Programa de Pós-Graduação em Ciências Farmacêuticas
Permanent URI for this communityhttps://repositorio.ufrn.br/handle/123456789/11920
Browse
7 results
Search Results
Master Thesis Obtenção, caracterização físico-química e avaliação biológica in vitro de dispersões sólidas amorfas com a,B-amirenona(Universidade Federal do Rio Grande do Norte, 2024-12-13) Bulhões, Sávio Gorgônio Paes de; Lima, Adley Antonini Neves de; https://orcid.org/0000-0002-3798-3915; http://lattes.cnpq.br/4061809277935577; http://lattes.cnpq.br/3969304016037186; Duarte, Fernanda Ílary Costa; https://orcid.org/0000-0003-2052-9334; http://lattes.cnpq.br/3035470083983748; Rocha, Hugo Alexandre de Oliveira; https://orcid.org/0000-0003-2252-1221; http://lattes.cnpq.br/4651814546820796Obesity is a global public health issue, associated with diets high in fats and carbohydrates, as well as sedentary lifestyles, affecting approximately 25% of the Brazilian population, especially women. Lifestyle changes are the conventional treatment but face adherence challenges, leading to an increased search for medications and surgeries, which come with adverse effects. Triterpenes, such as α,βamirenone (ABAME), have shown antiobesity potential, but their poor water solubility limits their oral effectiveness. To overcome this limitation, solid dispersions (SD) of ABAME were prepared with the polymers PEG and PVP using malaxation (MX) and physical mixing (MF) techniques, aiming to improve solubility and pharmacological properties. The samples were characterized by techniques such as Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TG), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM), indicating that the interaction between ABAME and the polymers promoted a transition from the crystalline to the amorphous state, as well as greater thermal stability compared to the isolated compound, particularly in the SDs obtained by MX. The quantification of ABAME was performed by High-Performance Liquid Chromatography (HPLC), meeting ANVISA standards and demonstrating success in SD development. In in vitro biological tests, the SDs showed greater efficacy in lipase inhibition compared to isolated ABAME, especially those prepared by MX, with a reduced IC50. Although antioxidant tests showed moderate results, with lower performance in total antioxidant capacity (TAC) and DPPH radical scavenging assessments, the SDs demonstrated excellent reducing power. The data, though preliminary, highlight the antiobesity potential of the SDs, marking them as a promising strategy compared to conventional treatments, which often present adverse effects.Master Thesis Caracterização físico-química, citotoxicidade e propriedades bioativas do óleo da castanha de sapucaia (Lecythis pisonis)(Universidade Federal do Rio Grande do Norte, 2025-03-31) Santos, Júlia da Costa; Sousa Júnior, Francisco Canindé de; Assis, Cristiane Fernandes de; https://orcid.org/0000-0003-2042-4348; http://lattes.cnpq.br/3721560802857426; http://lattes.cnpq.br/6489481856774447; Matsui, Katia Nicolau; Oliveira Júnior, Sérgio Dantas deLecythis pisonis, popularly known as sapucaia, is a plant species widely distributed in Brazil. Its seeds, leaves and stem are traditionally used to treat diabetes, coughs, muscle pain and itching, among other conditions. The aim of this study was to evaluate the physicochemical characteristics, cytotoxicity, and bioactive properties of sapucaia nut oil. The oil was characterized using the proton nuclear magnetic resonance and gas chromatography coupled with mass spectrometry, revealing a high content of unsaturated fatty acids, especially linoleic (53%) and oleic (25%) acids. Additionally, the characterization included Fourier transform infrared spectroscopy (FTIR) and the evaluation of physical-chemical parameters such as moisture, acidity, peroxide, saponification, iodine and density, all of which confirmed the presence of unsaturated fatty acid chains and attested to the quality of the oil. Moreover, thermogravimetric analysis (TG/DTA) indicated high thermal stability, with decomposition starting at 288 °C. No cytotoxic activity was found in CHO-K1 (Chinese hamster ovary) and HepG2 (human hepatocarcinoma) cells. The oil had a total phenolic concentration (TPC) of 291.77 µg EAG.g-1 and showed antioxidant activity against ABTS radicals (2,2'- azinobis 3-ethylbenzothiazoline-6-sulfonic acid) of 4.28 µmol TE.g-1 and DPPH (2,2- diphenyl-1-picrylhydrazyl) of 14.84 mMol TE.g-1. The total antioxidant capacity (CAT) of the methanolic fraction of the oil was 20.51 mg AA.g-1. Sapucaia nut oil also demonstrated in vitro inhibitory capacity against the enzymes involved in carbohydrate digestion - α-amylase (94.01%), α-glucosidase (98.03%) and amyloglucosidase (84.88%) – and exhibited antifungal activity against Candida albicans with a minimum inhibitory concentration of 10 mg/mL. The results of this study contribute to a better understanding of the physicochemical characteristics, biological activities, and potential applications of sapucaia oil, aiming to disseminate knowledge and encourage interest in the food, pharmaceutical and cosmetics industries. Futhermore, the study seeks to enhance the value of the production chain, boost the local economy, and promote the preservation of the species, thereby generating income opportunities for the producing regions.Master Thesis Obtenção de nanoemulsão contendo extrato da espécie vegetal Jatropha gossypiifolia e avaliação da atividade antidermonecrótica frente a peçonha de Bothrops erythromelas(Universidade Federal do Rio Grande do Norte, 2024-03-18) Batista, Beatriz Ketlyn da Cunha; Pedrosa, Matheus de Freitas Fernandes; http://lattes.cnpq.br/2929963416385218; http://lattes.cnpq.br/9241484075605588; Silva, Ângelo Roncalli Alves e; Santos, Jacinthia Beatriz Xavier dos; Lima, Maira Conceição Jerônimo de SouzaSnakebite is a Neglected Tropical Disease of category A, which affects around 2.7 million people per year worldwide. In Brazil, the genus Bothrops has the greatest clinical relevance, with the species Bothrops erythromelas standing out in the Northeast region. Tissue necrosis is one of the most relevant local damages caused by this genus, given the possibility of loss of function of the bitten limb and even amputation, impacting the victim's quality of life. The ineffectiveness of antivenom in combating local damage caused by envenomation encourages the search for new complementary therapies, especially medicinal plants. The species Jatropha gossypiifolia (Jg) is used in popular culture for inflammation, wounds and snakebites. Therefore, this study aimed to develop a topical nanoemulsion containing the hydroethanolic extract of Jg leaves, to evaluate the healing and antidermonecrotic activity. The phytochemical characterization of the Jg extract was performed using High Performance Liquid Chromatography coupled to a photodiode array detector (HPLC-DAD), which detected the presence of the flavonoids vitexin, luteolin derivates and apigenin derivatives, and quantification of the phenolic content and flavonoids, with 95.08 ± 5.46 mg of gallic acid/g of extract and 137.92 ± 0.99 mg of quercetin/g of extract, respectively. Next, a nanoemulsion containing Jg extract (NJg) was developed and physicochemical characterization was performed, in which NJg (n=2) presented an average size of 164.96 ± 9.487 nm, PDI of 0.217 ± 0.026, pH of 5.89 ± 0.0281 and phenolic content of 32.039 ± 14.628 mg of gallic acid/g of extract, showing no color variation or phase separation. Over the course of 4 weeks, the characteristics were maintained. To evaluate in vitro cytotoxicity, the hemolytic and crystal violet assay was performed, in which the extract and NJg did not show toxicity at the concentrations tested (32.25-250 μg/mL) for human erythrocytes and murine fibroblasts (NHI/3T3). Furthermore, the antioxidant activity of the extract and NJg was performed, reaching an IC50 of 0.2999 and 0.4646 μg/μL for the ABTS∙+ radical, respectively, and of 0.2899 and 0.4374 μg/μL for the radical DPPH, respectively. Next, the skin irritation of the NJg was evaluated, demonstrating the absence of irritation. In the evaluation of healing activity in vivo, NJg presented significant wound closure from the 5th day of treatment, when compared to the no treatment group, being 45% for NJg and 21% for the no treatment group, and on the 8th day reaching 58%. Besides, NJg promoted the reduction of nitrite, myeloperoxidase activity and cytokines. An evaluation of the in vitro inhibition of phospholipase A2 (PLA2) and hyaluronidase from Bothrops erythromelas venom (BeV) was also carried out, with maximum inhibition of 23% (1:100; BeV:NJg) and 24% (1:0.25; BeV:NJg), respectively. Finally, the in vivo inhibition of the dermonecrotic halo caused by Pbe was evaluated, demonstrating that NJg was able to