Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice

Abstract

Background Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. Methods Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence. Results Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% ( P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% ( P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group. Conclusions These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Salvia miltiorrhiza Bge. (Danshen) for Inflammatory Bowel Disease: Clinical Evidence and Network Pharmacology-Based Strategy for Developing Supplementary Medical Application

“…SAB, the major water-soluble compound of Danshen with anti-inflammatory and anti-oxidative properties, might attenuate abnormality of MLCK after TNBS exposure in rats. Similar to the results in vivo , SAB induced microRNA-1 to suppress MLCK detected by dual luciferase reporter assay in IL-1β-stimulated Caco2 intestinal monolayer, consequently ameliorating loss of epithelial ZO-1 and claudin-2 ( Xiong et al, 2016 ; Feng et al, 2020 ). Similarly, Salvianolic acid A (SAA) attenuated disruption of ZO-1 and Occludin mRNA triggered by DSS ( Wang et al, 2018 ).…”

“…A feature of IBD is irreversibly degraded integrity of the intestinal epithelial barrier, including TJs classified into Zonula occludens (ZO), Occludins, and claudins ( Lee, 2015 ). Myosin light chain kinase (MLCK), which monitors permeability of the epithelial barrier, interacts with TJs by contraction of the perijunctional actomyosin ring ( Feng et al, 2020 ). Therefore, research has focused on the roles of MLCK in colonic epithelium dysfunction.…”

Thiopurines: Recent Topics and Their Role in the Treatment of Inflammatory Bowel Diseases

“…However, the design of the largescale OCTAVE trial did not allow tofacitinib to be used in combination with thiopurines; hence, the safety of two-agent therapy has yet to be verified. Additionally, the use of thiopurines in combination with tofacitinib has not been recommended due to the risk of infection, particularly viral infection, associated with tofacitinib itself, and concerns that two-agent therapy may induce excessive immunosuppression that could break down the intestinal barrier, thereby making it difficult to control disease activity (Sandborn et al, 2017;Xiong et al, 2019;Feng et al, 2020). Clear evidence is currently lacking on the clinical significance of long-term combination use of biological agents and thiopurines.…”

Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments

“…Mice in group III, IV, and V were administered SASP or naringin by gavage once a day for seven successive days. Mice in groups II–V were given drinking water containing DSS (4% w/v) dissolved in autoclaved distilled water, to induce colitis symptoms ( Feng et al, 2020 ). Control group I mice were given autoclaved distilled water and otherwise, treated in the same way.…”