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Please use this identifier to cite or link to this item:
https://tede.ufam.edu.br/handle/tede/9649
???metadata.dc.type???: | Tese |
Title: | Atividade antidiabética da 4-Metoxichalcona isolada e nanoencapsulada |
???metadata.dc.creator???: | Rosales Acho, Leonard Domingo |
???metadata.dc.contributor.advisor1???: | Lima, Emersom Silva |
???metadata.dc.contributor.referee1???: | Borges, Rosivaldo dos Santos |
???metadata.dc.contributor.referee2???: | Souza, Tatiane Pereira de |
???metadata.dc.contributor.referee3???: | Menezes, Irwin Rose Alencar de |
???metadata.dc.contributor.referee4???: | Carvalho, Rosany Piccolotto |
???metadata.dc.description.resumo???: | O diabetes mellitus, uma alteração metabólica resultante de defeitos na secreção ou produção de insulina, tornou-se um sério problema de saúde pública em todo o mundo. Dadas as implicações das alterações metabólicas causadas pela diabetes na sociedade, economia e qualidade de vida, a busca por novas alternativas terapêuticas para essa doença é de extrema importância. Nesse contexto, o presente estudo teve como objetivo avaliar a atividade antidiabética da 4-metoxichalcona isolada (MPP) e de sua formulação nanoencapsulada (NC), por meio de ensaios in sílico, in vitro e in vivo. Inicialmente, a MPP foi sintetizada utilizando a reação de condensação de Claisen-Schmidt e, posteriormente, caracterizada e quantificada por RMN e espectrometria de massas. A nanoencapsulação do MPP resultou em uma formulação estável e de liberação prolongada, com características favoráveis, incluindo uma distribuição monomodal com tamanho de 187±3,85 nm, potencial zeta de -19,9 ± 0,72 mV, índice de polidispersão de 0,21 ± 0,007 e condutividade de 0,041 ± 0,004 mS. Essa formulação demonstrou estabilidade em ampla faixa de temperaturas (10 ̊C a 80 ̊C) e pH (1 a 5). A MPP apresentou resultados promissores, demonstrando ausência de toxicidade tanto in vitro quanto in vivo. Além disso, exibiu efeito hipoglicemiante em camundongos saudáveis e diabéticos durante o teste de tolerância oral à glicose (TTOG), embora não tenha apresentado o mesmo efeito no teste de tolerância oral à sacarose (TTOS). A administração oral tanto da MPP isolada quanto de sua formulação nanoencapsulada demonstrou efeito hipoglicemiante em camundongos diabéticos após tratamento de 7 semanas. Os níveis de glicemia obtidos com a nanocápsula contendo MPP (NC10 = 166±58) na dose de 10 mg kg-1 pc, metformina (MET200 = 199±64) e MPP (MPP200 = 123±44) na dose de 200 mg kg-1 pc foram estatisticamente equivalentes ao grupo não diabético (GN = 121±15), indicando que a nanoencapsulação potencializou em 20 vezes o efeito antidiabético da MPP. Além disso, foi observado um efeito antiglicante in vitro, e esses resultados foram corroborados pela redução dos níveis de HbA1c (%) nos grupos MET200, MPP200 e NC10, alcançando níveis comparáveis ao grupo não diabético (GN). É relevante destacar que o controle da glicemia foi alcançado sem causar dano hepático, conforme comprovado pelas baixas concentrações de malonaldeído (μmol/g) e pela histologia hepática. Esses resultados são de extrema relevância, uma vez que a MPP é uma molécula de baixo custo e de fácil obtenção. O desenvolvimento de uma nanoformulação ativa contendo essa molécula mostra-se como uma excelente opção terapêutica para o tratamento do diabetes. Assim, esse estudo contribui significativamente para a busca de novas abordagens farmacológicas no combate a essa doença metabólica crônica. Entretanto, são necessárias futuras investigações e ensaios clínicos para validar completamente o potencial terapêutico e a segurança dessa nanoformulação, de forma a viabilizar sua aplicação clínica e seu potencial como um medicamento eficaz no tratamento do diabetes mellitus. |
Abstract: | Diabetes mellitus, a metabolic disorder resulting from defects in insulin secretion or production, has become a serious public health problem worldwide. Given the implications of metabolic alterations caused by diabetes on society, economy, and quality of life, the search for new therapeutic alternatives for this disease is of utmost importance. In this context, the present study aimed to evaluate the antidiabetic activity of isolated 4-methoxychalcone (MPP) and its nanoencapsulated formulation (NC), through in silico, in vitro, and in vivo assays. Initially, MPP was synthesized using the Claisen-Schmidt condensation reaction and subsequently characterized and quantified by NMR and mass spectrometry. The nanoencapsulation of MPP resulted in a stable and sustained release formulation with favorable characteristics, including a monomodal distribution with a size of 187±3.85 nm, zeta potential of -19.9 ± 0.72 mV, polydispersity index of 0.21 ± 0.007, and conductivity of 0.041 ± 0.004 mS. This formulation demonstrated stability over a wide range of temperatures (10 ˚C to 80 ˚C) and pH (1 to 5). MPP showed promising results, demonstrating no toxicity both in vitro and in vivo. Furthermore, it exhibited hypoglycemic effects in both healthy and diabetic mice during the oral glicose tolerance test (TTOG), although it did not have the same effect in the oral sucrose tolerance test (TTOS). Oral administration of both isolated MPP and its nanoencapsulated formulation demonstrated hypoglycemic effects in diabetic mice after 7 weeks of treatment. The glycemia levels obtained with the MPP-containing