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Artigo Anti-inflammatory agents as modulators of the inflammation in adipose tissue: a systematic review(Plos One, 2022) Morais, Ana Heloneida de Araujo; Nascimento, Sara Sayonara da Cruz; Queiroz, Jaluza Luana Carvalho de; Medeiros, Amanda Fernandes de; Nunes, Ana Clara de França; Piuvezam, Grasiela; Maciel, Bruna Leal Lima; Passos, Thais Souza; https://orcid.org/0000-0002-6460-911XObesity is characterized by an adipose tissue mass expansion that presents a risk to health, associated with a chronic increase in circulating inflammatory mediators. Anti-inflammatory agents are an obesity alternative treatment. However, the lack of effective agents indicates the need to assess the mechanisms and identify effective therapeutic targets. The present work identified and described the mechanisms of action of anti-inflammatory agents in adi pose tissue in experimental studies. The review was registered in the International Prospec tive Registry of Systematic Reviews (PROSPERO—CRD42020182897). The articles’ selection was according to eligibility criteria (PICOS). The research was performed in PubMed, ScienceDirect, Scopus, Web of Science, VHL, and EMBASE. The methodological quality evaluation was assessed using SYRCLE. Initially, 1511 articles were selected, and at the end of the assessment, 41 were eligible. Among the anti-inflammatory agent classes, eight drugs, 28 natural, and five synthetic compounds were identified. Many of these anti inflammatory agents act in metabolic pathways that culminate in the inflammatory cytokines expression reduction, decreasing the macrophages infiltration in white and adipose tissue and promoting the polarization process of type M1 to M2 macrophages. Thus, the article cla rifies and systematizes these anti-inflammatory agents’ mechanisms in adipose tissue, pre senting targets relevant to future research on these pathways.Tese Aspectos funcionais de peptídeos vegetais com efeito anti-inflamatório na obesidade e avaliação estrutural do inibidor de tripsina kunitz de sementes de tamarindo(Universidade Federal do Rio Grande do Norte, 2021-10-25) Medeiros, Amanda Fernandes de; Morais, Ana Heloneida de Araújo; Maciel, Bruna Leal Lima; 96256192320; http://lattes.cnpq.br/5790541670952158; http://lattes.cnpq.br/1233944493334651; http://lattes.cnpq.br/9221417221401426; Oliveira, Hermógenes David de; http://lattes.cnpq.br/4151792037839111; Pedrosa, Matheus de Freitas Fernandes; http://lattes.cnpq.br/2929963416385218; Machado, Richele Janaina Araújo; http://lattes.cnpq.br/1352905640097175; Lima, Severina Carla Vieira Cunha; http://lattes.cnpq.br/8818927353248941A inflamação subclínica no sobrepeso e na obesidade altera diversas vias metabólicas, com reforço positivo para o acúmulo de mais tecido adiposo e alteração no metabolismo energético. Diversos estudos têm avaliado o efeito anti-inflamatório e imunomodulador de proteínas hidrolisadas e peptídeos vegetais, sendo necessário, contudo, explorar os mecanismos de ação desses efeitos. Dessa maneira, no primeiro capítulo desta tese, foi apresentada na revisão narrativa a compreensão dos mecanismos de ação de proteínas hidrolisadas e peptídeos vegetais sobre a inflamação acometida pelo excesso de tecido adiposo. Para isso, realizou-se uma busca nas bases de dados, selecionando estudos que envolviam vias e respostas metabólicas alvos de proteínas hidrolisadas ou peptídeos de origem vegetal. Viu-se que os mecanismos perpassam a inibição da via NF-B, redução do estresse oxidativo, estímulo à via da PI3K-AKT e de enzimas relacionadas com a detoxificação (superóxido dismutase e catalase), assim, culminando na redução de citocinas e adipocinas inflamatórias, bem como a polarização de macrófagos para o fenótipo M2. No segundo capítulo foram apresentados os estudos in vitro e de simulação computacional (in silico) com o inibidor de tripsina purificado de sementes de tamarindo (Tamarindus indica L.) (ITTp). Essa proteína tem sido estudada in vitro e em estudos préclínicos para o tratamento da obesidade, de suas complicações e de comorbidades associadas. O ITTp foi sequenciado de novo por MALDI-TOF/TOF, foi obtida a sua modelagem por homologia e avaliada a interação com a enzima tripsina (PDB ID 2PTN) por meio de simulação de dinâmica molecular (DM) em condições controladas de temperatura, pressão e presença