Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway.

Xiao-Min Zhang,Jin-Ying Ou,Ling-Hui Nie,Shan-Shan Chen,Ling-Ling Zhu,Xiao Hu,Lei Gao

doi:10.1155/2020/8653783

Abstract

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

Highlights

Radiotherapy is one of the effective methods for the treatment of malignant abdominal and pelvic tumors [1, 2]
Since GL exhibited markedly antiinflammatory effects in radiation enteritis (Figure 3), we further evaluated the effects of GL on High-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4) pathway by western blotting analysis and immunofluorescence analysis, which is known to play a crucial role in various inflammatory diseases. e elevation of HMGB1 and TLR4 expression was detected in the model group (Figure 5)
It has been reported that GL could alleviate inflammatory responses and was adopted as a therapeutic agent in a variety of inflammatory diseases, for instance cerebral ischemia/reperfusion-induced inflammation and arthritis [33]. erefore, in our present study, we evaluated the potential anti-inflammatory effects of GL on radiation enteritis

Summary

Introduction

Radiotherapy is one of the effective methods for the treatment of malignant abdominal and pelvic tumors [1, 2]. ROS and NOS are immediately generated [5,6,7], which can cause severe cell damage, including DNA damage and the release of intracellular cytokines [8, 9]. Radiation-induced DNA damage can act as a damage-associated molecular pattern (DAMP) to stimulate inflammatory responses, as well as destruction of the intestinal epithelial barrier mediated by abdominal radiation. As an early mediator of inflammation, HMGB1 is implicated in a variety of inflammatory diseases, including sepsis [15], arthritis and pneumonia [16, 17], thereby indicating that HMGB1 maybe be a promising therapeutic target for inflammatory diseases [18]

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