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dc.contributor.authorCruz, Tamires de Almeida-
dc.date.accessioned2026-07-16T14:19:37Z-
dc.date.available2026-07-16T14:19:37Z-
dc.date.issued2025-12-12-
dc.identifier.citationCRUZ, Tamires de Almeida. Análise dos efeitos biológicos de extratos da espécie vegetal Cannabis sativa (Linnaeu) em modelos de estudos de agregação de proteínas associadas a doenças neurodegenerativas. 2025. 173 f. Tese (Doutorado em Química) - Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2025.pt_BR
dc.identifier.urihttp://rima.ufrrj.br/jspui/handle/20.500.14407/25807-
dc.description.abstractAs doenças neurodegenerativas, como Parkinson e Alzheimer, envolvem perda progressiva de neurônios e agregação de proteínas, incluindo α-sinucleína (aSyn) e β-amiloide (Aβ42). Estratégias capazes de reduzir o estresse oxidativo e modular a agregação proteica são de grande interesse terapêutico. A Cannabis sativa apresenta composição química diversificada, incluindo canabinoides, flavonoides e terpenos, cujas interações biológicas ainda não foram totalmente exploradas. Neste estudo, quatro extratos hidrometanólicos de C. sativa, provenientes de diferentes genótipos e ricos em fitocanabinoides majoritários (THC, CBD e CBN), foram avaliados quanto a toxicidade, atividade antioxidante, proteção mitocondrial e modulação de agregação proteica. Utilizou-se Saccharomyces cerevisiae (cepas BY4741 e Δyap1) não transformadas e transformadas com genes de aSyn ou Aβ42, além de células humanas H4 expressando aSyn. A caracterização fitoquímica revelou que os extratos apresentavam diferentes proporções de THC (69,88 %), CBD (52,64 %) e CBN (47,38–58,64 %). Os extratos não apresentaram toxicidade relevante e mantiveram viabilidade celular em todas as cepas, incluindo Δyap1, demonstrando ação independente do sistema antioxidante endógeno. Evidenciou- se forte efeito antioxidante, revertendo o desbalanço redox induzido por aSyn e Aβ42. A proteção mitocondrial foi seletiva, ocorrendo frente a Aβ42, mas não a aSyn. Em células H4, os extratos reduziram inclusões de aSyn e aumentaram a proporção de células livres de agregados. Em conclusão, os extratos de C. sativa exibem potencial antioxidante e modulador da agregação proteica, com efeitos seletivos sobre a função mitocondrial, fornecendo subsídios experimentais sólidos para futuras estratégias terapêuticas contra desordens neurodegenerativas.pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESpt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal Rural do Rio de Janeiropt_BR
dc.subjectCannabis sativapt_BR
dc.subjectdoenças neurodegenerativaspt_BR
dc.subjectα-sinucleínapt_BR
dc.subjectbeta-amiloidept_BR
dc.subjectSaccharomyces cerevisiaept_BR
dc.subjectcélulas H4pt_BR
dc.subjectneurodegenerative diseasespt_BR
dc.subjectalpha-synucleinpt_BR
dc.subjectamyloid-betapt_BR
dc.subjectH4 cellspt_BR
dc.titleAnálise dos efeitos biológicos de extratos da espécie vegetal Cannabis sativa (Linnaeu) em modelos de estudos de agregação de proteínas associadas a doenças neurodegenerativaspt_BR
dc.title.alternativeAnalysis of the biological effects of extracts from the plant species Cannabis sativa (Linnaeu) extracts in models of protein aggregation associated with neurodegenerative diseasesen
dc.typeTesept_BR
dc.description.abstractOtherNeurodegenerative diseases, such as Parkinson's and Alzheimer's, involve progressive loss of neurons and protein aggregation, including α-synuclein (aSyn) and β-amyloid (Aβ42). Strategies capable of reducing oxidative stress and modulating protein aggregation are of great therapeutic interest. Cannabis sativa has a diverse chemical composition, including cannabinoids, flavonoids, and terpenes, whose biological interactions have not yet been fully explored. In this study, four hydromethanolic extracts of C. sativa, derived from different genotypes and rich in major phytocannabinoids (THC, CBD, and CBN), were evaluated for toxicity, antioxidant activity, mitochondrial protection, and protein aggregation modulation. Untransformed and transformed Saccharomyces cerevisiae (strains BY4741 and Δyap1) with aSyn or Aβ42 genes were used, as well as human H4 cells expressing aSyn. Phytochemical characterization revealed that the extracts had different proportions of THC (69.88%), CBD (52.64%), and CBN (47.38–58.64%). The extracts showed no relevant toxicity and maintained cell viability in all strains, including Δyap1, demonstrating action independent of the endogenous antioxidant system. A strong antioxidant effect was evident, reversing the redox imbalance induced by aSyn and Aβ42. Mitochondrial protection was selective, occurring in the presence of Aβ42 but not aSyn. In H4 cells, the extracts reduced aSyn inclusions and increased the proportion of aggregate-free cells. In conclusion, C. sativa extracts exhibit antioxidant and protein aggregation modulating potential, with selective effects on mitochondrial function, providing solid experimental support for future therapeutic strategies against neurodegenerative disorders.en
dc.contributor.advisor1Riger, Cristiano Jorge-
dc.contributor.advisor1IDhttps://orcid.org/0000-0002-7579-5958pt_BR
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/8756160468801705pt_BR
dc.contributor.advisor-co1Outeiro, Tiago Fleming-
dc.contributor.advisor-co1IDhttps://orcid.org/0000-0003-1679-1727pt_BR
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/2609917864602259pt_BR
dc.contributor.advisor-co2Chaves, Douglas Siqueira de Almeida-
dc.contributor.advisor-co2IDhttps://orcid.org/0000-0002-0571-9538pt_BR
dc.contributor.advisor-co2Latteshttp://lattes.cnpq.br/1864237318361425pt_BR
dc.contributor.referee1Riger, Cristiano Jorge-
dc.contributor.referee1IDhttps://orcid.org/0000-0002-7579-5958pt_BR
dc.contributor.referee1Latteshttp://lattes.cnpq.br/8756160468801705pt_BR
dc.contributor.referee2Gomes, Daniela Cosentino-
dc.contributor.referee2IDhttps://orcid.org/0000-0001-5690-5413pt_BR
dc.contributor.referee2Latteshttp://lattes.cnpq.br/3067190550867881pt_BR
dc.contributor.referee3Lacerda, Renata Barbosa-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/7054878061455899pt_BR
dc.contributor.referee4Eleutherio, Elis Cristina Araujo-
dc.contributor.referee4IDhttps://orcid.org/0000-0001-5842-2714pt_BR
dc.contributor.referee4Latteshttp://lattes.cnpq.br/7716423349207719pt_BR
dc.contributor.referee5Vieira, Tuane Cristine Ramos Goncalves-
dc.contributor.referee5IDhttps://orcid.org/0000-0002-3574-5411pt_BR
dc.contributor.referee5Latteshttp://lattes.cnpq.br/8183054978119804pt_BR
dc.creator.IDhttps://orcid.org/0000-0002-8596-8058pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/2426291444492935pt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentInstituto de Químicapt_BR
dc.publisher.initialsUFRRJpt_BR
dc.publisher.programPrograma de Pós-Graduação em Químicapt_BR
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