de água. Foram identificados 75 resíduos de aminoácidos adicionais da sequência do ITTp. A modelagem por homologia foi realizada pelo CONCOORD e validada pelo MolProbity e as quatro melhores conformações da modelagem foram submetidas à DM. A conformação n° 287 do modelo nº 56 foi selecionada, considerando a análise RMSD e a energia de interação (-301,0128 kcal.mol1 ). Os resíduos Ile (54), Pro (57), Arg (59), Arg (63) e Glu (78) do ITTp apresentaram menor energia de interação e por isso maior interação com a enzima tripsina (PDB ID 2PTN). Dentre esses, os resíduos de Arg (59 e 63) estavam, principalmente, envolvidos em seu mecanismo de ligação de modo eletrostático. Esses resultados favorecem a continuidade de estudos com o ITTp para aplicações em estudos pré-clínicos e clínicos na área de saúde, visando contribuir no controle de graves problemas de saúde pública, como a obesidade. Por fim, considerando os potenciais alvos moleculares terapêuticos apontados nas vias metabólicas inflamatórias para peptídeos vegetais no tratamento da obesidade, revelados por meio da revisão narrativa, além do sequenciamento, modelagem e dinâmica molecular do ITTp com a tripsina, por meio dos estudos in silico, esta tese aprofunda os conhecimentos sobre o ITTp e gera suporte para estudos futuros.Artigo Biochemical characterisation of a kunitz-type inhibitor from tamarindus indica L. seeds and its efficacy in reducing plasma leptin in an experimental model of obesity(Journal of Enzyme Inhibition and Medicinal Chemistry, 2018-01) Maciel, Bruna Leal Lima; Medeiros, Amanda Fernandes de; Costa, Izael de Sousa; Carvalho, Fabiana Maria Coimbra de; Kiyota, Sumika; Souza, Beatriz Blenda Pinheiro de; Sifuentes, Daniel Nogoceke; Serquiz, Raphael Paschoal; Uchôa, Adriana Ferreira; Santos, Elizeu Antunes dos; Morais, Ana Heloneida de AraújoA trypsin inhibitor isolated from tamarind seed (TTI) has satietogenic effects in animals, increasing the cholecystokinin (CCK) in eutrophy and reducing leptin in obesity. We purified TTI (pTTI), characterised, and observed its effect upon CCK and leptin in obese Wistar rats. By HPLC, and after amplification of resolution, two protein fractions were observed: Fr1 and Fr2, with average mass of [M þ 14H]þ ¼ 19,594,690 Da and [M þ 13H]þ ¼ 19,578,266 Da, respectively. The protein fractions showed 54 and 53 amino acid residues with the same sequence. pTTI presented resistance to temperature and pH variations; IC50 was 2.7 1010mol.L1 and Ki was 2.9 1011mol.L1 . The 2-DE revealed spots with isoelectric points between pH 5 and 6, and one near pH 8. pTTI action on leptin decrease was confirmed. We conclude that pTTI is a Kunitz trypsin inhibitor with possible biotechnological health-related applicationDissertação Caracterização bioquímica do inibidor de tripsina purificado da semente de tamarindo (Tamarindus indica L.) e avaliação do seu efeito na secreção de colecistocinina e leptina em modelo de obesidade experimental(2017-11-03) Medeiros, Amanda Fernandes de; Morais, Ana Heloneida de Araújo; Santos, Elizeu Antunes dos; ; ; ; Aragão, Cicero Flávio Soares; ; Lima, Liziane Maria de;A obesidade é uma das Doenças Crônicas Não Transmissíveis de maior impacto na saúde pública. A semente de tamarindo (Tamarindus indica L.) vem sendo estudada por possuir inibidor de tripsina, e, entre os atributos relacionados a esse inibidor parcialmente purificado (ITT), tem-se a sua relação com a saciedade, por aumentar colecistocinina (CCK) plasmática em animais eutróficos e seu efeito na redução da concentração circulante de leptina em animais com obesidade, entretanto sem aumento plasmático de CCK. Neste estudo, o ITT foi purificado, caracterizado e avaliado quanto às suas propriedades frente aos hormônios CCK e leptina em ratos Wistar com obesidade. Para purificação e caracterização desse inibidor, foram realizados: fracionamento do extrato bruto proteico com sulfato de amônio; cromatografia de afinidade Tripsina-Sepharose; Cromatografia Líquida de Alta Eficiência (HPLC); determinação da massa molecular por MS-ESI; sequenciamento parcial por MALDI-TOF com ISD; ensaio de estabilidade de temperatura e pH; estimativa dos parâmetros de especificidade; eletroforese bidimensional (2-DE) e dosagens de CCK e leptina plasmática, por ELISA, em ratos com obesidade, submetidos à gavagem oral (730 μg/kg) do inibidor de tripsina purificado (ITTp) comparando-os a ratos com obesidade sem tratamento. Desse modo, o ITT purificado por HPLC foi denominado ITTp. Com o refinamento do método, obtiveram-se, com base no ITTp, dois picos proteicos, as frações: Fr 1 e Fr 2. As massas moleculares médias dessas frações proteicas foram de [M+H]+ = 19594,690 Da e de [M+H]+ = 19578,266 Da, respectivamente. Após redução e alquilação, estimou-se a presença de 4 cisteínas para Fr 1 e Fr 2. As sequências parciais obtidas para Fr 1 e Fr 2 foram de 54 e 53 resíduos de aminoácidos identificados e exatamente com a mesma sequência para ambas, sugerindo-se tratar da mesma molécula. O ITTp se mostrou resistente à variação de temperatura até 80ºC, reduzindo cerca de 30% de sua atividade antitríptica quando em 100 ºC, e resistente aos extremos de pH. Para o ITTp estimou-se a IC50 de 2,7 x 10-10 mol.L-1 e a Ki de 2,9 x 10-11 mol.L-1. Na eletroforese bidimensional com ITTp foram revelados pontos isoelétricos entre pH 5 e 6, além de um spot próximo ao pH 8. Dessa forma, foi constatado que se trata de um inibidor de tripsina da família Kunitz. No experimento in vivo foi confirmada a ação de ITTp sobre a redução de leptina plasmática, mas sem efeito sobre CCK em animais com obesidade, como já atestado em estudos prévios com o ITT. A caracterização bioquímica desse inibidor e os seus efeitos sobre CCK e leptina, observados em experimentos in vivo, constituem relatos inéditos e promissores para uma provável aplicação biotecnológica.Artigo Caracterização físico-química de inibidor de tripsina isolado de sementes de tamarindo (Tamarindus indica l.) Nanoencapsuladoem proteína do leite isolada(Brazilian Journal of health Review, 2019) Morais, Ana Heloneida de Araújo; Oliveira, Gerciane Silva de; Costa, Rafael Oliveira de Araújo; Pais, Tatiana dos Santos; Gomes, Ana Francisca Teixeira; Matias, Lídia Leonize Rodrigues; Medeiros, Amanda Fernandes de; Queiroz, Jaluza Luana Carvalho de; Passos, Thaís SouzaIntrodução: O inibidor de tripsina isolado de sementes de tamarindo (Tamarindus indica L.) (ITT) apresenta ação sacietogênica e anti-inflamatória em modelo experimental. Associado a isto, a encapsulação de proteínas bioativas atua promovendo uma melhora e prolongamento da ação destes ativos.Objetivo: Avaliar o nanoencapsulamento deste inibidor em proteína isolada do leite. Metodologia:O inibidor foi extraído das sementes de tamarindo e isolado por meio de cromatografia de afinidade em Tripsina-Sepharose. Posteriormente, foi encapsulado por meio da técnica de nanoprecipitação em solvente orgânico, na proporção ITT: proteína do soro do leite isolada de 1:4 (p/p). As partículas obtidas foram caracterizadas por diferentes métodos físico-químicos e, avaliadas quanto à eficiência de incorporação. Resultados:A micrografia do encapsulado mostrou a formação de nanopartículas esféricas (83.80 nm (5.80)) (figura 01), com tamanhos heterogêneos, corroborando com a difração laser (Índice de Polidispersão de 0.6 (0.080)), sem depressões e, de acordo com a análise de potencial zeta, instáveis e, com tendência a agregação. As análises de Espectroscopia por Transformada de Fourier (figura 2) e Difração de raios X (figura 3), mostraram, respectivamente, a presença de novas interações químicas entre o agente encapsulante e, o ITT, e natureza amorfa, fornecendo assim um indicativo da encapsulação, sendo este reforçado pelo alto percentual de incorporação do ITT (97.34 (5.50) %). Conclusão: A nanoencapsulação do ITT com proteína isolada do leite se mostra uma ferramenta inovadora, constituindo uma possível aplicação biotecnológica deste ativo, aumentando com isto o seu potencial de utilizaçãoArtigo Characterization of novel trypsin inhibitor in raw and toasted peanuts using a simple improved isolation(Acta Chromatographica, 2019-06) Morais, Ana Heloneida de Araújo; Maciel, Bruna Leal Lima; Medeiros, Amanda Fernandes de; Rocha, Maria Gabriela Ferreira; Serquiz, Alexandre Coelho; Machado, Richele Janaína Araújo; Lima, Vanessa Cristina Oliveira; Carvalho, Fabiana Maria Coimbra de; Costa, Izael de Sousa; Santos, Elizeu Antunes dosTrypsin inhibitors have been described in peanuts and their derived industrialized foods, demonstrating diversity and thermoresistance. Given their most varied applications, these enzymatic protease inhibitors have been isolated and characterized for their potential use as bioinsecticides, herbal