The Regulatory Effects of Licochalcone A on the Intestinal Epithelium and Gut Microbiota in Murine Colitis

Abstract

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.

Chalcones and Gastrointestinal Cancers: Experimental Evidence

“…Chalcones, such as LiA, are important inhibitors of TLR4-mediated NF-κB activation, with higher accumulation in Caco-2 cells [ 154 ]. Licochalcone A exudes anti-UC activity, in part by blocking the MAPK pathway [ 155 ]. Another natural chalcone, ISL, reduces the incidence of colitis that is associated with colorectal cancer through the modulation of gut microbiota and pro-inflammatory cytokines [ 156 ].…”

Cymbopogon citratus (DC.) Stapf aqueous extract ameliorates loperamide-induced constipation in mice by promoting gastrointestinal motility and regulating the gut microbiota

“…The normal intestinal mucosal barrier is mainly composed of four parts: mechanical barrier, chemical barrier, immune barrier and biological barrier. The occludin family, claudin family and ZO family are important protein molecules that constitute the tight junctions between cells ( Zhang J. et al, 2021 ). The basic structure of the chemical barrier is the mucus layer, which is mainly composed of mucus and other substances secreted by the intestinal epithelium ( Lu et al, 2021 ).…”

Traditional Chinese medicine treats ulcerative colitis by regulating gut microbiota, signaling pathway and cytokine: Future novel method option for pharmacotherapy

“…In addition, the main gut microflora involved in the therapeutic effects of licochalcone A on DSS-induced colitis include ruminococcaceae, defluviitaleaceae, streptococcaceae, moraxellaceae, akkermansiaceae, bacillaceae, and bifidobacteriales, etc. Licochalcone A could alleviate UC by increasing the relative abundance of beneficial gut barrier-beneficial bacteria such as akkermansiaceae and decreasing the levels of gut barrier-harmful bacteria such as prevotellaceae and bacillaceae [ 71 ].…”