Therapeutic Potential of the Combination of Pentoxifylline and Vitamin-E in Inflammatory Bowel Disease: Inhibition of Intestinal Fibrosis

Abstract

Background: Although intestinal fibrosis is a consequence of recurrent inflammation in Inflammatory bowel disease (IBD), alleviating inflammation alone does not prevent the progression of fibrosis, suggesting that the development of direct anti-fibrotic agents is necessary. This study aimed to evaluate the anti-fibrotic properties of combination treatment with pentoxifylline (PTX) and vitamin E (Vit-E) on human primary intestinal myofibroblasts (HIMFs) and the therapeutic potential of the combination therapy in murine models of IBD. Methods: HIMFs were pretreated with PTX, Vit-E, or both, and incubated with TGF-β1. We performed Western blot, qPCR, collagen staining, and immunofluorescence to estimate the anti-fibrotic effects of PTX and Vit-E. The cytotoxicity of these was investigated through MTT assay. To induce murine models of IBD for in vivo study, C57BL/6 mice were treated with repeated cycles of dextran sulfate sodium (DSS), developing chronic colitis. We examined whether the combined PTX and Vit-E treatment would effectively ameliorate colonic fibrosis in vivo. Results: We found that the co-treatment with PTX and Vit-E suppressed TGF-β1-induced expression of fibrogenic markers, with decreased expression of pERK, pSmad2, and pJNK, more than either treatment alone in HIMFs. Neither PTX nor Vit-E showed any significant cytotoxicity in given concentrations. Consistently with the in vitro results, the co-administration with PTX and Vit-E effectively attenuated colonic fibrosis with recovery from thickening and shortening of colon in murine models of IBD. Conclusions: These findings demonstrated that the combination of PTX and Vit-E exhibits significant anti-fibrotic effects in both HIMFs and in vivo IBD models, providing a promising therapy for IBD.

A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis

“…Long-term therapy with PTX and vitamin E together was shown to decelerate the advancement of intestinal fibrosis, preserving gut resilience and potentially improving the quality of life for individuals with IBD. The results also suggest that vitamin E supplementation may contribute to maintaining intestinal flexibility in IBD patients [398].…”

Fish Oil Ameliorates Vibrio parahaemolyticus Infection in Mice by Restoring Colonic Microbiota, Metabolic Profiles, and Immune Homeostasis

“…The colon tissues were stained with the intestinal fibrosis markers type I (TICP) and type III (TIIICP) collagen protein, and the extent of cellular apoptosis in the colonic mucosal was determined by TUNEL staining based on immunofluorescence analysis . The DAPI was applied to label nuclei to count the total cells.…”

The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease

“…Overall, these findings suggest that vitamin E plays a significant role in preserving intestinal epithelial barrier integrity by upregulating TJ protein expression and maintaining the mucus layer, thereby contributing to the overall function and health of the gut. Interestingly, vitamin E supplementation effectively alleviates colonic fibrosis by inhibiting the expression of TGF-β1-induced fibrosis markers, p-ERK, p-Smad2, and p-JNK, and hinders colonic thickening and shortening in DSS-caused IBD models [ 59 , 60 ].…”