Qingjie Fuzheng Granule attenuates 5-fluorouracil-induced intestinal mucosal damage

Abstract

Objective: 5-Fluorouracil (5-FU)-based chemotherapy often causes several drawbacks including weight loss, diarrhea, myelosuppression, and the intestinal mucositis. This study aimed to evaluate the protective effect of Qingjie Fuzheng Granule (QFG) on 5-FU-induced intestinal mucositis in CT-26 tumor-bearing xenograft mice and investigated the possible molecular mechanism.

Methods: Tumor xenograft models of CT-26 cells were generated in BALB/c nude mice, the mice were randomly divided into 4 groups including control, QFG, 5-FU and 5-FU combined QFG groups. The body weight, volume of tumor and diarrhea score of each group were recorded daily. On the fifth day, the blood of mice was collected, the mice were subsequently euthanized and their thymus, spleen, intestine and tumor were removed for the following analysis.

Results: QFG alleviated severe diarrhea and reversed the decrease in the number of white blood cell including granulocyte and lymphocyte induced by 5-FU. QFG could also significantly improve 5-FU-induced several intestinal mucosal damages, and characterized by integrity villus and crypts, the reduction of necrotic cells. QFG decreased the serum levels of TNF-α, IL-1β, and IL-6 and increased the levels of IL-10. Furthermore, QFG inhibited the cellular apoptosis in the jejunum tissue caused by 5-FU via the increasing Bcl-2 expression and decreasing Bax expression. In addition, QFG promoted the cell proliferation via elevating the expression of Cyclin D1 and CDK4 and reducing p21 expression. Meanwhile, QFG could not further impact on the cell apoptosis and proliferation of tumors caused by 5-FU.

Conclusion: QFG attenuated the intestinal mucositis and diarrhea induced by 5-FU via preventive effect on inflammation and its improvement of the intestinal barrier function, inhibiting cell apoptosis and promoting cell proliferation, and without affecting the 5-FU treatment efficiency. The results suggest that QFG may act as a potential agent against chemotherapy-induced intestinal mucositis.

Keywords: 5-fluorouracil; Apoptosis; Inflammation; Intestinal mucosal damage; Proliferation; Qingjie Fuzheng Granule.