Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota.

Abstract

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1β, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

• Authors: Jiazhen Wu, Yuxuan Gan, Muxia Li, Liping Chen, Jiali Liang, Jianyi Zhuo, Huijuan Luo, Nan Xu, Xue Wu, Qiduan Wu, Zhixiu Lin, Ziren Su, Yuhong Liu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 124 Pg. 109883 (Apr 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 32004938 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Myd88 protein, rat
• Myeloid Differentiation Factor 88
• NF-kappa B
• Sesquiterpenes
• Tlr2 protein, rat
• Toll-Like Receptor 2
• patchouli alcohol
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (toxicity)
• Dose-Response Relationship, Drug
• Fluorouracil (toxicity)
• Gastrointestinal Microbiome (drug effects)
• Inflammation (chemically induced, prevention & control)
• Intestinal Mucosa (drug effects, pathology)
• Male
• Mucositis (chemically induced, prevention & control)
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sesquiterpenes (pharmacology)
• Toll-Like Receptor 2 (metabolism)