Potential of Peruviose A and B from Physalis peruviana L calyces to treat Inflammatory Bowel Disease: In vivo and in vitro studies

Abstract

Phytotherapy constitutes an emerging alternative strategy for the treatment of inflammatory bowel disease (IBD). Although medicinal plants are integral part of Colombian culture, very few of them have been studied deeply.1 One example is Physalis peruviana (Cape gooseberry), which has demonstrated anti-inflammatory activity.2 In this work, we investigated the therapeutic potential of Peruviose A and B; two new sucrose esters recently isolated by us from calyces of P. peruviana, using TNBS-colitis model. For this, ten rats were assigned to groups: control, untreated TNBS-colitis, and treated with a mixture of Peruviose A and B (5 and 10 mg/kg, i.p.) for two weeks. Inflammation was evaluated measuring macroscopic/histologic damage, MPO activity, and cytokine levels. In vitro studies were performed using LPS-stimulated peritoneal macrophages treated with compounds (0.01 – 10 µg/mL). Complementarily, we assessed their effect on E. coli growth. Treatment with Peruviose A/B, at both doses, did not show hepatic or renal injury, while reduced significantly the extent and severity of tissue damage, and colonic weight/length ratio by 58%. In agreement, microscopic disturbances were diminished with reduction of inflammatory cells, distortion of crypts architecture, and necrosis. Compounds also reduced MPO activity (71%), TNF-α (33%) and IL-1β (64%) levels, while IFN-γ and IL-6 were not modified. In vitro assays showed a dose-response inhibition of NO and PGE2 liberation (IC50= 3.9 and 0.07 µg/mL, respectively). Additionally, compounds did not affect E. coli growth, suggesting that the activity is not related with effects on commensal bacteria. Our results provide the first evidence that Peruviose A/B can effectively ameliorate experimental IBD, giving a new application to calyces of P. peruviana, which constitutes a waste in fruit production and an unexplored source of bioactive molecules.