHO, R. O. Recent progess in phytotherapy: a brazilian perspective. European Journal of Integrative Medicine, v. 41, p. 101270, 2020. LEMES, R. S. et al. Chemical composition and antibacterial activity of essential oils from Citrus aurantifolia leaves and fruit peel against oral pathogenic Bactéria. Annals of the Brazilian Academy of Sciences, v. 90, n. 2, p. 1285- 1292, 2018. LI, P.H.; CHIANG, B.H. Process optimization and stability of D-limonene-in water nanoemulsions prepared by ultrasonic emulsification using response surface methodology. Ultrasonics Sonochemistry, v.19, p.192–197, 2012. LI, W. et al. “Prevalence of dental erosion among people with gastroesophageal reflux disease in China.” The Journal of Prosthetic Dentistry, v.117, n.1, p.48–54, 2017. LI, X. et al. In silico prediction of chemical acute oral toxicity using multi-classification methods. Journal of chemical information and modeling.v. 54, n. 4, p. 1061-1069, 2014. LIMA, A.A.S.D.; GRÉGIO, A.M.T.; TANAKA, O.; MACHADO, M.Â.N.; FRANÇA, B.H.S. Tratamento das ulcerações traumáticas bucais causadas por aparelhos ortodônticos. Revista Dental Press de Ortodontia e Ortopedia Facial, v.10, p.30-36, 2005. LIMA DF, et al. Antinociceptive activity of the monoterpene alpha-phellandrene in rodents: possible mechanisms of action. Journal of Pharmacy and Pharmacology, v. 64, n.2, p. 283–92, 2012. LIU, Y. et al. Inhibitory efects of citrus lemon oil and limonene on Streptococcus sobrinus - Induced Dental Caries in Rats. Archives of Oral Biology, v. 118, p. 1-6, 2020. LOKE, C. et al. Factors affecting intra-oral pH - a review. Journal of oral rehabilitation, v.43, n.10, p.778–785, 2016. MAMEDE, L.C. et al. Comportamento térmico de alguns fármacos e medicamentos. Rev. Ciênc. Farm. Básica Apl., v. 27, n.2, p.151-155, 2006. MANDELBAUM, S.H. et al./ done at the Dermatology Service of the Teaching Hospital of Taubate, Dermatology course, MANDELBAUM, DI SANTIS & MANDELBAUM 393 An bras Dermatol. [S. l.], v. 78, n. 4, p. 393–410, 2003. MANSANO-SCHLOSSER, T.C.; CEOLIM, M.F. Qualidade de vida de pacientes com câncer no período de quimioterapia. Enfermagem, v.21, n.3, p.600-607, 2012. MARIANO, R.C.et al. Effect of topical application of chlorhexidine and metronidazole on the tissue repair of palatal wounds of rats: a clinical and histomorphometric study. Oral Surg Oral Med Oral Pathol Oral Radiol, v.119, n.5, p.505-513, 2015. MARÓSTICA, M. R.; PASTORE, G. M. Biotransformação de limoneno: Uma revisão das principais rotas metabólicas. Quimica Nova, v. 30, n. 2, p. 382– 387, 2007. MATOS, J.R.; MERCURI, L.; BARROS, G. Análise térmica aplicada a fármacos e medicamentos. In: STORPIRTIS, S. et al. Biofarmacocinética. Rio de Janeiro: Guanabara Koogan, 2009. cap. 4. p. 32-65. MAZZO, J. S O. et al. Desenvolvimento farmacotécnico de formulações de fotoprotetores FPS 30 e avaliação da estabilidade preliminar. Brazilian Journal of Development. v. 6, n. 8, p. 63696-63711, 2020. MEERAN, M.F.N. et al. O limoneno pode ser um possível candidato para avaliação como agente ou adjuvante contra infecção, imunidade e inflamação no COVID-19? Heliyon, v. 6, e05703, 2020. MELLO, G.D.; DANTAS, J.P.S.; BORGES, L.L. Busca in silico de moléculas com potencial antitumoral a partir da espécie Aloysia citriodora. Revista Brasileira Militar de Ciências, v. 7, n. 17, 2021. MELO et al., Cicatricial effect of Libidibia ferrea L. orabase formulation on traumatic ulcers oral in rats. Concilium, v.23, n.3, p.357-371, 2023. MIA, M. M.; BANK, R. A. The pro-fibrotic properties of transforming growth factor on human fibroblasts are counteracted by caffeic acid by inhibiting myofibroblast formation and collagen synthesis. Cell