International Immunopharmacology 90 (2021) 107194 Available online 4 December 2020 1567-5769/© 2020 Elsevier B.V. All rights reserved. Improvement of magnesium isoglycyrrhizinate on DSS-induced acute and chronic colitis Jian Cui a, 1 , Yan Li a, 1 , Chenyang Jiao a , Jianhua Gao a , Yingxue He a , Beibei Nie a , Lingdong Kong a , Wenjie Guo a, * , Qiang Xu a, b, * a State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China b Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China A R T I C L E INFO Keywords: Colitis Colonic fbrosis Infammation cytokines Gut barrier function Magnesium isoglycyrrhizinate ABSTRACT Infammatory bowel disease (IBD) is a worldwide prototypical complex disease, owing to its multifactorial causes, relapsing and remitting condition and high incidence. Thus, effective therapeutic approaches need to be developed for patients with IBD. Currently, we reported the improving effect of magnesium isoglycyrrhizinate on colitis induced by dextran sulfate sodium (DSS). We found that magnesium isoglycyrrhizinate treatment signifcantly alleviated DSS-induced acute and chronic colitis by inhibiting the infammatory response charac- terized by reduce of the infltrations of immune cell and the level of pro-infammatory cytokines. Besides, magnesium isoglycyrrhizinate treatment signifcantly inhibited the level of ROS and decreased the gut barrier destruction after DSS treatment. Furthermore, the results also showed that administration of magnesium iso- glycyrrhizinate signifcantly reduced the colonic fbrosis. Taken together, these results revealed the potency of magnesium isoglycyrrhizinate on the intestinal infammation, by which points to the possible use of magnesium isoglycyrrhizinate for IBD therapy in clinical applications. 1. Introduction Infammatory bowel disease (IBD) is a complex disorder of the gastrointestinal tract, encompassing ulcerative colitis and Crohn’s dis- ease, mainly characterized by chronic, relapsing pathogenic infamma- tion with a high prevalence worldwide [1–4]. IBD is a progressive and destructive disease, resulted in various complications including frequent bloody stools, abscesses, tissue fbrosis and colorectal cancer [5–7]. Many therapeutics have been developed for IBD such as immunosup- pressive and biologic agents, cytokines inhibitors, modulators of cyto- kine signaling events [8–11]. However, many challenges such as no response to the clinically approved drugs, loss response over time and unacceptable adverse events, remains to be solved. Therefore, there are a large unmet and urgent need to develop new therapeutic approaches. Magnesium isoglycyrrhizinate, is the magnesium derivative of gly- cyrrhizic acid, which has anti-infammatory, antioxidant and hep- atoprotective pharmacological activities [12–16]. Magnesium isoglycyrrhizinate has been clinically used for the treatment of hepatic diseases, including hepatitis, liver fbrosis [17,18]. Additionally, it has been reported that magnesium isoglycyrrhizinate can improve lung injury [19]. Despite the previous work done to elucidate the anti-infammation activity of magnesium isoglycyrrhizinate, whether it can ameliorate colitis remains unknown. Our results showed that magnesium iso- glycyrrhizinate had a signifcant inhibitory effect on DSS-induced acute colitis and chronic colitis by decreasing infammation, maintaining gut barrier as well as inhibiting fbrosis. In summary, we ascertain the ef- fcacy of magnesium isoglycyrrhizinate in treating colonic infammation for the frst time and these fndings will be crucial for the development of therapeutic strategies targeting colonic infammation. 2. Materials and methods 2.1. Mice C57BL/6 mice (female, 6–8 weeks, 20–24 g) were purchased from Jiangsu Gempharmatech co., ltd (Nanjing, China). Mice were main- tained in an animal facility under standard laboratory conditions for 1 * Corresponding authors at: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. E-mail addresses: guowj@nju.edu.cn (W. Guo), molpharm@163.com (Q. Xu). 1 These authors contributed equally to this work. Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp https://doi.org/10.1016/j.intimp.2020.107194 Received 17 September 2020; Received in revised form 6 November 2020; Accepted 8 November 2020