RESUMO
Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal anti-inflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1ß, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Physalis , Ribes , Ratos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Ésteres/metabolismo , Sacarose/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Citocinas/metabolismo , Colo/patologia , Doenças Inflamatórias Intestinais/patologia , Ácido Trinitrobenzenossulfônico/toxicidadeRESUMO
Inflammatory bowel diseases are characterized by a chronic clinical course of relapse and remission associated with self-destructive inflammation of the gastrointestinal tract. Active extracts from plants have emerged as natural potential candidates for its treatment. Abarema cochliacarpos (Gomes) Barneby & Grimes, Fabaceae (Barbatimão), is a native medicinal plant in to Brazil. Previously we have demonstrated in an acute colitis model a marked protective effect of a butanolic extract, so we decided to assess its anti-inflammatory effect in a chronic ulcerative colitis model induced by trinitrobenzensulfonic acid (TNBS). Abarema cochliacarpos (150 mg/day, v.o.) was administered for fourteen consecutive days. This treatment decreased significantly macroscopic damage as compared with TNBS. Histological analysis showed that the extract improved the microscopic structure. Myeloperoxidase activity (MPO) was significantly decreased. Study of cytokines showed that TNF-α was diminished and IL-10 level was increased after Abarema cochliacarpos treatment. In order to elucidate inflammatory mechanisms, expression of cyclooxygenase (COX)-2 and nitric oxide synthase (iNOS) were studied showing a significant downregulation. In addition, there was reduction in the JNK and p-38 activation. Finally, IκB degradation was blocked by Abarema cochliacarpos treatment being consistent with an up-regulation of the NF-kappaB-binding activity. These results reinforce the anti-inflammatory effects described previously suggesting that Abarema cochliacarpos could provide a source for the search for new anti-inflammatory compounds useful in ulcerative colitis treatment.