Banca de DEFESA: NADJA MARIA DA COSTA MELO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : NADJA MARIA DA COSTA MELO
DATE: 28/09/2021
TIME: 14:00
LOCAL: Videoconferência - Link para acesso: http://meet.google.com/giw-irnf-hye
TITLE:

CHEMICAL CHARACTERIZATION AND CHEMOPREVENTIVE EFFECT OF LYOPHILLED HYDROETHANOLIC EXTRACT FROM Cereus jamacaru P.DC. (MANDACARU) IN EXPERIMENTAL MODEL OF INFLAMMATORY BOWEL DISEASE

KEY WORDS:

Fatty Acids; Chemical analysis; Cactaceae; Colitis; Chemoprevention

PAGES: 152
BIG AREA: Ciências Biológicas
AREA: Farmacologia
SUMMARY:

Inflammatory bowel diseases (IBD) are chronic inflammatory pathologies associated with genetic alterations and environmental factors. The drugs available for treatment can cause potentially serious adverse effects, showing the need to search for new therapeutic strategies. Foods rich in bioactive compounds with anti-inflammatory activity stand out, such as Cereus jamacaru P. DC. This research aimed to chemically characterize and evaluate the anti-inflammatory effect of the Lyophilized Hydroethanolic Extract of Cereus jamacaru P.DC. in an experimental model of inflammatory bowel disease induced by 2,4-dinitrobenzene sulfonic acid (DNBS). The mandacaru cladodes were collected in the city of Jucurutu/RN, the thorns were removed, cut and dried, then they were ground, going through maceration with ethanol and water, obtaining the Lyophilized Hydroethanolic Extract of Cereus jamacaru (EHCJ). The phytochemical prospection of EHCJ was carried out by liquid chromatography coupled to a mass spectrometer to assess the presence of phenolic compounds. In the study of the intestinal anti-inflammatory activity were used Rattus norvegicus (Wistar), adult females (n = 8/group), weight 230 ± 20 g, randomly distributed in the groups: normal control, DNBS collitic control, sulfasalazine 250 mg/Kg and EHCJ (50, 100 and 200 mg/kg/day). Intestinal, macroscopic and microscopic clinical parameters, volatile compounds and fatty acids present in feces, inflammatory markers such as myeloperoxidase enzyme (MPO) dosage, gene expression were evaluated mitogen activated protein kinase (MAPK) and metalloproteinase 9 (MMP-9), expression of the kappa beta factor gene and protein (NF-κB p65); cytokine dosages (TNF-α, IL-10 and IL-1β; evaluation of oxidative stress by measuring malondialdehyde (MDA) and reduced glutathione (GSH); integrity of the intestinal barrier through the expression of the occludin gene (OCL) and expression of the mucin 2 (MUC-2) and occlusion zone (ZO-1) proteins. The results of the phytochemical analysis identified the compounds derived from benzoic acid, saccharide, Kampferol-3-O-dirhamnosyl-hexoside, Isorhamnetin-3-O-dirhamnosyl-glucoside, Kaempferol-3-O-rutinoside, Isorhamnetin-3-O-rutinoside and oxo-dihydroxy-octadecenoic acid. The GC-MS of feces identified 18 compounds, which were fatty acids, hydrocarbons, sterols and phenol according to the fragmentation patterns. In the colitis model, pretreatment with EHCJ at doses of 50, 100 and 200 mg/kg was able to cause chemoprevention observed through the Disease Activity Index (IAD) (p < 0.05). Furthermore, it reduced the colonic damage induced by DNBS with a reduction in the macroscopic damage score (p<0.05). The treatment reduced MPO enzyme activity (p<0.05) and colonic MDA levels (p<0.01) and increased GSH levels (p<0.05) for all doses tested. The extract also reduced tissue levels of the cytokines TNF-α (p<0.0001) and IL-1β (p<0.05) and increased IL-10 at a dose of 200 mg/Kg (p<0.01 ). The preventive effect was also demonstrated by the increased expression of the OCL gene, involved in the integrity of the intestinal barrier and decreased expression of the markers of the MAPK (p<0.01) and NF-κB p65 (p<0.0001) pathways. Histopathological analyzes show that EHCJ significantly reduced the infiltrate density (p<0.001) and immunohistochemistry exhibited increased immunoreactivity for MUC-2 (p<0.01) and ZO-1 (p<0.05) and a reduction of this immunostaining for NF-κB proteins p65 (p<0.05) and MMP-9 (p<0.05). Thus, preclinical results indicate that EHCJ is a product rich in bioactive compounds, beneficial in the chemoprevention of colitis, and may, in the future, become an alternative in the treatment of human IBD.

BANKING MEMBERS:
Presidente - 2330188 - GERLANE COELHO BERNARDO GUERRA
Interna - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Externo à Instituição - RENAN OLIVEIRA SILVA DAMASCENO - UFPE