Kjellmaniella crassifolia Reduces Lipopolysaccharide-Induced Inflammation in Caco-2 Cells and Ameliorates Loperamide-Induced Constipation in Mice.

Abstract

Gastrointestinal disorders are widespread globally, with inflammatory diseases being particularly prominent. This study aimed to investigate the effect of Kjellmaniella crassifolia hot water extract (KCH) on lipopolysaccharide (LPS)-induced inflammation in human intestinal epithelial (Caco-2) cells and loperamide-induced constipation in BALB/c mice. The study's findings revealed that KCH dose-dependently increased the cell viability and reduced the NO production by decreasing the iNOS and COX-2 expression in LPS-stimulated Caco-2 cells. Also, KCH downregulated the mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) by regulating the activation of MAPK and NF-κB signaling pathways in LPS-stimulated Caco-2 cells. In addition, KCH increased the expression levels of tight junction proteins, occludin, ZO-1, and claudin-1 in a dose-dependent manner. Furthermore, in vivo study outcomes demonstrated that KCH improved intestinal transit, increased fecal moisture content, and reduced fecal impaction in constipated mice. KCH decreased the mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), thereby increasing the expression levels of intestinal tight junction proteins (occludin, ZO-1, and claudin-1) in the small intestine tissues of the experimental mice. These proteins may help regulate intestinal motility and improve stool passage, thus reducing constipation. These findings suggest that KCH could be a promising functional food ingredient for managing intestinal inflammation, inflammation-related disorders, constipation, and the pathophysiology of constipation.