Avaliação de toxicidade e da atividade anti-inflamatória intestinal do extrato aquoso das folhas de Ipomoea asarifolia (Desc.) Roem. & Schult

Abstract

Ipomoea asarifolia (Desc.) Roem. & Schult., Popularly known as “salsa” or “salsa brava”, belongs to the family Convolvulaceae. Previous studies with the extract of I. asarifolia and its major compounds, chlorogenic acid, caffeic acid and rutin, have shown excellent antiinflammatory activity. Thus, the objective of this work was to evaluate possible toxic effects of the aqueous extract of the leaves of I. asarifolia (IA), by means of acute and subchronic toxicity tests, as well as to evaluate the preventive effect of the extract in the 2,4- dinitrobenzene sulfonic acid (DNBS)-induced intestinal inflammation. In acute and subchronic toxicity tests, single dose (2000 mg/kg) and serial doses were performed for 28 days (50, 100 and 200 mg/kg) of IA, respectively; in the acute colitis assay, rats pretreated with extract IA (25, 50 and 100 mg/kg) or sulfasalazine 250 mg/kg received intracolonic instillation of DNBS in 50% (v/v) ethanol to evaluate the preventive effect of IA. The hematological, hepatic, renal and central nervous system assessment in toxicity tests did not reveal toxic effects. Whereas in the colitis model, IA showed a protective effect against intestinal inflammation induced by DNBS, with improvement in the disease activity index, in macroscopic intestinal damage and in the colonic weight/length ratio. Pretreatment with the extract promoted downregulation of important molecules involved in intestinal inflammation signaling pathways such as JNK1, NF-κB-p65 and STAT3, while SOCS1 had upregulation. Consequently, IA promoted downregulation of IL-17 and iNOS and reduced levels of IL-1β and TNF-α, pro-inflammatory markers. On the other hand, it significantly increased IL-10, an important anti-inflammatory cytokine. The anti-inflammatory effect of IA was also confirmed by the reduction in colonic MPO activity. In association with these results, there was a significant improvement in oxidative stress with reduced MDA and increased GSH, results that can be attributed to the rich content of phenols and total flavonoids in the extract. Additionally, the IA effect was confirmed in the histological evaluation, demonstrating preservation of the colonic cytoarchitecture, which corroborates with the data referring to upregulation for MUC2, a glycoprotein involved in the integrity of the intestinal barrier. In view of the results presented, conclude that the extract of I. asarifolia has low toxicity and protective activity against intestinal inflammation, revealing the potential for possible adjuvant application in the control of human IBD.