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Investigação do potencial terapêutico da Lepidium meyenii (maca) e macamidas sintéticas: avaliação das atividades citotóxica e neuroprotetora

Mon, 03 Nov 2025 00:00:00 GMT

Título: Investigação do potencial terapêutico da Lepidium meyenii (maca) e macamidas sintéticas: avaliação das atividades citotóxica e neuroprotetora Autor(es): Carvalho, Fernanda Vidal Primeiro Orientador: Jesus, Paulo Roberto Ribeiro de Abstract: Introduction: Lepidium meyenii (maca) is a plant with diverse biological activities, including antioxidant, cytotoxic, and anti-inflammatory properties. Among its metabolites, macamides stand out as potential antitumor’ and neuroprotective compounds. Glioblastoma (GBM) and Parkinson's disease (PD), two central nervous system (CNS) pathologies, have unfavorable prognoses and limited therapeutic options, representing relevant targets for new compounds. Objective: This study aimed to evaluate the antitumor potential of fractions of the crude extract of maca root and identify its bioactive compounds, as well as to investigate the antitumor and neuroprotective potential of synthetic macamides. Methodology: The crude extract of maca root underwent bioguided fractionation to assess the cytotoxicity of the fractions, which was tested on rat glioma cells (C6). The metabolomic profile of the fractions was characterized by UHPLC-Q-TOF-MS/MS and correlated with biological activity by chemometric analysis. In parallel, macamides were synthesized and their antitumor activity was evaluated in multiple glioma and GBM cell lines (C6, U87, U343, GL15) and in primary astrocyte cultures using the MTT assay. Cell migration (scratch assay), cell cycle (flow cytometry), and PI3K/AKT and STAT3 signaling pathways (Western blotting) were investigated in U87 cells. The cytotoxic effect of macamides on U87 and U343 spheroids was assessed by analyzing cell viability (MTT assay) and morphological changes. Neuroprotective activity was evaluated in cellular models of PD using SH-SY5Y and PC12 cells treated with the neurotoxins salsolinol and dopamine, respectively. Results and discussion: Maca extract fractions reduced the viability of C6 cells (200 μg/mL), and from the metabolomic analysis, the main bioactive compounds correlated with this cytotoxicity were the polyunsaturated fatty acids 9-oxo-10E,12E-octadecadienoic and linolenic acids, in addition to macamide B. Macamides (5-100 μM) demonstrated potent cytotoxicity against all GBM cell lines tested, with high selectivity, since they did not affect astrocyte viability. Furthermore, macamides inhibited the migration of U87 cells, induced cell cycle arrest in the G0/G1 phase, and inhibited the PI3K/AKT and STAT3 signaling pathways. The cytotoxic effect was also confirmed in spheroid models by reducing cell viability and altering morphological integrity. In the context of PD, macamides protected SH-SY5Y cells from salsolinol-induced neurotoxicity, but showed no protective effect on dopamine-treated PC12 cells. Conclusion: Taken together, the results demonstrate that macamides are key bioactive metabolites of maca, exhibiting dual therapeutic potential. Their ability to selectively induce GBM cell death by inhibiting crucial signaling pathways and exhibiting neuroprotective effects positions them as promising compounds for the development of new therapies for CNS diseases. Editora / Evento / Instituição: UNIVERSIDADE FEDERAL DA BAHIA Tipo: Tese

Rutina previne neurotoxicidade e alterações comportamentais em modelo animal de degeneração dopaminérgica induzido por aminocromo

Thu, 17 Jun 0006 00:00:00 GMT

Título: Rutina previne neurotoxicidade e alterações comportamentais em modelo animal de degeneração dopaminérgica induzido por aminocromo Autor(es): Souza, Jéssica Teles Primeiro Orientador: Silva, Victor Diogenes Amaral da Abstract: Aminochrome is a compound produced in dopaminergic neurons during neuromelanin formation, with the potential to induce oxidative stress, alpha-synuclein accumulation, and neuroinflammation, resembling the pathophysiology of Parkinson’s disease (PD). Despite advances in understanding the disease’s pathophysiological mechanisms, PD remains incurable, as the gold-standard treatment, L-DOPA, is unable to halt or mitigate the neurodegenerative process. Rutin, a flavonoid with well-documented anti-inflammatory, antioxidant, and neurogenic properties, has been recognized in the literature. Thus, this study aims to investigate the behavioral and neuroprotective effects of rutin in an in vivo PD model induced by aminochrome. To this end, male Wistar rats (270–330 g) (CEUA-ICS, Protocol No. 3006070223) were divided into four groups: control (CTR), 10 mg/kg rutin (RUT), 6 nmol aminochrome (AMI), and aminochrome + rutin (AMI + RUT). The rats underwent stereotaxic surgery for aminochrome injection into the striatum. Animals in the RUT and AMI + RUT groups received daily oral doses of rutin for 21 days. All animals were subjected to behavioral tests on the 14th day. Midbrain and striatal samples were collected on the 22nd day and fixed with 4% paraformaldehyde for immunohistochemistry (TH and SOX-10) and immunofluorescence (GFAP, S100B, IBA-1, and TH). The open-field test revealed a reduction in the total frequency of rearing and grooming in the AMI group compared to the CTR group. The elevated plus-maze test showed that AMI group animals navigated the apparatus less and exhibited fewer entries into the open arms compared to the CTR group. Immunohistochemical quantification of TH+ cells confirmed reduced cell viability induced by aminochrome at the level of the third cranial nerve pair in the substantia nigra pars compacta (SNpc). Furthermore, the AMI group displayed an increase in IBA1+ cells and microglia-neuron interactions compared to the CTR group. Colocalized expression of GFAP+ and S100B+ was also higher in the AMI group compared to the CTR and AMI + RUT groups. Quantification of SOX10+ cells showed no significant changes. Collectively, these findings demonstrate that striatal aminochrome injection induces pronounced degeneration in the medial SNpc, accompanied by glial reactivity, neuroinflammation, and anxiogenic behavioral changes. These effects were prevented by enteral rutin treatment. The behavioral consequences of unilateral aminochrome lesions in the striatum had not been well described previously; thus, this study contributes to the characterization of a novel PD model and elucidates the therapeutic potential of rutin in the disease. Editora / Evento / Instituição: UNIVERSIDADE FEDERAL DA BAHIA Tipo: Tese

