Improvement of magnesium isoglycyrrhizinate on DSS-induced acute and chronic colitis

doi:10.1016/j.intimp.2020.107194

International Immunopharmacology

Volume 90, January 2021, 107194

https://doi.org/10.1016/j.intimp.2020.107194 Get rights and content

Highlights

•
The effect of magnesium isoglycyrrhizinate on DSS-induced colitis was examined for the first time.
•
Inflammation was significantly inhibited by Magnesium isoglycyrrhizinate.
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Colonic epithelial damage as well as fibrosis was significantly improved by Magnesium isoglycyrrhizinate.

Abstract

Inflammatory 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 significantly alleviated DSS-induced acute and chronic colitis by inhibiting the inflammatory response characterized by reduce of the infiltrations of immune cell and the level of pro-inflammatory cytokines. Besides, magnesium isoglycyrrhizinate treatment significantly inhibited the level of ROS and decreased the gut barrier destruction after DSS treatment. Furthermore, the results also showed that administration of magnesium isoglycyrrhizinate significantly reduced the colonic fibrosis. Taken together, these results revealed the potency of magnesium isoglycyrrhizinate on the intestinal inflammation, by which points to the possible use of magnesium isoglycyrrhizinate for IBD therapy in clinical applications.

Introduction

Inflammatory bowel disease (IBD) is a complex disorder of the gastrointestinal tract, encompassing ulcerative colitis and Crohn’s disease, mainly characterized by chronic, relapsing pathogenic inflammation with a high prevalence worldwide [1], [2], [3], [4]. IBD is a progressive and destructive disease, resulted in various complications including frequent bloody stools, abscesses, tissue fibrosis and colorectal cancer [5], [6], [7]. Many therapeutics have been developed for IBD such as immunosuppressive and biologic agents, cytokines inhibitors, modulators of cytokine signaling events [8], [9], [10], [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 glycyrrhizic acid, which has anti‐inflammatory, antioxidant and hepatoprotective pharmacological activities [12], [13], [14], [15], [16]. Magnesium isoglycyrrhizinate has been clinically used for the treatment of hepatic diseases, including hepatitis, liver fibrosis [17], [18]. Additionally, it has been reported that magnesium isoglycyrrhizinate can improve lung injury [19].

Despite the previous work done to elucidate the anti-inflammation activity of magnesium isoglycyrrhizinate, whether it can ameliorate colitis remains unknown. Our results showed that magnesium isoglycyrrhizinate had a significant inhibitory effect on DSS-induced acute colitis and chronic colitis by decreasing inflammation, maintaining gut barrier as well as inhibiting fibrosis. In summary, we ascertain the efficacy of magnesium isoglycyrrhizinate in treating colonic inflammation for the first time and these findings will be crucial for the development of therapeutic strategies targeting colonic inflammation.

Section snippets

Mice

C57BL/6 mice (female, 6–8 weeks, 20–24 g) were purchased from Jiangsu Gempharmatech co., ltd (Nanjing, China). Mice were maintained in an animal facility under standard laboratory conditions for 1 week prior to experiments and provided water and standard chow. Animal welfare and experimental procedures were carried out in accordance with the Guide for the Care and Use of Laboratory Animals (Ministry of Science and Technology of China, 2006) and the related ethical regulations of Nanjing

Magnesium isoglycyrrhizinate ameliorated experimental colitis induced by DSS in mice

To investigate the improvement of magnesium isoglycyrrhizinate on intestinal inflammation, acute colitis model induced by DSS was employed (Fig. 1A). Mice were divided into 5 groups (n = 6): control, DSS alone, DSS with magnesium isoglycyrrhizinate (1.25, 2.5, and 5 mg/kg, i.p.). As shown in Fig. 1B–E, compared with control group, mice administrated with 2.5% DSS showed colitis symptoms: significant weight loss, shortened colon length, and elevated disease activity index (DAI). Comparing with

Discussion

IBD, called incurable disease with low mortality, comprising Crohn’s disease and Ulcerative colitis, is a chronic immunologically mediated disease results from genetics, environment and intestinal microbes [3], [4]. In the current study, we determined magnesium isoglycyrrhizinate had an obviously improving effect on colitis in the mouse model. According to previous studies, magnesium isoglycyrrhizinate has been characterized the role of in ant‐inflammatory, antioxidant and hepatoprotective

CRediT authorship contribution statement

Jian Cui: Data curation, Investigation, Writing - original draft. Yan Li: Investigation. Chenyang Jiao: Investigation. Jianhua Gao: Investigation. Yingxue He: Investigation. Beibei Nie: Investigation. Lingdong Kong: Supervision, Validation. Wenjie Guo: Conceptualization, Funding acquisition, Supervision, Writing - review & editing. Qiang Xu: Project administration, Funding acquisition, Writing - review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 81730100, 81922067), Fundamental Research Funds for the Central Universities (020814380114), National Training Program for Innovation and Entrepreneurship for Undergraduate Students (202010284052X), Young Scholar Foundation from Cyrus Tang Foundation.

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¹: These authors contributed equally to this work.

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Improvement of magnesium isoglycyrrhizinate on DSS-induced acute and chronic colitis

Highlights

Abstract

Introduction

Section snippets

Mice

Magnesium isoglycyrrhizinate ameliorated experimental colitis induced by DSS in mice

Discussion

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgments

Lancet

Bioorg. Med. Chem.

Biomed. Pharmacother.

Int. Immunopharmacol.

Biomed. Pharmacother.

Int. Immunopharmacol.

Immunity

Cell

Gastroenterology

Inflammatory bowel disease

N. Engl. J. Med.

Epidemiology and risk factors for IBD

Nat. Rev. Gastroenterol. Hepatol.

The global burden of IBD: from 2015 to 2025

Nat. Rev. Gastroenterol. Hepatol.

Ulcerative colitis

Lancet

Extraintestinal manifestations and complications in IBD

Nat. Rev. Gastroenterol. Hepatol.

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

Nature

Current and emerging therapeutic targets for IBD

Nat. Rev. Gastro Hepat.

Evolving therapeutic goals in ulcerative colitis: towards disease clearance

Nat. Rev. Gastroenterol. Hepatol.

Biologic agents for IBD: practical insights

Nat. Rev. Gastroenterol. Hepatol.

IL-12, IL-23 and IL-17 in IBD: immunobiology and therapeutic targeting

Nat. Rev. Gastroenterol. Hepatol.

Magnesium isoglycyrrhizinate has hepatoprotective effects in an oxaliplatin-induced model of liver injury

Int. J. Mol. Med.

Magnesium isoglycyrrhizinate ameliorates doxorubicin-induced acute cardiac and hepatic toxicity via anti-oxidant and anti-apoptotic mechanisms in mice

Exp. Ther. Med.

Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug-induced liver injury: A phase II trial

Liver Int.

Magnesium isoglycyrrhizinate prevents the nonalcoholic hepatic steatosis via regulating energy homeostasis

J. Cell Mol. Med.