and Tissue Research, v.363, n.3, p.775-789, 2016. MIGUEL, M.G. “Antioxidant and anti-inflammatory activities of essential oils: a short review.” Molecules, v. 15, p. 9252-9287, 2010. MILLAN, J.; RIDLEY, A.J.; Rho GTPases and leucocyte-induced endothelial remodeling. Biochem. J., v.385, p.329-337, 2005. MILLSOP, J.W.; FAZEL, N. Oral candidiasis. Clinics in Dermatology, v. 34, n. 4, p. 487–494, jul. 2016. MIRANDA-CADENA, K. et al. Prevalence and antifungal susceptibility profiles of Candida glabrata, Candida parapsilosis and their close-related species in oral candidiasis. Archives of Oral Biology, v. 95, p. 100–107, nov. 2018. MITROPOULOU, G. et al. Citrus medica essential oil exhibits significant antimicrobial and antiproliferative activity. LWT - Food Science and Technology, v. 84, p. 344–352, 2017. MORAES, T. M. et al. Healing actions of essential oils from Citrus Aurantium and d-limonene in the Gastric Mucosa: The roles of VEGF, PCNA, and COX-2 in cell proliferation. Journal of Medicinal Food, v. 16, n. 12, p. 1162–1167, 2013. MORAIS, L.A.S. Influência dos fatores abióticos na composição química dos óleos essenciais. Horticultura Brasileira, v. 27, p. 4050- 4063, 2009. MOSVIN, C.V.; BUYLIN, B.A. Foundations of Laser Therapy. Triada Moskow, v.256, 2006. MOURA, A.B.R. et al. Candidíase pseudomembranosa em crianças com idade pré-escolar: uma breve revisão de literatura. Brazilian Journal of Surgery and Clinical Research - BJSCR, v. 26, n. 2, p. 80–84, 2019. MUNOZ, J.E. et al. In Vitro and In Vivo inhibitory activity of limonene against diferent isolates of Candida spp. J. Fungi, v. 6, n. 183, 2020. MUTHUKUMAR, T. et al. Effect of growth factors and pro-inflammatory cytokines by the collagen biocomposite dressing material containing Macrotyloma uniflorum plant extract-in vivo wound healing. Colloids and Surfaces B: Biointerfaces, v.121, p.178-188, 2014. NASCIMENTO, M. H. M. et al. Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release. International Journal of Biological Macromolecules, v. 111, p. 1245–1254, 2018. NIE, S. et al. Thermoreversible pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: In vitro drug release, cell cytotoxicity, and uptake studies. International Journal of Nanomedicine, v. 6, n. 1, p. 151–166, 2011. NOMURA E.C. et al. Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice. Journal of Ethnopharmacology, v. 150, n.2, p.583-589, 2013. OCDE. Diretrizes da OCDE para teste de produtos químicos. n. 19, p. 1–22, 2001 OLIVEIRA, B.V. et al. TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats. J Appl Oral Sci, v. 24, n. 3, p. 278-290, 2016. OLIVEIRA, M. A. et al. Análise térmica aplicada a fármacos e formulações farmacêuticas na indústria farmacêutica. Quim. Nova, v. 34, n. 7, p.1224-1230, 2011. OLIVEIRA, M.L. et al. Topical continuous use of Lippia sidoides Cham essential oil induces cutaneous inflammatory response, but does not delay wound healing process. J. Ethnopharmacol, v.153, p.283–289, 2014. OLIVEIRA, M.M.C. et al. O Uso Crônico de anti-inflamatórios não-esteroidais e seus efeitos adversos. Revista Caderno de Medicina, v. 2, n. 2, 2019. OMRAN, S. M. et al. The effects of limonene and orange peel extracts on some spoilage fungi. International Journal of Molecular and Clinical Microbiology, v. 1, p. 82-86, 2011. PARAMASHIVAM, S.K. et al. In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases. Bioinformation.v. 11, n. 2, n. 73, 2015. PARK, H.M. et al. Limonene, a natural cyclic terpene, is an agonistic ligant for adenosine A (2A) receptors. Biochemical and Biophysical Research Communications, n. 404, p. 345-348, 2011. PAULO FILHO, W.; RIBEIRO, J.E.; PINTO, D.S. Safety and efficacy of Eupatorium laevigatum paste as therapy for buccal aphthae: randomized, double-blind comparison with triamcinolone 0.1% orabase. Advances in therapy, v.32, n.4, p.375-378, jul. 2000. PEREIRA, G. C. et al. Avaliação da estabilidade de um xampu produzido com adição de óleo essencial de alecrim (Rosmarinus officinalis). Revista Teccen. v. 13, n.1, p. 02-07, 2020. PETERSON, D.E.; BENSADOUN, R. J.; ROILA, F. Management of oral and gastrointestinal mucositis: ESMO clinical practice guidelines. Annals of Oncology, v. 22, n. SUPPL. 