DSpace Coleção: PPGPN

Avaliação dos efeitos dos liofilizados dos extratos hidroalcóolicos da casca do fruto e da folha de Spondias tuberosa Arruda em modelo de senescência induzida por radiação UVA em células de queratinócitos humanos imortalizados (HaCaT)

2026-02-26T00:00:00Z

Título: Avaliação dos efeitos dos liofilizados dos extratos hidroalcóolicos da casca do fruto e da folha de Spondias tuberosa Arruda em modelo de senescência induzida por radiação UVA em células de queratinócitos humanos imortalizados (HaCaT) Autor(es): Gomes, Myllena Lustosa Cabral Orientador: Medeiros, Isac Almeida de Abstract: UVA radiation, predominant in sunlight, induces photoaging through oxidative stress, DNA damage, and activation of inflammatory pathways. In this scenario, natural products rich in antioxidant metabolites, such as Spondias tuberosa Arruda, show potential for modulating cellular senescence, although they still require further scientific investigation. This study aimed to evaluate the effects of lyophilized hydroalcoholic extracts of the fruit peel (LEHCST) and leaf (LEHFST) of Spondias tuberosa Arruda (umbu tree) in a UVA radiation-induced senescence model using immortalized human keratinocyte cell culture (HaCaT). Preliminary chemical characterization assays were performed using nuclear magnetic resonance (NMR), allowing the structural identification of secondary metabolites. Initially, a model of UVA radiation-induced cellular senescence was standardized in HaCaT cells exposed to UVA radiation (6, 13, and 19 J/cm²) for 20, 40, and 60 minutes, respectively, using viability assays, senescence assays, superoxide anion production assays, and morphological analyses with evaluations immediately, 24, and 48 hours post-radiation. The 40-minute exposure, evaluated 24 and 48 hours after radiation, was defined as the most suitable model, as it induced a significant increase in oxidative stress and senescence without causing excessive cellular damage. The cultivated HaCaT were divided into two groups: Basal (CTL: without radiation and treated only with LEHCST or LEHFST extracts at concentrations of 0.01, 0.05, 0.1, 0.5, and 1.0 μg/mL) and UVA (CTL, UVA 40’, and the groups exposed to UVA radiation and treated with LEHCST or LEHFST extracts at concentrations of 0.01, 0.05, 0.1, 0.5, and 1.0 μg/mL) for 24 and 48 hours for evaluation of the assays mentioned above. NMR analysis revealed signals compatible with phenolic compounds and other aromatic structures. The LEHCST and LEHFST extracts did not alter viability, senescence, or superoxide anion production in the basal group. In the UVA-induced model, both extracts significantly reduced the production of superoxide anions and the percentage of senescent cells when compared to CTL (p<0.05). The results indicate that the extracts exhibit anti-senescent activity in HaCaT cells exposed to UVA radiation, possibly associated with their antioxidant action. The novelty of these findings is noteworthy, reinforcing the potential of the extracts in preventing cutaneous photoaging. Keywords: U Editor: Universidade Federal da Paraíba Tipo: Dissertação

O monoterpeno hidroxicitronelal como potencial agente antiepiléptico e neuroprotetor : um estudo in sílico e in vivo

2025-06-26T00:00:00Z

Título: O monoterpeno hidroxicitronelal como potencial agente antiepiléptico e neuroprotetor : um estudo in sílico e in vivo Autor(es): Pires, Hugo Fernandes Oliveira Orientador: Salvadori, Mirian Graciela da Silva Stiebbe Abstract: Epilepsy is a chronic brain disorder that affects approximately 70 million people worldwide and is characterized by recurrent and spontaneous epileptic seizures. Current treatment focuses on reducing the frequency and intensity of seizures but does not provide a cure. Furthermore, due to the toxicity and high rate of refractoriness to the available medications, there is an urgent need for new drugs that are both effective and possess better safety profiles. In the literature, monoterpenes already show preliminary evidence of antiepileptic activity. Thus, the aim of this work is to evaluate the antiepileptic and neuroprotective effects of hydroxycitronellal through in silico and in vivo methodologies. To this end, molecular docking studies were conducted to assess its potential chemical interaction with key targets involved in epilepsy. Additionally, the compound’s acute oral toxicity and its LD50 were evaluated using OECD protocol no. 423 in male Swiss albino mice (25–30 g). Subsequently, to assess the possible antiepileptic and neuroprotective effects of the compound, the rodents were subjected to an acute seizure model induced by pentylenetetrazole and to the chemical kindling model. As for the results, the in silico study showed that hydroxycitronellal may interact with important pharmacological targets related to epilepsy, such as the GABAA receptor, the channels NMDA, Nav 1.6 and Cav 1.2, and the SV2A protein. The in vivo study demonstrated that the compound is not toxic when administered acutely and orally and that it exhibits antiepileptic and neuroprotective effects at doses of 200, 100, 50, 25, and 12.5 mg.kg-1. Among these, the 100 mg.kg-1 dose was identified as the most effective under the experimental conditions evaluated, while the 6.25 mg.kg-1 dose was determined as the threshold for loss of antiepileptic effect. Furthermore, the compound was able to increase the levels of reduced glutathione in the hippocampus of the animals. In the kindling model, the compound delayed epileptogenesis, increasing the latency to the first seizure and to death. Histological analysis revealed neuronal protection and a reduction in glial nodules compared to the control group. Therefore, based on this study, hydroxycitronellal emerges as a promising antiepileptic drug candidate; however, further studies are necessary to elucidate its potential pharmacological mechanism of action. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Múltiplas abordagens usando espectrometria de massas, estudos de desreplicação, e métodos quimiométricos suportadas no desenvolvimento de estratégias para distinção, agrupamento e descoberta de compostos bioativos de espécies de Solanum subg. Leptostemonum (Solanaceae)

