Alpinia katsumadai Hayata Volatile
Oil Is Effective in Treating 5‑Fluorouracil-Induced Mucositis
by Regulating Gut Microbiota and Modulating the GC/GR Pathway and
the mPGES-1/PGE2/EP4 Pathways
posted on 2023-10-06, 13:06authored byDong Liu, Fei Tang, Li Zhang, Jing-Nan Zhang, Xiao-Lan Zhao, Li-Yue Xu, Cheng Peng, Hui Ao
This
study was aimed to investigate the therapeutic effect and
mechanism of AKHO on 5-fluorouracil (5-FU)-induced intestinal mucositis
in mice. Mouse body weight, diarrhea score, and H&E staining were
applied to judge the therapeutic effect of AKHO. 16S rDNA and nontargeted
metabolomics have been used to study the mechanism. WB, ELISA, and
immunohistochemistry were adopted to validate possible mechanisms.
The results demonstrated that AKHO significantly reduced diarrhea
scores and intestinal damage induced by 5-FU in mice. AKHO lowered
the serum levels of LD and DAO, and upregulated the expressions of
ZO-1 and occludin in the ileum. Also, AKHO upregulated the abundance
of Lactobacillus in the gut and suppressed KEGG pathways
such as cortisol synthesis and secretion and arachidonic acid metabolism.
Further validation studies indicated that AKHO downregulated the expressions
of prostaglandin E2 (PGE2), microsomal prostaglandin E synthase-1
(mPGES-1), and PGE2 receptor EP4, as well as upregulated the expression
of glucocorticoid (GC) receptor (GR), leading to improved intestinal
epithelial barrier function. Taken together, AKHO elicited protective
effects against 5-FU-induced mucositis by regulating the expressions
of tight junction proteins via modulation of GC/GR and mPGES-1/PGE2/EP4
pathway, providing novel insights into the utilization and development
of this pharmaceutical/food resource.