PUBLICATION

Sinomenine Hydrochloride Ameliorates Fish Foodborne Enteritis via α7nAchR-Mediated Anti-Inflammatory Effect Whilst Altering Microbiota Composition

Authors

Xie, J., Li, M., Ye, W., Shan, J., Zhao, X., Duan, Y., Liu, Y., Unger, B.H., Cheng, Y., Zhang, W., Wu, N., Xia, X.Q.

ID

ZDB-PUB-211214-32

Date

2021

Source

Frontiers in immunology 12: 766845 (Journal)

Registered Authors

Xia, Xiao-Qin

Keywords

SBMIE, anti-inflammation, microbiota, sinomenine hydrochloride, zebrafish, ?7nAChR

MeSH Terms

Animal Feed/analysis
Gene Expression Profiling/methods
Binding Sites/genetics
Gene Ontology
Morphinans/metabolism
Morphinans/pharmacology*
Anti-Inflammatory Agents/metabolism
Anti-Inflammatory Agents/pharmacology
Intestinal Mucosa/drug effects
Intestinal Mucosa/metabolism
Cytokines/genetics
Cytokines/metabolism
Molecular Docking Simulation
Fish Diseases/genetics
Fish Diseases/metabolism
Fish Diseases/prevention & control*
alpha7 Nicotinic Acetylcholine Receptor/agonists
alpha7 Nicotinic Acetylcholine Receptor/genetics*
alpha7 Nicotinic Acetylcholine Receptor/metabolism
Microbiota/drug effects*
Microbiota/genetics
Enteritis/genetics
Enteritis/metabolism
Enteritis/prevention & control*
Animals
Diet
Animals, Genetically Modified
CD4-Positive T-Lymphocytes/drug effects
CD4-Positive T-Lymphocytes/metabolism
Zebrafish/genetics*
Zebrafish/metabolism
Zebrafish Proteins/agonists
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism

PubMed

34887862 Full text @ Front Immunol

Abstract

Foodborne intestinal inflammation is a major health and welfare issue in aquaculture. To prevent enteritis, various additives have been incorporated into the fish diet. Considering anti-inflammatory immune regulation, an effective natural compound could potentially treat or prevent intestinal inflammation. Our previous study has revealed galantamine's effect on soybean induced enteritis (SBMIE) and has highlighted the possible role of the cholinergic anti-inflammatory pathway in the fish gut. To further activate the intestinal cholinergic related anti-inflammatory function, α7nAchR signaling was considered. In this study, sinomenine, a typical agonist of α7nAChR in mammals, was tested to treat fish foodborne enteritis via its potential anti-inflammation effect using the zebrafish foodborne enteritis model. After sinomenine's dietary inclusion, results suggested that there was an alleviation of intestinal inflammation at a pathological level. This outcome was demonstrated through the improved morphology of intestinal villi. At a molecular level, SN suppressed inflammatory cytokines' expression (especially for tnf-α) and upregulated anti-inflammation-related functions (indicated by expression of il-10, il-22, and foxp3a). To systematically understand sinomenine's intestinal effect on SBMIE, transcriptomic analysis was done on the SBMIE adult fish model. DEGs (sinomenine vs soybean meal groups) were enriched in GO terms related to the negative regulation of lymphocyte/leukocyte activation and alpha-beta T cell proliferation, as well as the regulation of lymphocyte migration. The KEGG pathways for glycolysis and insulin signaling indicated metabolic adjustments of α7nAchR mediated anti-inflammatory effect. To demonstrate the immune cells' response, in the SBMIE larva model, inflammatory gatherings of neutrophils, macrophages, and lymphocytes caused by soybean meal could be relieved significantly with the inclusion of sinomenine. This was consistent within the sinomenine group as CD4⁺ or Foxp3⁺ lymphocytes were found with a higher proportion at the base of mucosal folds, which may suggest the Treg population. Echoing, the sinomenine group's 16s sequencing result, there were fewer enteritis-related TM7, Sphingomonas and Shigella, but more Cetobacterium, which were related to glucose metabolism. Our findings indicate that sinomenine hydrochloride could be important in the prevention of fish foodborne enteritis at both immune and microbiota levels.

Genes / Markers

Figures