medicines, or medicines, but it is not simple. There are still no reports in the literature of the isolation and characterization of trypsin inhibitors in cultivar cavalo rosa (CCR) peanut, a common variety in Brazil. However, there are biological activities related to trypsin inhibitors from peanut-derived products. In this study, we isolated and characterized a novel trypsin inhibitor in CCR peanuts (Arachis hypogaea L.) under different processing conditions using a simple improved isolation. Raw and toasted peanut inhibitor was isolated by ammonium sulfate fractionation and trypsin-cyanogen bromide-activated SepharoseW 4B (CNBr-SepharoseW 4B) chromatography. The inhibitors from raw and toasted peanut were called AhTI1 and AhTI2, respectively, with potent anti-trypsin activity. Activity at different temperatures and pH was evaluated, and both samples were similarly stable under tested conditions. Minimum concentration for inhibition to occur (IC50) was 2.78 × 10−10 M and 2.39 × 10−10 M for AhTI1 and AhTI2, and inhibition constant (Ki) was 3.26 × 10−10 M and 1.54 × 10−10 M, respectively, showing non-competitive reversible kinetics. We concluded that AhTI1 and AhTI2 presented highly specific to trypsin and stable to toasting, different temperatures, and pH ranging. These are important characteristics in the process of developing bioinsecticides or biopharmaceuticals. Thus, this may be an interesting molecule, aiming at its biotechnological application, and it was obtained using a simple and easy isolation processArtigo Characterization of novel trypsin inhibitor in raw and toasted peanuts using a simple improved isolation(Acta Chromatographica, 2019-06) Maciel, Bruna Leal Lima; Medeiros, Amanda Fernandes de; Rocha, Maria Gabriela Ferreira; Serquiz, Alexandre Coelho; Machado, Richele Janaína Araújo; Lima, Vanessa Cristina Oliveira; Carvalho, Fabiana Maria Coimbra de; Costa, Izael de Sousa; Santos, Elizeu Antunes dos; Morais, Ana Heloneida de AraújoTrypsin inhibitors have been described in peanuts and their derived industrialized foods, demonstrating diversity and thermoresistance. Given their most varied applications, these enzymatic protease inhibitors have been isolated and characterized for their potential use as bioinsecticides, herbal medicines, or medicines, but it is not simple. There are still no reports in the literature of the isolation and characterization of trypsin inhibitors in cultivar cavalo rosa (CCR) peanut, a common variety in Brazil. However, there are biological activities related to trypsin inhibitors from peanut-derived products. In this study, we isolated and characterized a novel trypsin inhibitor in CCR peanuts (Arachis hypogaea L.) under different processing conditions using a simple improved isolation. Raw and toasted peanut inhibitor was isolated by ammonium sulfate fractionation and trypsin-cyanogen bromide-activated SepharoseW 4B (CNBr-SepharoseW 4B) chromatography. The inhibitors from raw and toasted peanut were called AhTI1 and AhTI2, respectively, with potent anti-trypsin activity. Activity at different temperatures and pH was evaluated, and both samples were similarly stable under tested conditions. Minimum concentration for inhibition to occur (IC50) was 2.78 × 10−10 M and 2.39 × 10−10 M for AhTI1 and AhTI2, and inhibition constant (Ki) was 3.26 × 10−10 M and 1.54 × 10−10 M, respectively, showing non-competitive reversible kinetics. We concluded that AhTI1 and AhTI2 presented highly specific to trypsin and stable to toasting, different temperatures, and pH ranging. These are important characteristics in the process of developing bioinsecticides or biopharmaceuticals. Thus, this may be an interesting molecule, aiming at its biotechnological application, and it was obtained using a simple and easy isolation processArtigo Chitosan-whey protein nanoparticles improve encapsulation efficiency and stability of a trypsin inhibitor isolated from tamarindus indica L(Food Hydrocolloids, 2018-11) Maciel, Bruna Leal Lima; Queiroz, Jaluza Luana Carvalho de; Costa, Rafael Oliveira de Araújo; Matias, Lídia Leonize Rodrigues; Medeiros, Amanda Fernandes de; Gomes, Ana Francisca Teixeira; Pais, Tatiana dos Santos; Passos, Thais Souza; Santos, Elizeu Antunes dos; Morais, Ana Heloneida de AraújoStudies have shown that the trypsin inhibitor isolated from tamarind seeds (Tamarindus indica L.) (TTI) has