Abstract
Salvianolic acid B (Sal B) is isolated from the traditional Chinese medical herb Salvia miltiorrhiza and is reported to have a wide range of therapeutic benefits. The aim of this study was to investigate the effects of Sal B on epithelial barrier dysfunction in rat colitis and to uncover related mechanisms. Rat colitis model was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The intestinal barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in vitro respectively. The protein expression related to intestinal barrier function was studied using western blotting. The effects of Sal B on inflammatory responses, oxidative damage and colitis recurrence were also studied in this study. The intestinal barrier dysfunction in colitis was reversed by Sal B, accompanied with the decrease of tight junction proteins, and the effect could be blocked by microRNA-1(miR-1) inhibition. The inflammatory responses, oxidative damage and colitis recurrence were also decreased by Sal B. The colitis symptoms and recurrences were ameliorated by Sal B, and restoration of impaired barrier function via downregulation of MLCK by miR-1 maybe involved in this effect. This study provides some novel insights into both of the pathological mechanisms and treatment alternatives of inflammatory bowel disease.
Highlights
Inflammatory bowel disease (IBD) is complex multi-factorial inflammatory diseases, of which Crohn’s disease (CD) and ulcerative colitis (UC) are the two most common forms (Garcia de Tena et al, 2002)
The effects of Salvianolic acid B (Sal B) on oxidative stress and epithelial barrier function in normal rats were respectively studied before the analysis of Sal B induced modulation on those in colitis rats
ELISA results showed that the low dose and high dose of Sal B did not affect the expression of NADPH oxidase 4 (NOX4), inducible nitric oxide synthase (iNOS), MDA, GSH, and SOD (Figures 2A–E) from colon tissue, while the high dose of Sal B decreased the expression of long myosin light chain kinase (MLCK) (Figure 2F) from colon tissue
Summary
Inflammatory bowel disease (IBD) is complex multi-factorial inflammatory diseases, of which Crohn’s disease (CD) and ulcerative colitis (UC) are the two most common forms (Garcia de Tena et al, 2002). Role of free radicals and epithelial barrier functions has attracted much attention in the pathogenesis of IBD recently (Almenier et al, 2012). Infiltration of inflammatory cells into the mucosa and release of free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species, could lead to Salvianolic Acid B Alleviated Colitis inflammatory cascade (Almenier et al, 2012; Nagib et al, 2013). Tissue damage and additional recruitment of inflammatory cells could be caused by these free radicals, which sustain the inflammatory cascade (Keshavarzian et al, 2003; Reuter et al, 2010; Almenier et al, 2012)
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