https://tedebc.ufma.br/jspui/handle/tede/1 Tue, 15 Sep 2026 09:23:52 GMT 2026-09-15T09:23:52Z http://tede2.ufma.br:8080/jspui/retrieve/1/RENORBIOIMG1.png https://tedebc.ufma.br/jspui/handle/tede/1 https://tedebc.ufma.br/jspui/handle/tede/7235 Título: Bioprospecção do extrato das folhas de Fridericia Platyphylla na cardioprevenção em roedores e obtenção de bioprodutos Autor: FERREIRA, Andressa Coelho Primeiro orientador: RIBEIRO, Rachel Melo Abstract: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, encompassing conditions such as coronary artery disease, systemic arterial hypertension, and acute myocardial infarction (AMI), which is characterized by coronary artery obstruction and subsequent cardiomyocyte death. In this context, this thesis was designed to integrate technological prospection, scientific review, and experimental investigation regarding the therapeutic potential of Fridericia platyphylla (Cham.) L. G. Lohmann. Initially, a technological prospection study was conducted based on the analysis of patent applications deposited in major national and international databases, including INPI, Espacenet, Google Patents, Derwent Innovations Index, and WIPO, considering filings from the past 15 years and using descriptors related to the species and its botanical synonym Arrabidaea brachypoda, combined with terms associated with cardiovascular diseases. In parallel, an integrative literature review was performed through systematic searches in PubMed, SciELO, and Google Scholar, covering studies published between October 2014 and December 2024, including in vivo, in vitro, and ethnopharmacological investigations. Additionally, an experimental study was developed using the hydroethanolic extract of Fridericia platyphylla (FPE), obtained and chemically characterized by advanced chromatographic techniques. Adult male Wistar rats (Rattus norvegicus) were allocated into experimental groups (Control, ISO, FPE50, FPE75, and FPE100) and treated for 15 days, with AMI induced by subcutaneous administration of isoproterenol (85 mg/kg) on days 14 and 15. At the end of the protocol, hemodynamic and electrocardiographic assessments were performed, followed by the collection of biological samples for biochemical, hematological, hemostatic, morphometric, and histopathological analyses (CEUA No. 23115.019856/2023-61). Technological prospection identified 66 patents (2008–2023), predominantly from Brazilian academic institutions, with emphasis on the Universidade Estadual de Campinas, followed by UFMA and UNESP, highlighting the growing scientific and technological interest in the species. The integrative review included 20 studies, demonstrating a diversity of extracts and compounds with relevant biological activities (anti-inflammatory, antioxidant, antiproliferative, antifungal, and antiparasitic), particularly flavonoids such as brachydins and luteolin. In the experimental study, phytochemical characterization of FPE revealed a predominance of glycosylated flavonoids, especially rutin and apigenin. FPE treatment prevented deleterious effects on blood pressure following isoproterenol administration. Moreover, FPE significantly reduced cardiac hypertrophy, infarct size, and biomarkers of myocardial injury, including troponin, CPK, CK-MB, LDH, AST, and C-reactive protein. Improved preservation of hepatic and renal parameters, serum phosphorus levels, electrocardiographic findings, and myocardial architecture was also observed. Furthermore, there was a marked reduction in edema, inflammatory infiltration, erythrocyte extravasation, and myonecrosis, along with decreased collagen deposition, with more pronounced effects in the FPE100 group. Additionally, FPE significantly improved hematological parameters, reducing total leukocyte count and plasma fibrinogen levels, indicating consistent anti-inflammatory and antithrombotic effects. Taken together, the experimental findings, combined with literature evidence and innovation landscape analysis, supported the development of an innovative pharmaceutical composition, culminating in a patent application with potential application in cardiovascular disorders, reinforcing the pharmacological, technological, and translational relevance of the species. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese Wed, 04 Mar 2026 00:00:00 GMT https://tedebc.ufma.br/jspui/handle/tede/7235 2026-03-04T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/7234 Título: Atividade analgésica e anti-inflamatória do ambroxol no tratamento da endometriose: estudo experimental com ratas Wistar Autor: FROTA, Gustavo Medeiros Primeiro orientador: CARTÁGENES, Maria do Socorro de Sousa Abstract: Endometriosis is a chronic inflammatory gynecological disease frequently associated with pelvic pain, infertility, and a significant impact on patients’ quality of life. Despite therapeutic advances, currently available treatments have limitations related to clinical response, symptom recurrence, and adverse effects, highlighting the need for new pharmacological approaches. Structured into two complementary chapters, this thesis aimed to investigate the therapeutic potential of ambroxol in endometriosis by integrating evidence from a bibliometric review and an original experimental study. Initially, a bibliometric analysis