RESUMEN
Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. 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. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.
Asunto(s)
Retículo Endoplásmico/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/terapia , Metanol/farmacología , Extractos Vegetales/farmacología , Transporte de Proteínas/efectos de los fármacos , Rosa/química , Animales , Células CACO-2 , Sulfato de Dextran , Dipeptidil Peptidasa 4/metabolismo , Modelos Animales de Enfermedad , Humanos , Enfermedades Inflamatorias del Intestino/inducido químicamente , Mucosa Intestinal/efectos de los fármacos , Microdominios de Membrana/metabolismo , Ratones , Microvellosidades/metabolismo , Fenotipo , Complejo Sacarasa-Isomaltasa/metabolismoRESUMEN
Rosa canina is a well-known medicinal plant used in folk remedy that alleviates various disorders, including inflammation, gastritis, and diarrhea. The objective of this investigation was to identify and quantify the phenolic components of R. canina methanolic extract (RCME) and to determine its protective action with dextran sulfate sodium (DSS)-generated mice colitis model. RCME chemical analysis was done using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry, and experimental animals received RCME at different doses before colitis induction by oral DSS administration during 7 days. Another group received sulfasalazine as a positive control. Colitis damages and RCME benefits were assessed using histopathological and biochemical changes and improvements. Many phenolic compounds have been identified. In addition, the DSS intoxication induced an alteration of colonic epithelium associated with an oxidative stress state. DSS administration led to an increase or decrease of intracellular mediators such as free iron and ionizable calcium. RCME consumption effectively protected against colonic histological/biochemical alterations induced by DSS intoxication providing support for the traditional use of this plant.