satietogenic and anti-inflammatory actions in an experimental model. Aiming to increase the efficiency and stability of its antitriptic activity, the single and conjugated effect of chitosan and whey protein isolate on the incorporation, activity, and stability of TTI was investigated. The particles were obtained by nanoprecipitation technique, evaluated for the efficiency of incorporation and characterized by physical-chemical methods, determination of the amount of inhibitor that reduces the antitriptic activity in 50% (IC50) and, stability in different temperatures and pH. The combination of chitosan and whey protein isolate formed spherical nanoparticles (109 nm), promoted a reduction in IC50 (0.05 mg) compared to pure TTI (0.21 mg), and preserved the inhibitory activity up to 80 °C [35.0% (3.74)] compared to other formulations and TTI [0.0 (0.00)]. In addition, nanoparticles presented stability to the different pH conditions. Thus, the combination of encapsulating agents showed an important strategy to improve the function and stability of TTIArtigo Determinação da atividade antitríptica em proteínas de produtos do amendoim isoladas por cromatografia de afinidade(Quimica Nova, 2014) Morais, Ana Heloneida de Araújo; Araújo, Jéssica Morais de; Alves, Jussara Cristina; Peixoto, Thayane Kerbele Oliveira das Neves; Medeiros, Amanda Fernandes de; Machado, Richele Janaína de Araújo; Serquiz, Alexandre Coelho; Neves, Renata Alexandra Moreira das; Santos, Elizeu Antunes dos; Uchôa, Adriana FerreiraThe peanut is an oleaginous plant of high nutritional value, a source of protein and a trypsin inhibitor. Trypsin inhibitors are proteins present in the vegetable kingdom, considered anti-nutritional factors for animals. However, there have been several recent reports about their heterologous and beneficial effects on human health. These important effects have been the focus of studies investigating these inhibitors in foods. The aim of the present study was to isolate and determine the estimated molecular mass and specific inhibitory activity, for trypsin in the Japanese peanut, peanut butter, and peanut nougat using the techniques of precipitation with ammonium sulfate and affinity chromatography on trypsin - Sepharose CNBr 4B. The techniques used in this study were efficient for isolating the protein inhibitors with antitryptic specific activity of 694 UI mg-1, 823 UI mg-1 and 108 UI mg-1 for the Japanese peanut, peanut nougat, and peanut butter, respectively. The techniques featured high selectivity of the adsorbent, with consequent efficiency in isolation, given the low amount of dosed proteins and specific antitryptic activity presented by the products studied. The various health-related benefits show the importance of detecting and isolating efficient trypsin inhibitors in foods, taking into account the health claims attributed to the vegetable and its high consumption by humansTCC Dieta de cafeteria e seu impacto em parâmetros bioquímicos preditivos da síndrome metabólica em modelo experimental(Universidade Federal do Rio Grande do Norte, 2016-09-30) Santos, Janaína Henrique dos; Morais, Ana Heloneida de Araújo; Amanda Fernandes de Medeiros; Morais, Ana Heloneida de Araújo; Medeiros, Amanda Fernandes de; Machado, Richele Janaína de AraújoA chamada transição nutricional se caracteriza por mudanças ocorridas no perfil alimentar da população, resultante da associação entre diminuição da prática de atividade física e alterações no padrão dietético, que apontam um aumento do consumo de gorduras, principalmente saturadas, açúcar e alimentos refinados, e pela redução do consumo de carboidratos complexos e de fibras, esse fenômeno acaba provocando impactos à saúde por favorecer o estabelecimento das DCNT. Buscando uma maior compreensão do perfil nutricional atual e seus efeitos a longo prazo, estudos têm sido realizados utilizando as chamadas dietas de cafeteria, que consistem, em sua maioria, em uma alimentação rica em gorduras e açúcares, portanto, se assemelhando aos hábitos alimentares da sociedade ocidental. O grupo de pesquisa NutriSBioativoS desenvolveu uma dieta de cafeteria que apresentou, no estudo de Santos (2016), uma tendência em alterar a glicemia de jejum de ratos. Com base nesse fato o presente estudo objetiva avaliar o efeito de uma dieta de cafeteria sobre os outros parâmetros bioquímicos preditivos do