of the literature on the pharmacological activities of ambroxol in experimental models was conducted using the Web of Science and Scopus databases. Twenty-four studies published between 1994 and 2023 were included, with the main research areas comprising Medicine (33.3%), Pharmacology (30.6%), Biochemistry (16.7%), and Neuroscience (11.1%). Subsequently, an experimental study was conducted using an animal model of endometriosis, in which ambroxol was orally administered at doses of 10, 50, and 100 mg/kg/day for 21 days. Behavioral parameters of spontaneous pain, mechanical sensitivity, and motor performance were assessed using the Rat Grimace Scale, von Frey test, and rotarod test, respectively. Serum IL-1β levels, peritoneal inflammatory response, endometriotic implant volume, and epithelial integrity were also evaluated. Ambroxol reduced spontaneous pain manifestations and increased the mechanical withdrawal threshold during treatment, while motor performance was preserved. On day 21, serum IL-1β levels were 56.48, 5.01, and 47.65 pg/mL in the groups treated with ambroxol at 10, 50, and 100 mg/kg, respectively, compared with 178.96 pg/mL in the negative control group, with significant reductions in all treated groups. A reduction in the peritoneal inflammatory response was also observed. The 50 and 100 mg/kg doses reduced endometriotic implant volume and promoted histopathological changes characterized by decreased epithelial integrity. Taken together, the findings of this thesis demonstrate analgesic, anti-inflammatory, and structural effects of ambroxol in an experimental model of endometriosis and provide preclinical evidence supporting further investigation of its therapeutic potential in this condition. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese Fri, 10 Jul 2026 00:00:00 GMT https://tedebc.ufma.br/jspui/handle/tede/7234 2026-07-10T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/7231 Título: Prospecção químico-farmacológica do extrato hidroalcoólico das amêndoas de Syagrus cocoides Martius e desenvolvimento de produtos tecnológicos Autor: MOURA, Jhônata Costa Primeiro orientador: RIBEIRO, Rachel Melo Abstract: Systemic Arterial Hypertension (SAH) is one of the leading causes of global morbidity and mortality. Treatment is based on the use of medications and lifestyle changes. Among the groups of antihypertensive drugs used for this purpose, diuretics show good efficacy; however, they are associated with adverse effects and therapeutic failures, which justifies the search for new natural alternatives. The plant species Syagrus cocoides Martius, native to Brazil, has shown antihypertensive potential, but its diuretic activity had not yet been explored. The aim of this study was to carry out the bioprospecting of S. cocoides through the evaluation of the phytochemical and pharmacological profiles of the hydroalcoholic extract of its kernels (SYA), with emphasis on diuretic activity in rats. Fruits of S. cocoides were collected in São Luís (MA, Brazil), and the kernels were subjected to drying, grinding, maceration, and extraction with a 70% hydroalcoholic solution to obtain the extract. The chemical characterization of SYA included the determination of total phenols and flavonoids by spectrophotometry, evaluation of antioxidant potential by the DPPH assay, and identification of constituents by GC/MS. For the pharmacological assays, healthy male Wistar rats (Rattus norvegicus), weighing between 150 200 g, were used. The rats received distilled water (0.01 g/kg, orally) and were individually housed in metabolic cages. After 6 hours, urine was collected and volume measured. Animals that excreted at least 40% of the administered water volume were selected for the study. For the evaluation of the diuretic effect, animals were randomized into four experimental groups (n = 5). In the acute protocol, rats received distilled water (0.01 g/kg), hydrochlorothiazide (0.025 g/kg), or SYA at single doses of 0.1 g/kg and 0.3 g/kg, and were monitored for 24 hours. In the seven-day subchronic protocol, groups received distilled water (0.01 g/kg), furosemide (0.01 g/kg), or SYA (0.1 g/kg and 0.3 g/kg). In both protocols, urinary volume, urinary excretion, diuretic action, and diuretic activity were determined, as well as serum biochemical analyses (glucose, calcium, urea, creatinine, total proteins, albumin, globulin, Na⁺, K⁺, Cl⁻, and osmolarity) and urinary analyses (glucose, calcium, urea, creatinine, and osmolarity). In the acute protocol, latency to the first micturition was additionally evaluated. In the subchronic protocol, water and food intake and body weight evolution were also monitored, along with the determination of urinary flow, pH, density, natriuretic and saluretic activity, carbonic anhydrase inhibitory potential, and the relative weight of target organs (kidneys, heart, lungs, liver, and spleen). SYA showed a high concentration of phenols (266.38 ± 0.01 mg GAE/g), flavonoids (83.50 ± 1.98 mg QE/g), and strong antioxidant potential (91% DPPH inhibition). GC/MS analysis identified 19 compounds, with caprylic acid standing out (37.62%). In the acute test, SYA significantly reduced micturition latency and increased urinary volume and electrolyte excretion, especially Na⁺, K⁺, and Cl⁻, with effects