2025-02-24T00:00:00Z

Título: Múltiplas abordagens usando espectrometria de massas, estudos de desreplicação, e métodos quimiométricos suportadas no desenvolvimento de estratégias para distinção, agrupamento e descoberta de compostos bioativos de espécies de Solanum subg. Leptostemonum (Solanaceae) Autor(es): Silva, Anauara Lima e Orientador: Tavares, Josean Fechine Abstract: Morphological and phylogenetic studies have not been sufficient to clarify the relationships between Solanum species and define limits between subordinate groups, such as the clades of the subgenus Leptostemonum. Thus, there is a need to use new approaches, such as the analysis of secondary metabolites, based on modern analytical methodologies and techniques, which can provide support to elucidate relationships and define interspecific and infrageneric limits, especially in relation to Brazilian species. Despite Brazil being recognized as one of the centers of diversity and endemism of the subgenus, information about its diversity is little known, with the occurrence of endemic species that have never been studied or included in morphological, phylogenetic and chemosystematic treatments already carried out. Many of them also have their chemical composition and biological potential completely unexplored. In the present study, several approaches are established, supported by the development of methodologies and strategies for screening and identification of metabolites (dereplication) of dried herbarium specimens, extract and fractions of the fresh plant, based on chemical profile studies by HPLC-MS and aided by statistical methods. In addition to using HPLC-MS data for the guided isolation of new compounds with bioactive potential. Thus, this work is divided into 4 chapters: In chapter one, metabolites from the aerial parts of Solanum jabrense Agra and Nee were analyzed, with the aid of molecular networks, with the aim of proving the hypothesis that studies using HPLC-MS and herbarium specimens are capable of determining the chemical profile of the species and identifying the presence of metabolites that can be used as distinctive metabolites and/or chemosystematic markers. This plant was chosen as a model due to its endemism and availability of material in our laboratory, in addition to being little explored regarding its bioactive potential. The second chapter describes the development and implementation of the HPLC-MS-based methodology for the analysis of the chemical profile of 72 herbarium specimens of Solanum subgenus Leptostemonum, verifying whether this approach, together with statistical methods, can be useful to distinguish and classify the species used, assisting in the chemotaxonomy of the subgenus Leptostemonum, comparing the groupings obtained in the statistical analyses to the existing taxonomic classifications. In chapter three, the plant material of S. jabrense was collected and the same extraction methodology was reproduced, on a proportional scale, carried out for the herbarium specimens to prepare the crude hydroalcoholic extract. The crude extract and the alkaloid-rich fraction obtained by precipitation of the crude extract were analyzed by HPLC-MS to determine the chemical content and compare it with herbarium specimens, and tested for larvicidal and repellent activity against Aedes aegypti. In chapter four, three chemical molecules with bioactive potential were isolated from the hydroalcoholic extract of S. jabrense, one new and two previously known. This is the first report of the three structures for the species. These isolated substances will later be used as seeds in dereplication studies. Editor: Universidade Federal da Paraíba Tipo: Tese

Avaliação do possível efeito ansiolítico-símile do composto (Z)-N’-(1-benzil-2-oxoindolin-3-ilideno)-2-fluor-benzodrazida por meio de estudos in silico, in vivo e in vitro

2026-02-27T00:00:00Z

Título: Avaliação do possível efeito ansiolítico-símile do composto (Z)-N’-(1-benzil-2-oxoindolin-3-ilideno)-2-fluor-benzodrazida por meio de estudos in silico, in vivo e in vitro Autor(es): Gurgel, Luiz Henrique Sampaio Orientador: Felipe, Cícero Francisco Bezerra Abstract: Anxiety disorders constitute a relevant public health problem, characterized by high prevalence and important therapeutic limitations, which justifies the prospecting of new pharmacological alternatives. The present study aimed to evaluate the possible anxiolytic-like effect of the compound (Z)-N’-(1-benzyl-2-oxoindolin-3-ylidene)-2-fluorobenzhydrazide (ISA) through in silico, in vivo, and in vitro approaches. In silico analyses indicated that the compound presents stable interactions with serotonergic receptors 5-HT1A, 5-HT2A, and 5-HT3A. In the in vivo studies, ISA promoted an anxiolytic-like effect in the Elevated Plus Maze, evidenced by an increase in the number of entries and the time spent in the open arms; this effect was partially reversed in the presence of flumazenil, an antagonist of GABAA receptors. In the Open Field and Rota Rod tests, the compound did not alter locomotor activity and motor coordination of the animals, respectively. In the experimental model of anxiety induced by pentylenetetrazol (PTZ), pretreatment with the compound was able to prevent anxiety-like behavior in the tested animals. Finally, the in vitro assays demonstrated that the compound was able to increase hippocampal GSH concentration in mice subjected to the experimental model of anxiety induction, in addition to showing low toxicity in glial cell culture. Taken together, the results suggest that the compound may interact satisfactorily with serotonergic receptors involved in the neurobiology of anxiety disorders. Furthermore, ISA showed an anxiolytic-like effect that appears to involve, at least in part, the GABAA receptor, without causing impairments in locomotor activity or motor coordination, at the doses and administration routes used. Finally, ISA showed an antioxidant effect related to increased GSH production in hippocampal homogenates and low toxicity in glial cell culture. Editor: Universidade Federal da Paraíba Tipo: Dissertação