https://repositorio.ufba.br/handle/ri/21446 2026-04-17T16:32:05Z https://repositorio.ufba.br/handle/ri/43561 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 2025-11-03T00:00:00Z https://repositorio.ufba.br/handle/ri/42696 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 0006-06-17T00:00:00Z https://repositorio.ufba.br/handle/ri/37343 Título: Caracterização molecular dos genótipos C, F1 e BC do Vírus da Imunodeficiência Humana tipo 1 (HIV-1) circulantes na região Nordeste do Brasil - análise da dispersão e história evolutiva. Autor(es): Oliveira, Rodrigo Cunha Primeiro Orientador: Cunha, Joana Paixão Monteiro Abstract: INTRODUCTION: The Human Immunodeficiency Virus (HIV) is the etiological agent of the Acquired Immunodeficiency Syndrome (AIDS), a without a vaccine or cure. HIV-1 presents an extensive genetic variability and in Brazil, subtypes B, C and subsubtype F1 are the prevalent genotypes and intersubtype recombinants such as BC and BF1 are also detected. Non-B subtypes have increased in frequency in Brazil. OBJECTIVE: To identify non-B viral isolates of HIV-1 (subtype C, subsubtype F1 and BC recombinant) in Bahia and to analyze the dispersion route and genotypic and molecular characteristics. MATERIAL AND METHODS: Whole blood samples was collected from patients with HIV-1 followed up at the Professor Edgard Santos University Hospital. The genomic DNA was extracted and sequenced by the Sanger method. The genomes were assembled using the GENEIOUS software. Reference alignments were generated for molecular and phylogenetic analyzes from sequences available in the Los Alamos database and were analyzed through Bioinformatic softwares. RESULTS: Through the obtaining whole blood samples 5 subtype C sequences, 19 BF1 and F1 sequences and 1 BC recombinant sequences were obtained. The phylodynamic analyzes estimated that the F1 sub-subtype reached the Brazilian territory around the 70's. The C subtype reached the Northeast region around 1985, from the South, Southeast and Central-west regions, and the C strain found in Bahia descends from the lineage of the South region. The BC sample from our cohort showed a common recombination point to other Brazilian recombinants. The genetic characterization of BC genomes reveals a preferential recombination point with the B fragment conserved in pol, env and nef genes. The molecular characterization of near-full length genome of local and global subtype C suggests that the most of strain has a low replicative capacity. CONCLUSIONS: The F1 Brazilian isolates belongs to a single lineage, which descends from the Central-West of the Africa. The subtype C found in the Northeast region and state of Bahia descends from the South region, circulating in the region since 1985. The new pattern of BC sequence may represent a new CRF in Brazil. The genomic analyzes results of recombinant BC strains reveal that characteristics of subtype B maintained in BC strains may favor adaptative advantages. Concerning the pure C genotype, the amino acid and molecular characteristics pointing to a favor this subtype transmission. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Tese 2023-06-12T00:00:00Z https://repositorio.ufba.br/handle/ri/36020 Título: Qualidade de sementes de Ricinus communis L. submetidas ao envelhecimento: perfil metabolômico, transcriptômico, enzimático e fisiológico Autor(es): Jesus, Thamires Soares Ricardo Primeiro Orientador: Fernandez, Luzimar Gonzaga Abstract: To assess seed vigor, it is possible to perform accelerated aging (AA), which consists of submitting the seeds to high temperature and humidity. In addition, this test makes it possible to evaluate the behavior of seeds at a physiological, biochemical and molecular level. The objective of this study was to evaluate the behavior of seeds of cultivars BRS 188 Paraguaçu and BRS 149 Nordestina of Ricinus communis L. before and after being submitted to AA regarding the metabolomic, transcriptomic, enzymatic and physiological profile. The following analyzes were carried out: initial characterization of seeds, AA standardization, seed moisture contente, germination test, determination of electrical conductivity and pH exudate, tetrazolium test, lipid peroxidation (malonaldehyde levels - MDA), determination of the activities of antioxidant enzymes (superoxide dismutase – SOD, catalase – CAT, ascorbate peroxidase – APX, monodehydroascorbate reductase – MDHAR, dehydroascorbate reductase – DHAR, glutathione reductase – GR, glutathione peroxidase – GPX and glutathione S-transferase – GST). The evaluation of primary and secondary metabolites by metabolomics, and the production of transcripts through the RNA-seq test for the seeds of BRS 188 Paraguaçu. In the BRS 188 Paraguaçu seeds after the AA, there was a loss of vigor, increase in electrical conductivity, alteration in the production of primary (galactinol, myo-inossitol, melibiose, glyoxylic acid, sorbitol, inositol, xylose, sucrose and ribitol) and secondary metabolites of the terpene, phenolic and alkaloid classes, and greater gene expression, especially energy metabolismo. In response to AA, the increase in MDA concentration and APX and CAT activity was only significant in the whole seed, while SOD and DHAR were enzymes that showed a significant increase in activity in the whole seed and in the embryo. The change in GST and GPX activity was significant only in embryo samples. The cultivar BRS 149 Nordestina, showed after AA a significant reduction in viability, with membrane damage and increased lipid peroxidation. The increase in SOD activity, APX and DHAR were significant in whole seeds and the embryo, while CAT activity in the whole seed. MDHAR, GR and GPX, activity increased significantly only in the embryo. When analyzing the physiological, biochemical and molecular mechanisms of seeds after AE, that MDA, SOD and DHAR, and the increase of electrolytes in the exudate are biochemical biomarkers for the evaluation of seed quality, even as, the genes important for energy metabolism are suitable biomarkers for evaluating the quality of seeds of this species. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Tese 2022-03-04T00:00:00Z