reduce the formation of this halo from 24h after induction. Therefore, it can be suggested the participation of the extract's compounds in the pharmacological action, especially the flavonoids, which mainly have antioxidant and anti-inflammatory actions. In conclusion, the results suggest that the developed NJg is promising and may be contributing to the treatment of local damage from snakebite.Master Thesis Desenvolvimento de formulações cosméticas contendo o extrato de Prosopis juliflora e avaliação das atividades antioxidante e antitirosinase(Universidade Federal do Rio Grande do Norte, 2023-11-24) Silva, Tássyo Leandro da; Ferrari, Márcio; Damasceno, Gabriel Azevedo de Brito; https://orcid.org/0000-0002-2425-7586; http://lattes.cnpq.br/5782539548696465; http://lattes.cnpq.br/3819354181697704; Amaral, Juliano Geraldo; Barreto, Stella Maria Andrade Gomes; https://orcid.org/0000-0001-7830-626X; http://lattes.cnpq.br/2234955265649411The rich biodiversity of plant species in Brazil enables studies for the development of products containing natural compounds. Prosopis juliflora, popularly known as mesquite, is a plant brought from Peru, widespread in the Brazilian Caatinga where it has become an invasive species. Studies report antimicrobial, antioxidant, antimalarial, and antitumor actions among others. Such activities are related to the presence of secondary metabolites such as alkaloids, terpenoids, tannins and flavonoids, present in different parts of this plant. Some of these metabolites can be used by the cosmetic industry as active ingredients for application in different activities. Therefore, this work aimed to evaluate the antioxidant and antityrosinase activity of P. juliflora fruit extract and develop cosmetic formulations containing this extract with the aim of harmonizing skin color. To this end, the extract obtained using previously standardized methodologies was evaluated for the concentration of phenolic compounds (0.21 ± 0.01 mg EAG/g) and total flavonoids (1.71 ± 0.26 µg EQ/mg). Furthermore, the extract under study was characterized using LC-MS-TOF. The in vitro safety of the extract was evaluated using cellular cytotoxicity tests and the samples did not show cytotoxic effects. The in vitro antioxidant activity was evaluated using different methodologies and demonstrated the ability to block the oxidation cascade in the initiation and propagation phases. The antityrosinase action was evaluated using enzymatic methodology and the extract showed an inhibition activity of 62.48 ± 2.09 at a concentration of 30.00 mg/mL. Formulations with Disodium EDTA, Phenoxyethanol (and) Ethylhexyl Glycerin, Distilled Water, Sodium Acrylates Copolymer Lecithin, Polyacrylamide (and) C13-14 Isoparaffin (and) Laureth-7 and 3.00% of the studied plant extract were subjected to preliminary and accelerated stability tests. The formulations were stable in accelerated stability tests after a period of 60 days. This research, in addition to contributing scientifically by demonstrating the use of a Caatinga plant in antioxidant cosmetic products and for homogenizing skin color, will also contribute to adding value to the P. juliflora production chain, giving value to aspects of Brazilian environmental, social and biodiversity responsibilities.Doctoral Thesis Uso do resíduo industrial do sisal (Agave sisalana Perrine) em produtos cosméticos sustentáveis com atividades antioxidante e fotoprotetora(Universidade Federal do Rio Grande do Norte, 2022-07-22) Daher, Cláudia Cecílio; Ferrari, Márcio; Giordani, Raquel Brandt; http://lattes.cnpq.br/5032750980466610; https://orcid.org/0000-0002-2425-7586; http://lattes.cnpq.br/5782539548696465; http://lattes.cnpq.br/5337129241199109; Assis, Cristiane Fernandes de; Verissimo, Lourena Mafra; Damasceno, Gabriel Azevedo de Brito; Rocha Filho, Pedro Alves daSisal is the main hard fiber produced in the world. In the chemical composition of the Agave sisalana residue, carbohydrates, saponins and phenolic compounds are found, which are used in the cosmetic industry with antioxidant and photoprotective activities. This work aimed to develop a multifunctional formulation with antioxidant and photoprotective activities from the industrial residue of A. sisalana. An ultrasonic extraction of the solid plant material was performed, varying the concentrations of the extracting agent (50% ethanol/water (v/v), 80% ethanol/water (v/v) and 100% ethanol). The