Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA/ROCK signaling pathway.

Yifan Wang,Shuangjiao Deng,Xingxing Liu,Zhexing Shou,Ting Yu,Yujin Liu,Man Zhang,Heng Fan,Qing Tang,Hui Wu,Qianyun Chen,Meng Xu

doi:10.1042/bsr20182297

Yifan Wang, Shuangjiao Deng + Show 10 more

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https://doi.org/10.1042/bsr20182297

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Journal: Bioscience reports	Publication Date: Jul 19, 2019
Citations: 39	License type: CC BY 4.0

Affiliation: Wuhan Union Hospital

Abstract

Oxymatrine (OMT) is an important quinoxaline alkaloid that has a wide range of pharmacological effects and has been shown to alleviate ulcerative colitis due to its profound anti-inflammatory effects. The RhoA/ROCK (Rho kinase) signaling pathway has been shown to be related to the pathogenesis of several autoimmune diseases; however, the specific mechanisms of RhoA/ROCK signaling in inflammatory bowel disease (IBD) remain elusive. Therefore, we sought to determine whether OMT could ameliorate acute intestinal inflammation by targeting the RhoA/ROCK signaling pathway. The potential therapeutic effect of OMT on acute intestinal inflammation and its impact on the RhoA/ROCK signaling pathway were assessed in six groups of mice treated with low, medium and high doses of OMT (25, 50 and 100 mg/kg, respectively), and an inhibitor of ROCK, Y-27632, as a positive control, after initiating dextran sodium sulfate (DSS)-induced acute intestinal inflammation. The model group and normal group were injected intraperitoneally with equal doses of PBS. Our results showed that OMT treatment could protect the integrity of the epithelial barrier, relieve oxidative stress, inhibit the expression of inflammatory mediators and pro-inflammatory cytokines, restrain the differentiation of Th17 cells and promote the differentiation of Treg cells via inhibition of the RhoA/ROCK pathway, thus providing therapeutic benefits for ulcerative colitis (UC). Therefore, inhibiting the RhoA/ROCK pathway might be a new approach that can be used in UC therapy, which deserves to be investigated further.

Highlights

Inflammatory bowel disease (IBD) is a class of chronic intestinal diseases that primarily includes ulcerative colitis (UC) and Crohn’s disease (CD) [1]
After 7 days of treatment, severe intestinal inflammation was present in the dextran sodium sulfate (DSS) group, as evidenced by significant weight loss, colonic shortening and increased disease activity index (DAI) and histologic scores; OMT treatment at doses of 100, 50 and 25 mg/kg and Y-27632 (10 mg/kg) limited body weight loss, diarrhea, bloody stools and colon length shortening
The present study demonstrated that OMT could exert its potential therapeutic effects on DSS-induced acute intestinal inflammation in the following aspects: alleviating symptoms, protecting the integrity of the epithelial barrier, suppressing inflammation, relieving oxidative stress and maintaining the balance between Th17 and Treg cells

Summary

Introduction

Inflammatory bowel disease (IBD) is a class of chronic intestinal diseases that primarily includes ulcerative colitis (UC) and Crohn’s disease (CD) [1]. The etiology and pathology of IBD remain elusive, several factors have been found to play pivotal roles in both the development and incidence of IBD, including genetic factors, immune dysfunction, nitrosative and oxidative stress, intestinal epithelial barrier (IEB) dysfunction and environmental factors [2,3]. Available treatments are effective and beneficial for limiting disease progression. Current treatment methods include immunosuppressive drugs, amino salicylates and glucocorticoids, which are mainly used to treat IBD [5,6,7]. The side effects of these treatments have limited their use [7,8]. In addition to conventional treatment, there is an urgent need to use herbal medicines as alternative and adjuvant treatments [9,10]

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