Banca de DEFESA: RAFAEL SANTOS DANTAS MIRANDA DÓREA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : RAFAEL SANTOS DANTAS MIRANDA DÓREA
DATA : 06/02/2020
HORA: 09:00
LOCAL: Instituto Multidisciplinar em Saúde
TÍTULO:

EVALUATION OF ANTI-INFLAMMATORY, ANTINOCICEPTIVE AND HEALING ACTIVITY OF THE ETHANOLIC EXTRACT AND SUBFRACTIONS OF THE LEAF OF Schinopsis brasilensis ENGLER

PALAVRAS-CHAVES:

Schinopsis brasiliensis Engler. Antinociceptive. Anti-inflammatory. Braúna.

PÁGINAS: 118
GRANDE ÁREA: Ciências Biológicas
ÁREA: Farmacologia
SUBÁREA: Farmacologia Geral
RESUMO:

Schinopsis brasiliensis Engler, popularly known as “Braúna”, is widely used in folk medicine to treat pain, fever, cough and other diseases. This study aimed to evaluate the antinociceptive, anti-inflammatory and healing activity of S. brasiliensis Engler from Bahia semi-arid, collected in the region of the National Forest Contendas do Sincorá (FLONA), according to ethnopharmacological data of the region. Previous tests carried out with the crude extract (ethanolic) and fractions have already proven the antinociceptive and anti-inflammatory action present in Brauna leaf. Thus, the aim of this study was to evaluate the antinociceptive and anti-inflammatory activity of S. brasiliensis leaf subfractions, to initiate the identification process of bioactive compounds, as well as to elucidate the possible mechanisms of action of these subfractions. The results were obtained through the collection and identification of plant species, phytochemical analysis, ethanolic extract preparation, fractions and subfractions, isolation and identification of compounds. The subfractions tested were hexane (H1, H2, H3, H4) and dichloromethane (D1, D2, D3, D4 and D5). To evaluate antinociceptive and anti-inflammatory activity, tests for abdominal acetic acid-induced writhing, leukocyte recruitment into the peritoneal cavity, evaluation of Evans blue peritoneal extravasation, nociception induced by formalin injection were performed. For chronic inflammation, the granuloma test induced by subcutaneous cotton pellet implantation was used. An experimental excisional wound model was performed to evaluate the healing activity of the leaf extract. For toxicological evaluation, acute toxicity tests were performed in Wistar rats and toxicity against Artemia salina (TAS). Statistical analysis was performed by one-way or two-way ANOVA, parametric approach, followed by Bonferroni's multiple comparison test, with p <0.05. The leaves of S. brasiliensis have polyphenols, tannins, saponins, flavonoids, alkaloids and steroids in both the crude extract and the studied fractions. Gas chromatographic analysis coupled with mass spectrophotometry identified 36 substances in the hexane and dichloromethane fraction, among them Ethyl Galate, a substance of high pharmacological interest. In the acetic acid induced abdominal writhing experiment, subfractions H2, H3, H4 and D1 (50 mg/kg) significantly reduced nociception (p <0.05). The ethanolic extract (100 mg/kg) presented antinociceptive activity with opioid action and inhibitory synthesis of nitric oxide (p <0.05). In the intraplantar formalin injection induced nociception test, subfractions H2, H3, H4, D1, D2, D3, D4 and D5 (50 mg/kg) reduced the number of formalin-induced flinches in phase 1 of the experiment, (p> 0.05) and in phase 2, the subfractions H3, H4, D1, D2, D4 and D5 significantly decreased nociception compared to the vehicle group (p <0.05). None of the subfractions decreased paw edema (p> 0.05). The subfractions D2, D3, D4 and D5 were able to increase the pain threshold of the animals in the Von Frey experiment (p <0.05). The subfractions H2, H3, H4, D1 and D5 (50 mg/kg) showed anti-inflammatory activity reducing the neutrophil migration to the peritoneal cavity (p <0.05), and the possible mechanism of anti-inflammatory action of the H3, H4, D3, D4 and D5 subfractions were due to decreased TNF-a cytokine in treated animals and elevation of IL-10 cytokine when animals were treated with D1 subfraction. There was no decrease in vascular permeability by subfractions evaluated in the Evans blue extravasation test (p> 0.05). Ethanolic extract (50 and 100 mg/kg) and all subfractions tested reduced the weight of granulomatous tissue formed in relation to the control group (p <0.05), similar to the reduction promoted in the dexamethasone group (p> 0.05). The ethanolic extract did not reduce the area of excision wound contraction in rats relative to the vehicle group (p> 0.05). Acute toxicity evaluation revealed changes in hematological, hepatic and renal patterns in animals treated with a single dose of 2000 mg/kg of Braúna ethanolic extract. The cytotoxicity was evaluated against the Artemia saline test and the average dose found was 93 μg/ml, being considered very active. Thus, it can be concluded that S. brasiliensis Engler leaves have relevant therapeutic potential characterized by the presence of compounds with proven activity, as well as having significant antinociceptive and anti-inflammatory activities, and for being safe in the evaluated therapeutic doses. Thus, Brauna leaf is an important natural source for the identification of new molecules and compounds for therapeutic purposes, and can be used by the population in a sustainable way, helping in the environmental protection of the species.

MEMBROS DA BANCA:
Externo ao Programa - 1788171 - BRUNO OLIVEIRA MOREIRA
Externo ao Programa - 3071194 - DAIANA SILVA LOPES
Externo ao Programa - 2342538 - GUILHERME BARRETO CAMPOS
Interno - 1561874 - LUCAS MIRANDA MARQUES
Presidente - 1553274 - REGIANE YATSUDA