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Issue 5, 2018
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Carboxymethyl pachyman (CMP) reduces intestinal mucositis and regulates the intestinal microflora in 5-fluorouracil-treated CT26 tumour-bearing mice

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Abstract

The compound 5-fluorouracil (5-FU) is the first choice chemotherapeutic agent for the treatment of colorectal cancer (CRC), but intestinal mucositis is a primary limiting factor in anticancer therapy. There is currently no broadly effective targeted treatment to cure this side effect. Carboxymethylated pachyman (CMP) is a polysaccharide that is modified from the structure of pachyman isolated from Poria cocos (Chinese name: Fu Ling). Meanwhile, recent studies have shown that CMP exhibits immune regulatory, anti-inflammatory and antioxidant activities. Therefore, the purpose of this study was to evaluate the intestinal protective effect of CMP in 5-FU-treated CT26 tumour-bearing mice and to further explore its underlying mechanism(s) of action. Initially, a CT26 colon carcinoma xenograft mice model was established. The colon length, colon tissue injury, intestinal flora, short-chain fatty acids (SCFAs) and indicators linked to inflammation, antioxidation and apoptosis were then measured. Our results showed that CMP in combination with 5-FU reversed intestinal shortening (p < 0.01) and alleviated 5-FU-induced colon injury (p < 0.001) via suppression of ROS production; increasing the levels of CAT, GSH-Px and GSH; decreasing expression of NF-κB, p-p38 and Bax; and elevating the levels of Nrf2 and Bcl-2. More importantly, CMP had a significant impact and counteracted the intestinal microflora disorders produced by 5-FU by increasing the proportion of Bacteroidetes, lactobacilli, and butyric acid-producing and acetic acid-producing bacteria and restoring the intestinal flora diversity. Overall, this work suggested that CMP could regulate the ecological balance of the intestinal flora and reduce colon injuries induced by 5-FU in CT26 tumour-bearing mice, and the mechanism involved may be associated with the regulation of the NF-κB, Nrf2-ARE and MAPK/P38 pathways.

Graphical abstract: Carboxymethyl pachyman (CMP) reduces intestinal mucositis and regulates the intestinal microflora in 5-fluorouracil-treated CT26 tumour-bearing mice

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Publication details

The article was received on 28 Nov 2017, accepted on 29 Mar 2018 and first published on 14 May 2018


Article type: Paper
DOI: 10.1039/C7FO01886J
Citation: Food Funct., 2018,9, 2695-2704
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    Carboxymethyl pachyman (CMP) reduces intestinal mucositis and regulates the intestinal microflora in 5-fluorouracil-treated CT26 tumour-bearing mice

    C. Wang, S. Yang, L. Gao, L. Wang and L. Cao, Food Funct., 2018, 9, 2695
    DOI: 10.1039/C7FO01886J

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