6, p. 78–84, 2011. PINTO, E. et al. Antifungal activity of Thapsia villosa essential oil against Candida, Cryptococcus, Malassezia, Aspergillus and Dermatophyte Species. Molecules, v. 22, p. 1-11, 2017. PINTO, E. et al. Antifungal activity of Ferulago capillaris essential oil against Candida, Cryptococcus, Aspergillus and dermatophyte species. Eur J Clin Microbiol Infect Dis, v. 32, p. 1311–1320, 2013. PIRES JUNIOR, H. B. Efeitos toxicológicos agudos de estrato de frutos verdes de Meliaazedarach (MELIACEAE) em ratos (Rattusnovergiucus), camundongos (Musmusculares) e Artemia salina. 2010. 70f. Dissertação. (Mestrado em Ciência Animal) - Escola de Veterinária, Universidade Federal de Goiás, Goiânia, 2010. PORTOU, M. J. et al. The innate immune system, toll-like receptors and dermal wound healing: a review. Vascular pharmacology, v.71, p.31-36, 2015. PULITO, C. et al. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res, v. 39, n. 1, p. 210, 2020. PUSPASARI, A. et al. Effects of topical application of propolis extract on fibroblast growth factor-2 and fibroblast expression in the traumatic ulcers of diabetic Rattus norvegicus. J Oral Maxillofac Pathol., v.22, n.1, p.54-58, 2018. REHMAN, M.U., et al. D-limonene suppresses doxorubicininduced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats. Experimental Biology and Medicine, n.239, p. 465-476, 2014. RENNICK, L.A. et al. Effectiveness of a novel topical powder on the treatment of traumatic oral ulcers in orthodontic patients: A randomized controlled trial. AngleOrthod, v.86, n.3, p.351–357, 2016. RIBEIRO, T.E.; MARANGONI, A.F. Avaliação do efeito da fotobiomodulação em úlcera traumática em crianças: relato de caso clínico. Revista Científica UMC, v.5, n.1, p.1-12, 2020. RIDIANDRIES, A.; TAN, J.; BURSILL, C.A. The role of chemokines in wound healing. International journal of molecular sciences,
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Estadual da Paraíba
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Odontologia - PPGO
dc.publisher.initials.fl_str_mv UEPB
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Pró-Reitoria de Pós-Graduação e Pesquisa - PRPGP
publisher.none.fl_str_mv Universidade Estadual da Paraíba
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UEPB
instname:Universidade Estadual da Paraíba (UEPB)
instacron:UEPB
instname_str Universidade Estadual da Paraíba (UEPB)
instacron_str UEPB
institution UEPB
reponame_str Biblioteca Digital de Teses e Dissertações da UEPB
collection Biblioteca Digital de Teses e Dissertações da UEPB
bitstream.url.fl_str_mv http://tede.bc.uepb.edu.br/jspui/bitstream/tede/4722/2/TS+-+Adyelle+Dantas+Ribeiro.pdf
http://tede.bc.uepb.edu.br/jspui/bitstream/tede/4722/3/Termo+de+Dep%C3%B3sito+BDTD.pdf
http://tede.bc.uepb.edu.br/jspui/bitstream/tede/4722/1/license.txt
bitstream.checksum.fl_str_mv 1e5fce1976e9cb93fc59be3fbc25b169
fab0625b459776ae5c6d20d11d0915ac
6052ae61e77222b2086e666b7ae213ce
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UEPB - Universidade Estadual da Paraíba (UEPB)
repository.mail.fl_str_mv bc@uepb.edu.br||
_version_ 1800227529129197568

Registros relacionados