diagnóstico da SM em modelo experimental. Para tanto, a dieta de cafeteria foi produzida e oferecida a dois grupos de animais (n = 05 por grupo; ratos Wistar, machos, adultos) por 17 semanas e ao final do experimento foram analisados os níveis de TG e HDL-c. A análise estatística revelou que os ratos alimentados com a dieta de cafeteria apresentaram níveis de TG significativamente maiores do que aqueles alimentados com dieta padrão (p = 0,0079). Os níveis de HDL-c para os animais submetidos à dieta de cafeteria em comparação com o grupo da dieta padrão não apresentaram diferença significativa (p = 0.7937). Diante dos resultados obtidos é possível concluir que a dieta de cafeteria desenvolvida pelo nosso grupo de pesquisa é responsável por alterar os níveis de TG, um importante parâmetro envolvido no diagnóstico da SM. Dadas as suas características nutricionais e o impacto causado à saúde, a dieta pode vir a ser utilizada em estudos posteriores, a fim de investigar, de forma mais aprofundada, seu papel no desenvolvimento das DCNT.Artigo Hydrolyzed proteins and vegetable peptides: anti-Inflammatory mechanisms in obesity and potential therapeutic targets(Nutrients, 2022) Medeiros, Amanda Fernandes de; Queiroz, Jaluza Luana Carvalho de; Maciel, Bruna Leal Lima; Morais, Ana Heloneida de Araújo; https://orcid.org/0000-0002-6460-911XChronic low-grade inflammation is present in overweight and obesity, causing changes in several metabolic pathways. It impairs systemic functioning and positively feeds back the accumula tion of more adipose tissue. Studies with hydrolyzed proteins and plant peptides have demonstrated a potential anti-inflammatory and immunomodulatory effect of these peptides. However, it is chal lenging and necessary to explore the mechanism of action of such molecules because understanding their effects depends on their structural characterizations. Furthermore, the structure might also give insights into safety, efficacy and efficiency, with a view of a possible health application. Thus, the present narrative review aimed to discuss the mechanisms of action of hydrolyzed proteins and plant peptides as anti-inflammatory agents in obesity. Keywords and related terms were inserted into databases for the search. Based on the studies evaluated, these biomolecules act by different pathways, favoring the reduction of inflammatory cytokines and adipokines and the polarization of macrophages to the M2 phenotype. Finally, as a future perspective, bioinformatics is suggested as a tool to help understand and better use these molecules considering their applicability in pre-clinical and clinical studies.Artigo Mechanism of the action of bioactive proteins of vegetables in diabetes mellitus type 2: systematic review protocol(Medicine, 2019) Morais, Ana Heloneida de Araujo; Medeiros, Amanda Fernandes de; Costa, Izael de Sousa; Piuvezam, Grasiela; Medeiros, Gidyenne Christine Bandeira Silva de; Maciel, Bruna Leal Lima; https://orcid.org/0000-0002-6460-911XBackground: Diabetes mellitus type 2 (DM2) is a chronic disease of significant prevalence causing hyperglycemia and several comorbidities. Evidences highlight the performance of non - protein bioactive compounds found in vegetables in the control of hyperglycemia. This study describes a protocol of a systematic review, which analyzes the action of proteins and bioactive peptides of plants in DM2. Methods: The Preferred Reporting Items guide this protocol for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P) was used. The databases that will be used for searching will be PubMed, ScienceDirect, Scopus, Web of Science, EMBASE, and Virtual Health Library, Brazil (VHL). Studies that use bioactive proteins and peptides of vegetal origin in DM2 will be included in the systematic review. The studies will be identified using clinical parameters and the effect on insulin resistance. The characteristics of the studies as control groups, test substance, dosage, intervention time, and the main results will be described. Selection of studies, data extraction, and methodological quality assessment will be performed independently by two experienced reviewers. Results: This protocol will be the basis for a systematic review identifying the mechanism of action of plant proteins and peptides in type 2 diabetes mellitus. Conclusion: Systematic reviews from this protocol will provide