sustained for 24 hours. In the subchronic study, a progressive increase in diuresis was observed from the second day onward, satisfactory natriuresis, and carbonic anhydrase inhibitory potential, along with a slight increase in serum glucose, reduction in K⁺ and blood urea nitrogen, increased urinary creatinine and urinary osmolarity, without evidence of significant toxicity in target organs. SYA demonstrated a rapid and sustained diuretic effect, associated with the presence of bioactive compounds with antioxidant action. The extract showed good tolerability and diuretic efficacy, highlighting its diuretic potential for the management of SAH. Studies involving chronic administration of SYA and investigation of its mechanisms of action will be necessary to further elucidate the diuretic effect observed in this study and to support future stages of clinical evaluation for its regulation and validation. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese Mon, 03 Nov 2025 00:00:00 GMT https://tedebc.ufma.br/jspui/handle/tede/7231 2025-11-03T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/6661 Título: Avaliação da atividade citotóxica, gastroprotetora e anti-inflamatória da emulsão do óleo da semente de Euterpe oleracea Mart. em modelos in vitro e in vivo Autor: MENDES, Renato Juvino de Aragão Primeiro orientador: NASCIMENTO, Maria do Desterro Soares Brandão Abstract: Gastrointestinal diseases are a significant concern for global health, negatively impacting quality of life and requiring new effective treatments. Euterpe oleracea Mart. (açaí) is an Amazonian palm whose fixed seed oil, a little-explored byproduct of the species, contains bioactive fatty acids with pharmacological potential in various diseases. Although E. oleracea is widely studied, there are still gaps in knowledge about its potential in the treatment of gastrointestinal disorders. This work aimed to evaluate the cytotoxic, gastroprotective, and anti-inflammatory activity of the E. oleracea seed oil emulsion (EOR) in in vitro and in vivo experimental models. Material and methods: E. oleracea fruits were collected in the municipality of São Luís, MA. After depulping, the seeds were ground in a knife mill to obtain flour, which was then subjected to oil extraction using the Soxhlet method. The fatty acid profile was identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The emulsion (EOR) was prepared with the extracted oil, surfactant compound Tween 80 (8%), and distilled water. Cytotoxicity was evaluated in murine macrophages (RAW 264.7) using the MTT colorimetric assay with concentrations of 62.5, 125, 250, 500, and 1000 µg/mL. In in vivo assays, the gastroprotective potential was determined using the acidified ethanol gastric ulcer (GU) induction model, and the anti-inflammatory potential was determined using the TNBS-induced ulcerative colitis (UC) model, both in Mus musculus Swiss mice. The EOR emulsion was administered orally at doses of 100, 300, 600, and 1000 mg/kg, and the positive control consisted of the drugs Omeprazole 40 mg/kg and Dexamethasone 4 mg. The analyses performed demonstrated that the açaí seed oil emulsion (EOR), whose lipid profile is dominated by oleic (23.55%), myristic (23.51%), linoleic (21.22%), and palmitic (17.69%) acids, exerts a gastroprotective and anti-inflammatory action in murine models of acute gastric lesion (ethanol/HCl) and colitis (TNBS). In gastric ulcer, EOR 300–600 mg/kg markedly reduced the lesion (ILU 57.6% lower), preserved mucosal architecture, and increased mucus production, with performance comparable to or superior to the positive control. In colitis, a consistent gradient of histological protection was observed, with EOR 300 and 600 mg/kg reaching grade 0 colitis, equivalent to dexamethasone, and accompanied by an increase in GSH and a decrease in MPO levels, indicating less oxidative stress and neutrophilic infiltrate. In parallel, EOR proved to be non-cytotoxic to RAW 264.7 macrophages in the range of 62.5–250 μg/mL (24–48h), supporting a cellular safety profile compatible with biotherapeutic use. Notably, at an intermediate dose (300 mg/kg), a regulatory signal with increased plasma IL-10 was observed, suggesting an additional anti-inflammatory mechanism. The set of findings supports the hypothesis that EOR acts on multiple defense axes in the mucosa—muco-bicarbonate barrier, attenuation of oxidative stress, and containment of neutrophilia—resulting in gastric cytoprotection and resolution of colonic inflammation. In addition to the biomedical impact, the study adds value to an agro-industrial residue, aligning sustainability and innovation. In summary, EOR combines tissue efficacy, mechanistic coherence, and a safety signal, establishing itself as a promising platform for the development of phytotherapeutic/nutraceutical products aimed at gastrointestinal disorders. Future studies should refine dosage and formulation, characterize cytokine kinetics/compartmentalization, and validate mechanisms to advance preclinical translation. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese; Disponibilização parcial do conteúdo a pedido do autor em decorrência de processo de publicação de patente. Fri, 21 Nov 2025 00:00:00 GMT https://tedebc.ufma.br/jspui/handle/tede/6661 2025-11-21T00:00:00Z