TITULO DO PROJETO DE PESQUISA QUE SERA APRESENTADO NO EXAME:
Avaliacao da Atividade do Extrato Livre e Nanoparticulado das Folhas de Commiphora leptophloeos (Mart.) J.B. Gillet em Modelos de Inflamacao Intestinal e Cancer Colorretal Quimicamente Induzidos ___________________________________________________________________
TITULO DO PROJETO DE TESE:
Efeito do extrato das folhas de Commiphora leptophloeos livre e nanoparticulado em modelo de cancer colorretal associado a colite (CAC) em camundongos alimentados com dieta rica em gordura _________________________________________________________________________
TITULO DO ARTIGO SUBMETIDO:
Chemopreventive and immunomodulatory effects of phenolic-rich extract of Commiphora leptophloeos against inflammatory bowel disease: Preclinical evidence
Inflammatory Bowel Disease; Colorectal cancer; Imburana; Burseraceae; Commiphora leptophloeos;
Commiphora leptophloeos (Mart.) J.B. Gillet, from the Burseraceae family, is a plant native to Brazil, found in the Caatinga, Cerrado, and Amazon biomes. It is popularly known as imburana for its medicinal properties in treating inflammation in general. However, reports show its effect in combating gastrointestinal symptoms such as colic and diarrhea. It has important secondary metabolites, such as the flavonoids orientin, vitexin, and quercetin, which have recognized intestinal anti-inflammatory activity. Thus, this study aimed to evaluate the effect of the free and nanoparticulate hydroethanolic extract of the leaves of C. leptophloeos in models of intestinal inflammation (preventive and curative) and colorectal cancer associated with colitis and to evaluate the phytochemical profile of the extract. In the intestinal inflammation model induced by the 2,4-dinitrobenzene sulfonic acid (DNBS) - preventive model, the extract (doses of 300, 400, and 500mg/kg p.o.) was able to negatively regulate important signaling pathways in intestinal inflammation such as NF-κB and COX-2, reducing inflammatory cytokines and oxidative stress markers, compared to the DNBS group (p<0.05). In the colitis model induced by dextran sulfate sodium (DSS) - curative model, both the free extract (dose of 400 mg/kg v.o.) and the nanoparticulate system (480 µg/mL v.o.) obtained significant results (p<0.05) in the regulation of markers involved in the initiation of the intestinal inflammatory cascade such as TLR2/4, JNK1/2 and COX-2 and consequently in the regulation of inflammatory chemokines and cytokines, compared to the DSS control. In both models, an improvement in clinical symptoms and intestinal cytoarchitecture was observed. Furthermore, the free extract and nanoparticulate system showed antitumor activity, acting on important signaling pathways of carcinogenesis, regulating Tpr53, Ctnnb1, Bax, and Bcl-2, in the reduction of the colonoscopic index and tumor volume, as well as improvement in clinical symptoms and colonic cytoarchitecture. In conclusion, C. leptophloeos exerts both preventive and curative intestinal anti-inflammatory activity in vivo models, in addition to antitumor activity, making it possible to propose the development of a new phytoingredient for the treatment of chronic inflammatory diseases.