support for the construction of researches that analyze the effect of plant bioactive proteins and peptides on the control of hyperglycemia and how these molecules act in the control of DM2Artigo Prospecting native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds(Elsevier, 2023) Morais, Ana Heloneida de Araújo; Luz, Anna Beatriz Santana; Medeiros, Amanda Fernandes de; Bezerra, Lucas Lima; Lima, Mayara Santa Rosa; Pereira, Annemberg Salvino; Silva, Emilly Guedes Oliveira e; Passos, Thais Souza; Monteiro, Norberto de Kassio Vieira; https://orcid.org/0000-0002-6460-911XThe study aimed to prospect in silico native and analogous peptides with anti-SARS CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds (TTIp). From the most stable theoretical model of TTIp (TTIp 56/287), in silico cleavage was performed for the theoretical identification of native peptides and generation of analogous peptides. The anti SARS-CoV-2 potential was investigated through molecular dynamics (MD) simulation between the peptides and binding sites of transmembrane serine protease 2 (TMPRSS2), responsible for the entry of SARS-CoV-2 into the host cell. Five native and analogous peptides were obtained and validated through chemical and physical parameters. The best interaction potential energy (IPE) occurred between TMPRSS2 and one of the native peptides obtained by cleavage with trypsin and its analogous peptide. Thus, both peptides showed many hydrophobic residues, a common physical–chemical property among the peptides that inhibit the entry of enveloped viruses, such as SARS-CoV-2, present in specific drugs to treat COVID-19Artigo Satietogenic protein from tamarind seeds decreases food intake, leptin plasma and CCK-1r gene expression in obese wistar rats(Obesity Facts, 2018) Maciel, Bruna Leal Lima; Costa, Izael De Souza; Medeiros, Amanda Fernandes de; Carvalho, Fabiana Maria Coimbra de; Lima, Vanessa Cristina Oliveira de; Serquiz, Raphael Paschoal; Serquiz, Alexandre Coelho; Silbiger, Vivian Nogueira; Bortolin, Raul Hernandes; Santos, Elizeu Antunes dosObjective: This study evaluated the effect of a protein, the isolated Trypsin Inhibitor (TTI) from Tamarindus indica L. seed, as a CCK secretagogue and its action upon food intake and leptin in obese Wistar rats. Methods: Three groups of obese rats were fed 10 days one of the following diets: Standard diet (Labina®) + water; High Glycemic Index and Load (HGLI) diet + water or HGLI diet + TTI. Lean animals were fed the standard diet for the 10 days. Food intake, zoometric measurements, plasma CCK, plasma leptin, relative mRNA expression of intestinal CCK-related genes, and expression of the ob gene in subcutaneous adipose tissue were assessed. Results: TTI decreased food intake but did not increase plasma CCK in obese animals. On the other hand, TTI treatment decreased CCK-1R gene expression in obese animals compared with the obese group with no treatment (p = 0.027). Obese animals treated with TTI presented lower plasma leptin than the non-treated obese animals. Conclusion: We suggest that TTI by decreasing plasma leptin may improve CCK action, regardless of its increase in plasma from obese rats, since food intake was lowestArtigo Structural insights and molecular dynamics into the inhibitory mechanism of a kunitz-type trypsin inhibitor from tamarindus indica L(Journal of Enzyme Inhibition and Medicinal Chemistry, 2021-01) Maciel, Bruna Leal Lima; Medeiros, Amanda Fernandes de; Souza, Beatriz Blenda Pinheiro de; Coutinho, Lucas Pinheiro; Murad, Aline Melro; Santos, Paula Ivani Medeiros dos; Monteiro, Norberto de Kássio Vieira; Santos, Elizeu Antunes dos; Morais, Ana Heloneida de AraújoTrypsin inhibitors from tamarind seed have been studied in vitro and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced de novo by MALDI-TOF/ TOF, performed its homology modelling, and assessed the interaction with the trypsin enzyme through molecular dynamics (MD) simulation under physiological conditions. We identified additional 75 amino acid residues, reaching approximately 72% of total coverage. The four best conformations of the best homology modelling were submitted to the MD. The conformation n287 was selected considering the RMSD analysis and interaction energy (–301.0128 kcal.mol1 ). Residues Ile (54), Pro (57), Arg (59), Arg (63), and Glu (78) of pTTI presented the highest interactions