Rosa canina methanol extract can restore endoplasmic reticulum homeostasis and protein trafficking and sorting in a dextran sulfate sodium‐induced inflammatory bowel disease phenotype in Caco‐2 cells

Abstract

Inflammatory bowel disease (IBD) is one of the most common gastrointestinal disorders with accelerating incidence, hence the need to search for novel therapeutic approaches. Rosa canina L. is a well-known medicinal plant that exhibits several biological activities. Recent in vivo studies have demonstrated the antioxidant and anti-inflammatory effects of Rosa canina methanol extract (RCME) in a dextran sulfate sodium (DSS)-induced IBD-like phenotype. In the current study, we investigated the potential effect of RCME on restoring disrupted endoplasmic reticulum (ER) homeostasis and protein trafficking alterations in DSS-treated Caco-2 cells. Our results showed that RCME significantly inhibited the DSS-induced increase in the expression of ER stress markers, including activation transcription factor 4 (ATF4), immunoglobulin-binding protein (BiP), C/EBP homologous protein (CHOP), ERAD-enhancing a-mannosidase-like proteins (EDEM), glucose regulated protein 94 (Grp94) and X-box binding protein (XBP1). Moreover, upon RCME treatment, the impaired trafficking and polarized sorting of intestinal sucrase-isomaltase (SI) and dipeptidyl peptidase-4 (DPPIV) was significantly restored. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. These findings indicate that RCME exhibits promising effects in IBD by acting on the ER level and further on the membrane integrity by enhancing the sorting of membrane associated proteins.