nanocapsule (NC10 = 166±58) at a dose of 10 mg/kg bw, metformin (MET200 = 199±64), and MPP (MPP200 = 123±44) at a dose of 200 mg/kg bw were statistically equivalent to the non-diabetic group (GN = 121±15), indicating that nanoencapsulation potentiated the antidiabetic effect of MPP by 20 times. Additionally, an antiglycation effect was observed in vitro, and these results were confirmed by the reduction of HbA1c levels (%) in the MET200, MPP200, and NC10 groups, reaching levels comparable to the non-diabetic group (GN). Importantly, glycemic control was achieved without causing hepatic damage, as evidenced by the low malondialdehyde concentrations (µmol/g) and liver histology. These results are of great significance, as MPP is a low-cost and readily available molecule. The development of an active nanoformulation containing this molecule proves to be an excellent therapeutic option for diabetes treatment. Thus, this study significantly contributes to the search for new pharmacological approaches in the fight against this chronic metabolic disease. However, further investigations and clinical trials are necessary to fully validate the therapeutic potential and safety of this nanoformulation, enabling its clinical application and potential as an effective medication for diabetes mellitus treatment. Diabetes mellitus, a metabolic disorder resulting from defects in insulin secretion or production, has become a serious public health problem worldwide. Given the implications of metabolic alterations caused by diabetes on society, economy, and quality of life, the search for new therapeutic alternatives for this disease is of utmost importance. In this context, the present study aimed to evaluate the antidiabetic activity of isolated 4-methoxychalcone (MPP) and its nanoencapsulated formulation (NC), through in silico, in vitro, and in vivo assays. Initially, MPP was synthesized using the Claisen-Schmidt condensation reaction and subsequently characterized and quantified by NMR and mass spectrometry. The nanoencapsulation of MPP resulted in a stable and sustained release formulation with favorable characteristics, including a monomodal distribution with a size of 187±3.85 nm, zeta potential of -19.9 ± 0.72 mV, polydispersity index of 0.21 ± 0.007, and conductivity of 0.041 ± 0.004 mS. This formulation demonstrated stability over a wide range of temperatures (10 ˚C to 80 ˚C) and pH (1 to 5). MPP showed promising results, demonstrating no toxicity both in vitro and in vivo. Furthermore, it exhibited hypoglycemic effects in both healthy and diabetic mice during the oral glicose tolerance test (TTOG), although it did not have the same effect in the oral sucrose tolerance test (TTOS). Oral administration of both isolated MPP and its nanoencapsulated formulation demonstrated hypoglycemic effects in diabetic mice after 7 weeks of treatment. The glycemia levels obtained with the MPP-containing nanocapsule (NC10 = 166±58) at a dose of 10 mg/kg bw, metformin (MET200 = 199±64), and MPP (MPP200 = 123±44) at a dose of 200 mg/kg bw were statistically equivalent to the non-diabetic group (GN = 121±15), indicating that nanoencapsulation potentiated the antidiabetic effect of MPP by 20 times. Additionally, an antiglycation effect was observed in vitro, and these results were confirmed by the reduction of HbA1c levels (%) in the MET200, MPP200, and NC10 groups, reaching levels comparable to the non-diabetic group (GN). Importantly, glycemic control was achieved without causing hepatic damage, as evidenced by the low malondialdehyde concentrations (µmol/g) and liver histology. These results are of great significance, as MPP is a low-cost and readily available molecule. The development of an active nanoformulation containing this molecule proves to be an excellent therapeutic option for diabetes treatment. Thus, this study significantly contributes to the search for new pharmacological approaches in the fight against this chronic metabolic disease. However, further investigations and clinical trials are necessary to fully validate the therapeutic potential and safety of this nanoformulation, enabling its clinical application and potential as an effective medication for diabetes mellitus treatment. |
Keywords: | Diabetes - Tratamento Saúde pública |
???metadata.dc.subject.cnpq???: | CIENCIAS DA SAUDE: FARMACIA |
???metadata.dc.subject.user???: | Diabetes Glicação Nanocápsula Insolubilidade Toxicidade |
Language: | por |
???metadata.dc.publisher.country???: | Brasil |
Publisher: | Universidade Federal do Amazonas |
???metadata.dc.publisher.initials???: | UFAM |
???metadata.dc.publisher.department???: | Faculdade de Ciências Farmacêuticas |
???metadata.dc.publisher.program???: | Programa de Pós-graduação em Inovação Farmacêutica |
Citation: | ROSALES ACHO, Leonard Domingo. Atividade antidiabética da 4-Metoxichalcona isolada e nanoencapsulada. 2023. 207 f. Tese (Doutorado em Inovação Farmacêutica) - Universidade Federal do Amazonas, Manaus (AM), 2023. |
???metadata.dc.rights???: | Acesso Aberto |
URI: | https://tede.ufam.edu.br/handle/tede/9649 |
Issue Date: | 28-Apr-2023 |
Appears in Collections: | Doutorado em Inovação Farmacêutica |
Files in This Item:
File | Description | Size | Format | |
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TESE_LeonardAcho_PPGIF.pdf | 3.47 MB | Adobe PDF | Download/Open Preview |
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