Syringin protects against colitis by ameliorating inflammation

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory condition with high incidence. Syringin exhibits multiple pharmacological properties, including anti-inflammatory effects. However, the effect of syringin on inflammation of IBD is still unclear. Here, the dextran sulfate sodium (DSS)-induced colitis model was established in vivo. Rat intestinal epithelium IEC6 cells were treated with lipopolysaccharide (LPS) in vitro. Syringin inhibited DSS or LPS-induced overproduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and proinflammatory substances (iNOS, COX-2). Moreover, syringin inactivated the proinflammatory NF-κB p65 pathway by decreasing IκBα phosphorylation at Ser 32. The activation of antioxidant Nrf2 signaling pathway was promoted by syringin. Additionally, LPS-induced inflammation in IEC6 cells was also suppressed by NF-κB inhibitor PDTC and Nrf2 activator RTA408. The anti-inflammatory effects of syringin were comparable to these two reagents. Taken together, our results suggest that syringin shows protective effects on intestinal inflammation through inhibiting NF-κB, while activating Nrf2 signaling pathway in colitis.

Introduction

Inflammatory bowel disease (IBD) is a chronic inflammatory condition, which includes ulcerative colitis (UC) and Crohn's disease (CD) [1,2]. The incidence and prevalence of IBD are stable in northern Europe and USA, whereas it is gradually increasing in southern Europe and Asia [3]. Accumulating evidence has proved that IBD is caused by a variety of factors, such as immune deficiencies, environmental factors and genetic factors [4]. To date, various options, including hormonal, radiation, chemotherapy and surgery, are applied into the IBD treatment [5]. In addition, aminosalicylates, corticosteroids, mycophenolatemofetile and tacrolimus are also used for prevention and treatment of IBD [3]. Although these medicals improved the life quality of patients with IBD in some extent, they were not effective at every stage of the disease. Therefore, to further develop effective therapeutic strategies for IBD, new medicines need to be explored.

Syringin (4-(3-hydroxyprop-1-enyl)-2, 6-dimethoxyphenyl-a-glucopyranoside), which is also defined as eleutheroside B, is extracted from Eleutherococcus senticosus (Araliaceae) [6,7]. It has been documented that syringin shows multiple pharmacological properties. Syringin is applied into treatment of psychogenic behavior disorders, and shows antioxidant as well as immunomodulatory effects [[8], [9], [10]]. However, the role of syringin in IBD is still not reported. Interestingly, previous studies revealed that syringin could downregulate inflammatory cytokine expression in some diseases [11,12]. We hypothesize that syringin might mediate the anti-inflammatory activity on IBD.

Nuclear factor kappa B (NF-κB) is a central regulator of proinflammation in the pathogenesis of IBD and may be involved in the development of ulcerations [13]. For example, Chen et al. discovered that demethyleneberberine, by suppression of NF-κB signaling pathway, reduced inflammatory responses and ameliorated IBD in mice [14]. Rashidian et al. confirmed that inhibition of the toll like receptor 4 (TLR4)/NF-κB signaling pathway played an anti-inflammatory role in 2, 4, 6-trinitrobenzene sulfonic acid-induced rat colitis [15]. Ji et al. revealed that hydroxyproline alleviated dextran sulfate sodium (DSS)-induced colitis via reducing phosphorylation of NF-κB in mice [16]. Interestingly, it has been testified that syringin remarkably downregulated NF-κB expression and showed protective effect on lipopolysaccharide (LPS)-induced acute lung injury in mice [17]. These findings indicate that syringin might improve the inflammation in IBD by regulation of NF-κB signaling pathway. Thus, the current study aimed to investigate the mechanism of syringin involved in protecting against IBD through NF-κB signaling pathway.

In this study, the DSS-induced mice were treated with syringin in vivo. Additionally, the rat intestinal epithelium cell line, IEC6, was used to explore the role of syringin in LPS-induced inflammation in vitro. Taken together, we explored the potential mechanism of syringin in IBD treatment in vivo and in vitro. These data underscore the importance of syringin in improving the patients with IBD.