extract with the highest yield was chemically characterized and evaluated for in vitro antioxidant activity. Ten photoprotective formulations were prepared varying the component concentrations and the shear time. The A. sisalana extract at a concentration of 1.0% was incorporated into the most stable formulations and their preliminary and accelerated stability was evaluated and the emulsions were investigated for safety. The photoprotective formulations containing or not the extract that were stable after 90 days, had their in vivo Sun Protection Factor, UVA Protection Factor, critical wavelength, and protection against visible and blue light determined. Ultrasound extraction using 50% ethanol/water (EH 50) as extractor vehicle showed the best yield. The extract exhibited a good concentration of phenolic compounds and showed in vitro antioxidant activity at different stages of the oxidative cascade. Emulsions without and with 1.0% A. sisalana extract remained stable for 90 days, presenting a desirable rheological behavior for a cosmetic for topical use: pseudoplastic and thixotropic. The emulsion containing A. sisalana extract proved to be safe after clinical studies. It was verified that the addition of the extract to the photoprotective formulation statistically increased the SPF when compared to the formulation without the extract with protection against UVA radiation, critical wavelength, absorption of visible and blue light and they fit in with the requirements of current legislation for sunscreens. In view of the results presented, the solid residue of A. sisalana can be indicated as a component of photoprotective and antioxidant cosmetic formulations.Master Thesis Estudo fitoquímico e avaliação do efeito gastroprotetor e anti-inflamatório do extrato do cladódio de Nopalea cochenillifera em modelos animais(Universidade Federal do Rio Grande do Norte, 2021-11-22) Silva, Elaine Cristine Souza da; Langassner, Silvana Maria Zucolotto; Guerra, Gerlane Coelho Bernardo; http://lattes.cnpq.br/5677318431530876; https://orcid.org/0000-0002-2768-0793; http://lattes.cnpq.br/7390416147619446; http://lattes.cnpq.br/9551845574128253; Araújo, Daline Fernandes de Souza; Alves, Jovelina Samara FerreiraNopalea cochenillifera, from the Cactaceae family, is popularly known as “sweet” or “miúda” palm and is widely cultivated in the Northeast region of Brazil. This research aimed to characterize the chromatographic profile and evaluate the gastroprotective and anti-inflammatory effect of the hydroethanolic extract of N. cochenillifera. For this, the cactaceae cladode was collected, cut and dried in an oven, crushed, macerated with ethanol and water, obtaining the hydroethanolic extract, which was lyophilized. The phytochemical study of the hydroethanolic extract was performed by Thin Layer Chromatography (TCD) and High Performance Liquid Chromatography Coupled with Mass Spectrometer (HPLC-ESI-IT). The content of total phenols and flavonoids was evaluated by ultraviolet spectrophotometry. TLC evaluation indicated the presence of phenolic compounds, including flavonoids. Analysis by HPLC-ESI-IT identified the presence of six compounds, with a predominance of caffeic acid hexoside. The content of total phenols and flavonoids in the extract was 67.85% and 46.16%, respectively. In the pharmacological study to evaluate the anti-inflammatory activity, Swiss mice were randomly divided into groups (n=.5) carrageenan (treated with saline), dexamethasone (1 mg/g), N. cochenillifera extract (200; 400 or 600 mg/kg). Myeloperoxidase (MPO) enzyme activity was evaluated as a marker of neutrophil infiltration. For the evaluation of the gastroprotective activity, Rattus norvegicus (Wistar) were used, randomly distributed in groups (n=7) control gastric lesions, healthy group (saline), extract of N. cochenillifera (50, 100 and 200 mg/kg) and ranitidine (50 mg/kg), administered by gavage. The results show that the extract has an antiedematogenic activity, the dose of 600 mg/kg showed the percentage of inhibition of edema of 58.00% ± 6.02 (P< 0.01). The anti-inflammatory activity of the extract could be confirmed by the significant reduction of the enzyme myeloperoxidase (MPO) (P< 0.01). In models induced by ethanol and indomethacin, the extract showed that it prevented the formation of gastric lesions, at a dose of 100 mg/kg, ethanol model (P<0.001); and at doses of 100 mg/kg (P<0.05) and 