with trypsin, and arginine residues were mainly involved in its binding mechanism. The results favour bioprospecting of this protein for pharmaceutical health applicationsArtigo A trypsin Inhibitor from tamarind reduces food intake and improves inflammatory status in rats with metabolic syndrome regardless of weight loss(Nutrients, 2016-09) Maciel, Bruna Leal Lima; Carvalho, Fabiana Maria Coimbra de; Lima, Vanessa Cristina Oliveira de; Costa, Izael de Souza; Medeiros, Amanda Fernandes de; Serquiz, Alexandre Coelho; Lima, Maíra Conceição Jerônimo de Souza; Serquiz, Raphael Paschoal; Uchôa, Adriana Ferreira; Santos, Elizeu Antunes dos; Morais, Ana Heloneida de AraújoTrypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL) and triglycerides (TG) (Kruskal–Wallis, p < 0.05). Interleukin-6 (IL-6) production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α) was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatmentArtigo What are the mechanisms of action of anti-inflammatory agents in adipose tissue? a protocol for systematic review and meta-analysis(Medicine, 2021) Morais, Ana Heloneida de Araujo; Nascimento, Sara Sayonara da Cruz; Queiroz, Jaluza Luana Carvalho de; Medeiros, Amanda Fernandes de; Nunes, Ana Clara de França; Piuvezam, Grasiela; Maciel, Bruna Leal Lima; Passos, Thaís Souza; https://orcid.org/0000-0002-6460-911XBackground: Obesity is a disease characterized by the abnormal accumulation of adipose tissue in the body, triggering a chronic subclinical state of inflammation. Bioactive compounds, given their anti-inflammatory properties, are a safe and promising alternative in controlling the inflammatory condition of obesity. This study describes a systematic review protocol aiming to analyze the anti inflammatory molecules mechanisms and compounds action on adipocytes. Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) will outline the protocol and PRISMA to the systematic review. The databases used for research will be PubMed, Science Direct, Scopus, Web of Science, BVS, and EMBASE. Experimental studies performed on rats and mice with a control group that describes treatment with anti-inflammatory agents (drugs, nutraceuticals, bio active compounds, among others) at any frequency, time, and dose will be included. Three independent reviewers will select studies and extract data. The evaluation of the methodological quality of each research will be performed using the SYRCLE tool. If at least 2 studies show clinical and/or methodological and/or statistical homogeneity, a meta analysis will be performed, using the RevMan Analyzes statistical package in Review Manager v.5.3. Results: In this study, we hope to find a considerable number of articles presenting mechanisms involved in the action of anti inflammatory molecules and compounds on adipocytes. Conclusion: The systematic review produced from this protocol will present evidence on the mechanisms involved in the action of anti-inflammatory molecules and compounds in adipocytes. It will also contribute to developing new research and new insights about anti-inflammatory therapies with a future application view. Record of systematic review: This review was registered with the International Register of Prospective Systematic Reviews on May 18, 2020 (registration: CRD42020182897). Available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID= CRD42020182897. Abbreviations: 5-LOX = enzyme 5-lipoxygenase, AMPK = AMP-activated protein kinase, BAT = brown adipose tissue, CAPES = Coordination of Improvement of Higher Education Personnel, CNPq = National Council for Scientific and Technological Development, COX-2 = enzyme cyclooxygenase, IL-6 = Interleukin-6, iNOS = nitric oxide-synthase induced, NF-kB = factor kappa B, Nrf2 = nuclear factor erythroid 2-related factor 2, PICOS = population, interventions, control, and study results, PPAR-g = peroxisome proliferator-activated receptor gamma, PRISMA = Preferred Reporting Items for Systematic Reviews and Meta Analyses, PRISMA-P = Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols, PROSPERO = International Prospective Register of Systematic Reviews, SREBP-1c = sterol regulatory element-binding protein 1, Syrcle = Systematic Review Center for Laboratory Animal Experimentation, TLR = Toll-like receptors, TNF-a = Tumor Necrosis Factor alpha, WAT = white adipose tissue, WHO = World Health Organization.