Xianglian Zhixie Tablet Antagonizes Dextran Sulfate Sodium-Induced Ulcerative Colitis by Attenuating Systemic Inflammation and Modulating Gut Microbiota

Yilin Li; Tingting Wang; Beibei Ma; Shangyue Yu; Hailuan Pei; Shiqiu Tian; Yingying Tian; Chuang Liu; Xinyue Zhao; Zeping Zuo; Zhibin Wang

doi:10.2147/JIR.S423240

Xianglian Zhixie Tablet Antagonizes Dextran Sulfate Sodium-Induced Ulcerative Colitis by Attenuating Systemic Inflammation and Modulating Gut Microbiota

J Inflamm Res. 2023 Sep 28:16:4331-4346. doi: 10.2147/JIR.S423240. eCollection 2023.

Authors

Yilin Li^#¹, Tingting Wang^#², Beibei Ma², Shangyue Yu¹, Hailuan Pei¹, Shiqiu Tian¹, Yingying Tian¹, Chuang Liu¹, Xinyue Zhao¹, Zeping Zuo², Zhibin Wang^{1

2}

Affiliations

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
² Beijing Tongrentang Technology Co., LTD. Pharmaceutical Factory, Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Xianglian Zhixie Tablet (XLZXT), a classical traditional Chinese medicine formulation, is commonly used to treat Ulcerative Colitis (UC) in China. However, the therapeutic mechanisms of XLZXT for UC have yet to be fully understood. This study aimed to investigate the curative benefits of XLZXT and its associated mechanisms for healing UC in mice.

Methods: In the present study, the 1% dextran sulfate sodium (DSS) solution was used to establish the UC model in C57BL/6N mice. To investigate the therapeutic effects of XLZXT on DSS-induced UC mice, several parameters were measured, including DAI score, colon length, spleen index, pathological changes in colon tissue, and levels of inflammatory factors in plasma and colon tissue. By investigating the gut microbiota, assessing the levels of intestinal mucosal protein expression, and looking at the proteins involved in the TLR4/MyD88/NF-B p65 signaling pathway, the mechanisms of XLZXT impact on UC were investigated. Mouse feces were examined for patterns of gut microbiota expression using high-throughput sequencing of 16S rRNA.

Results: XLZXT effectively alleviated UC symptoms and colon pathological damage in DSS-induced UC mice. It improved body weight loss, stool consistency, and hematochezia, while also repairing colon damage. Moreover, it down-regulated pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), and up-regulated anti-inflammatory cytokines (such as IL-10). XLZXT also increased the expression of MUC-2, Occludin and ZO-1, while decreasing the expression of NF-κB, MyD88 and TLR4. Additionally, it regulated gut microbiota disorder by increasing the abundance of beneficial bacteria and reducing the adhesion of intestinal harmful bacteria.

Conclusion: XLZXT demonstrated therapeutic effects on DSS-induced UC mice. The mechanisms may be associated with repairing the intestinal mucosal barrier, regulating the TLR4/MyD88/NF-κB p65 signaling pathway, and restoring the balance of gut microbiota.

Keywords: TCM; TLR4/MyD88/NF-кB p65 signaling pathway; gut microbiota; ulcerative colitis.

Grants and funding

This work was supported by National key research and development program (2019YFC1711400).