Gryllus bimaculatus Extract Protects against Lipopolysaccharide-Derived Inflammatory Response in Human Colon Epithelial Caco-2 Cells

SIMPLE SUMMARY: Inflammatory bowel disease (IBD), a potentially life-threatening disease, is characterized by increased tight junction permeability and overproduction of proinflammatory cytokines. The long-term administration of recognized chemotherapeutic agents can cause serious potential side effects. As such, increasing attention has been paid to natural, low-toxicity products with anti-inflammatory properties for treating IBD. We assessed the potential utility of the edible cricket species Gryllus bimaculatus for anti-inflammatory and cytoprotective effects in the human epithelial cell line Caco-2, following treatment with an inflammatory lipopolysaccharide stimulus. We found that aqueous ethanolic G. bimaculatus extract (AE-GBE) treatment increased cell viability and significantly reduced inflammatory mediators. Moreover, AE-GBE significantly reduced inflammatory cytokine expression levels, intestinal epithelial permeability, and related tight junction protein expression levels. In conclusion, AE-GBE can protect epithelial cells from lipopolysaccharide-induced impaired barrier integrity by increasing tight junction proteins and preventing various inflammatory mediators. These results may be used to pursue further use of natural insect extracts in treating IBD. ABSTRACT: Increased tight junction permeability and overproduction of proinflammatory cytokines are crucial pathophysiological mechanisms in inflammatory bowel disease (IBD). This study evaluated anti-inflammatory effects of aqueous ethanolic Gryllus bimaculatus extract (AE-GBE) against intestinal permeability on lipopolysaccharide (LPS)-treated Caco-2 cells. Treatment with AE-GBE increased cell viability and significantly reduced inflammatory mediators such as nitric oxide and LPS-induced reactive oxidative stress. LPS increased the expression levels of iNOS, Cox-2, and 4-hydroxylnonenal; however, these levels were attenuated by AE-GBE treatment. Moreover, the mRNA and protein expression levels of the inflammatory cytokines TNFα, IL-6, IL-1β, and IFNγ were increased by LPS, but were significantly reduced by AE-GBE treatment. Intestinal epithelial permeability and the related expression of the proteins Zoula ocludence-1, occludin, and claudin-1 was increased by LPS treatment, and this effect was significantly reduced by AE-GBE treatment. The reduction in AMPK phosphorylation in LPS-treated Caco-2 cells was reversed in activation by co-treatment with AE-GBE. In conclusion, AE-GBE can protect epithelial cells from LPS-induced impaired barrier integrity by increasing tight junction proteins and preventing various inflammatory mediators. Thus, AE-GBE has the potential to improve inflammation-related diseases, including IBD, by inhibiting excessive production of inflammation-inducing mediators.