Abstract

Salvianolic acid A (SAA) is an active phenolic acid derived from Salvia miltiorrhiza Bunge (Danshen). To explore whether SAA has a therapeutic effect against inflammatory bowel disease (IBD), an acute colitis model was induced in rats by administering 3% dextran sodium sulphate (DSS) for one week. SAA in doses of 4 and 8 mg/kg/day was given by tail vein injection during DSS administration. Both dosages of SAA ameliorated the colitis symptoms, with decreases observed in the disease activity index. A high dosage of SAA (8 mg/kg/day) promoted a longer colon length and an improved colonic tissue structure, compared with the DSS-treated rats not receiving SAA. SAA dose-dependently decreased colonic gene expression of pro-inflammatory cytokines (IL-1β, MCP-1 and IL-6). Moreover, a high dosage of SAA protected against DSS-induced damage to tight junctions (TJ) in the rats’ colons, by increasing TJ-related gene expression (ZO-1 and occuldin). Finally, using 16S rRNA phylogenetic sequencing, we found that SAA modulated gut microbiota imbalance during colitis by increasing the gut microbial diversity as well as selectively promoting some probiotic populations, including Akkermansia spp. Our study suggests that SAA is a promising candidate for the treatment of IBD.

Highlights

  • Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a group of chronic disorders characterized by inflammation in the gastrointestinal tract [1].The typical phenomena of UC occur in the inner lining of the rectum or the large intestine, causing frequent diarrhea, abdominal cramps, and rectal bleeding in some cases

  • The Disease Activity Index (DAI) and colon length were measured, and histological examinations of the distal colon of the rats were performed to assess the protective effect of Salvianolic acid A (SAA)

  • The histological examination of the distal colon of the rats showed serious microscopic mucosa inflammation, with typical observations including crypt damage, infiltration, ulceration, and edema in the intestinal epithelial layer in the dextran sodium sulphate (DSS) group, while SAA high-dosage group alleviated these pathological changes in the colon (Figure 2C,D)

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Summary

Introduction

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a group of chronic disorders characterized by inflammation in the gastrointestinal tract [1]. Nutrients 2018, 10, 791 salicylic acid, steroid hormones, and 6-mercaptopurine, are the main drug currently used for IBD treatments.and These drugs aim to induce remission andcurrently prevent relapse [3]. These treatments hormones, 6-mercaptopurine, are the main drug used for IBD treatments These drugs are associated with several limitations, including some these side effects, drug and several a high aim to induce remission and prevent relapse [3]. Chinese medicine (TCM), which include plant-based remedies [4]. A series of studies traditional Chinese medicine (TCM), which include plant-based remedies [4]. Salvia miltiorrhiza extract on chemically (azoxymethane and dextran sodium sulfate) colitis in mice was investigated, the and dextran sodium sulfate) induced colitis ininduced mice was investigated, and the researchersand found researchers found that it significantly reduced the disease activity

Animals and Treatments
Histologic Analysis
Microbiota Analysis
Statistical Analyses
Effect of Salvianolic Acid A on DSS-Induced Colitis Symptoms
Effects of SAA on Gut Microbial Composition in DSS-Induced-Colitis Rats
Discussion
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