Avaliação in silico do potencial inibitório de terpenos de Ricinus communis L. sobre a MPro de SARS-CoV-2

Thu, 13 Mar 2025 00:00:00 GMT

Título: Avaliação in silico do potencial inibitório de terpenos de Ricinus communis L. sobre a MPro de SARS-CoV-2 Autor(es): Rocha, Thereza Christina Teixeira Primeiro Orientador: Fernandez, Luzimar Gonzaga Abstract: The SARS-CoV-2 virus, which causes COVID-19, is responsible for a highly contagious disease that can result in severe symptoms in humans. Various strategies have been proposed to combat COVID-19, with one promising approach being the inhibition of the main protease known as MPro (3CLpro). This protease plays a crucial role in viral replication and is both highly conserved and specific among coronaviruses, making it a key target for developing effective inhibitors. Ricinus communis L., commonly known as the castor bean plant, is an oil-rich species that belongs to the Euphorbiaceae family. It has diverse applications in both medical and industrial fields, highlighting its significant socioeconomic value in Brazil. To explore bioactive compounds derived from Brazil's native biodiversity for potential COVID-19 treatments, this study investigated the interactions between 34 terpenes from R. communis and MPro using an in silico methodology that combines Docking and Molecular Dynamics (MD) simulations. Docking analyses were conducted at the active site of MPro and were validated through redocking, cross-docking, correlations with biological activity, and decoys. These analyses were performed using software tools such as AutoDock 4.2, AutoDock Vina, DockThor, and GOLD, utilizing scoring functions like PLP, Goldscore, Chemscore, and ASP to elucidate the primary interactions between the R. communis terpenes and MPro. Based on the Lipinski Rule (Ro5) and efficiency metrics (LE, LLE, and FQ) calculated for each terpene, the five highest-ranked compounds- camphor, 1,8-cineole, α-thujone, ficusic acid, and 6α-hydroxy-10β-methoxy-7α,8α-epoxy-5-oxocasban-20-10-olide- were selected for subsequent MD studies. Following MD analyses, it was determined that among the selected terpenes, ficusic acid (LLE = 3.54, molecular mass = 196 g/mol, RMSD = 3.50 Å) and 6α-hydroxy-10β-methoxy-7α,8α-epoxy-5-oxocasban-20-10-olide (LLE = 3.50, molecular mass = 376 g/mol, RMSD = 9.94 Å) demonstrated noteworthy inhibitory potential against SARS-CoV-2 MPro. Notably, the interactions of these compounds with MPro have not been reported in the literature before, emphasizing their novelty. These findings highlight ficusic acid and 6α-hydroxy-10β-methoxy-7α,8α-epoxy-5-oxocasban-20-10-olide as promising candidates for future in vitro and in vivo studies aimed to treat COVID-19. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação

Perfil transcriptômico dinâmico do leite materno maduro e os impactos bioquímicos no desenvolvimento infantil: uma análise in sílico

Tue, 11 Mar 2025 00:00:00 GMT

Título: Perfil transcriptômico dinâmico do leite materno maduro e os impactos bioquímicos no desenvolvimento infantil: uma análise in sílico Autor(es): Nobrega, Alessandra Santana Primeiro Orientador: Macambira, Simone Garcia Abstract: INTRODUCTION: Breast milk is a mammary glands product of high complexity and specificity, that has a direct impact on the development of human beings. However, despite its significant role, there is still limited information available, especially when it comes to mature milk where little has been discussed about its composition over the years. Among various components present in milk, emerging studies demonstrate that the presence of RNAs in milk is a key component to be evaluated. Therefore, this study performed an analysis based on available public databases of the RNA present in mature milk samples at different periods of time, to define its profile and its variations over time. The hypothesis is that mature breast milk has specific potentialities, according to the degree of maturation that justifies continued breastfeeding. METHODOLOGY: Public transcriptome data from GEODATASET, with accession codes GSE192543 and GSE75726, were analyzed. Available samples were examined using bioinformatics tools through the Galaxy platform. Subsequently, filtering was performed based on the ratio between expression level by Log Fold Change and the p-value <0.05, to identify differentially expressed RNAs between the mature breast milk samples of 01, 02, 04 and 06 months. RESULTS: After data processing, it was possible to find a dynamic gene regulation of the transcripts: being negative in the first months, but positive from the sixth month of lactation; indicating that mature milk is heterogeneous. The presence of these genes, proteins, enzymes and cellular elements in mature breast milk allows the promotion of additional support to the neural, metabolic and immunological development of the still immature infant organism; and elucidates the correlational statistics of health and disease states with the positive practice of breastfeeding. CONCLUSIONS: The components found in mature breast milk samples change to support the diverse biological needs of the infant, providing a responsive cellular environment of increasing complexity. Further studies are necessary to continue the analysis of maternal milk dynamics and its properties after 6 months so that we can establish its long-term behavior. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação