Improvement of magnesium isoglycyrrhizinate on DSS-induced acute and chronic colitis
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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2022, Food ChemistryCitation Excerpt :In addition, studies using DSS-induced colitis models have reported that activation of MD2 and MyD88 is associated with stimulation of the NF-κB signaling pathway and production of pro-inflammatory cytokines (Sumneang, Apaijai, Chattipakorn, & Chattipakorn, 2021; Wang et al., 2019). Additionally, the formation and maintenance of the epithelial tight junction complex is an important component of the intestinal barrier (Cui et al., 2021, Zeisel, Dhawan, & Baumert, 2019). Here, we demonstrated that inducing colitis in mice with DSS, the expressions of connexins such as ZO-1, occludin, and Claudin-1 were downregulated.
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2021, Toxicology and Applied PharmacologyCitation Excerpt :H&E staining and immunohistochemical analysis were performed on paraffin-embedded colonic tissue sections as described previously. Histological evaluation of H&E-stained colonic sections was graded in a blinded manner (Cui et al., 2021): 0, no signs of inflammation; 1, low leukocyte infiltration; 2, moderate leukocyte infiltration; 3, high leukocyte infiltration, moderate fibrosis, high vascular density, thickening of the colon wall, moderate goblet cell loss, and focal loss of crypts; and 4, transmural infiltrations, massive loss of goblet cell, extensive fibrosis, and diffuse loss of crypts. The quantification of immunohistochemistry was performed using Plugins called IHC Profiler (https://sourceforge.net/projects/ihcprofiler).
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These authors contributed equally to this work.