200 mg/kg (P<0.01), in the indomethacin model. Macroscopic evaluation of the stomachs showed a reduction in the ulceration index, accompanied by a reduction in myeloperoxide (MPO) and malondialdehyde (MDA) activity, preservation of GSH, reduction of gastric levels of pro-inflammatory cytokines (TNF-α and IL-1β), and elevation of IL-10. Histopathological analyzes revealed that the extract prevented the morphological changes induced by ethanol and indomethacin, preserving gastric tissue integrity, and also reduced the inflammatory infiltrate, which was confirmed by the reduction of MPO. In the immunohistochemical analysis, the extract decreased the expression of the COX-2 enzyme and increased the expression of SOD at a dose of 200 mg/kg when induced by indomethacin and ethanol. The pre-treatment with extract of N. cochenillifera did not change the pH, volume or total acidity of gastric juice, but preserved mucus secretion and could have a cytoprotective effect. The results of the present work provide preclinical evidence that the N. cochenillifera extract has gastroprotective and anti-inflammatory activities, which may be related to the richness of phenolic compounds, especially flavonoids.Doctoral Thesis Avaliação da atividade quelante, antioxidante, anticoagulante, imunomoduladora e cicatrizante do peptídeo aniônico (TanP) da peçonha do escorpião Tityus stigmurus(Universidade Federal do Rio Grande do Norte, 2021-06-30) Melo, Menilla Maria Alves de; Pedrosa, Matheus de Freitas Fernandes; http://lattes.cnpq.br/2929963416385218; http://lattes.cnpq.br/8674610000531012; Assis, Cristiane Fernandes de; http://lattes.cnpq.br/0034694007210837; Pontes, Daniel de Lima; http://lattes.cnpq.br/1903229358912987; Carvalho, Eneas de; http://lattes.cnpq.br/8416275144930466; Monteiro, Norberto de Kassio Vieira; http://lattes.cnpq.br/8804303821523487Anionic peptides, or acids, of scorpions correspond to the class of peptides without disulfide bonds, rich in aspartic and / or glutamic acid residues in their primary sequence. TanP is a linear anionic peptide, with 50 amino acid residues and net charge -20, which is present in the venom gland of the scorpion Tityus stigmurus, identified by a transcriptomic approach and after confirmed by mass spectroscopy. A previous study indicated that TanP has a chelating potential for Cu2+ ion, in addition to an immunomodular potential. The therapeutic application of chelating molecules is related to cases of acute or chronic intoxication by metals, neurodegenerative diseases, hematological diseases, healing of skin wounds, cardiovascular diseases and cancer. This work evaluated TanP chelating activity in relation to new metals of biological importance (Fe2+, Ca2+ and Zn2+), by UV-visible spectroscopy, computational methods, and fluorescence, as well as expanding the investigation of the biological potential of the peptide, as an antioxidant, hemostatic, immunomodulatory and wound healing molecule, by in vitro assay. TanP (25 µM) was able to form stable complexes with Fe2+ in a ratio of 1: 5 (TanP: Fe2+). The obtained geometries for Zn2+ and Fe2+ complexes present tetrahedral and octahedral shapes, respectively. Theoretical results suggest that TanP can work as a sensor to identify and quantify Fe2+ ions. The fluorescence intensity of TanP (1.12 µM) decreased significantly after the addition of Fe2+, obtaining that the highest ratio 1: 7.4 (TanP: Fe2+) led to the lowest fluorescence intensity. TanP showed a maximum of 3% of hemolytic activity when evaluated at the highest concentration (50 µM). TanP exhibited DPPH radical scavenging above 70% at all concentrations tested (1 to 25 μM), 89.7% iron chelating activity at 25 μM, 96% hydroxyl radical scavenging activity at 73.6 μM. TanP showed significant anticoagulant activity at concentrations of 12.5 µM and 25 µM for the TP and TTPa assays. No fibrinogenolytic effect was observed. TanP (12.5 and 25 µM) induced release of TNF-α by murine macrophages, in the absence of LPS, this increase being dosedependent. The migration of 3T3 cells was stimulated by TanP (2 µM, 12.5 µM and 50 µM) in an in vitro healing assay. Thus, it is suggesting that the assessment of the chelating potential associated with the antioxidant, anticoagulant, immunomodulatory and healing effects of TanP supports further studies that enable the development of a prototype molecule for therapeutic and biotechnological applications.