Abstract
Nuclear factor- (erythroid-derived 2) like 2 (Nrf2) is a transcription factor that regulates the expression of a battery of antioxidant, anti-inflammatory, and cytoprotective enzymes including heme oxygenase-1 (Hmox1, Ho-1) and NADPH:quinone oxidoreductase-1 (Nqo1). The isothiocyanate sulforaphane (SF) is widely understood to be the most effective natural activator of the Nrf2 pathway. Falcarinol (FA) is a lesser studied natural compound abundant in medicinal plants as well as dietary plants from the Apiaceae family such as carrot. We evaluated the protective effects of FA and SF (5 mg/kg twice per day in CB57BL/6 mice) pretreatment for one week against acute intestinal and systemic inflammation. The phytochemical pretreatment effectively reduced the magnitude of intestinal proinflammatory gene expression (IL-6, Tnfα/Tnfαr, Infγ, STAT3, and IL-10/IL-10r) with FA showing more potency than SF. FA was also more effective in upregulating Ho-1 at mRNA and protein levels in both the mouse liver and the intestine. FA but not SF attenuated plasma chemokine eotaxin and white blood cell growth factor GM-CSF, which are involved in the recruitment and stabilization of first-responder immune cells. Phytochemicals generally did not attenuate plasma proinflammatory cytokines. Plasma and intestinal lipid peroxidation was also not significantly changed 4 h after LPS injection; however, FA did reduce basal lipid peroxidation in the mesentery. Both phytochemical pretreatments protected against LPS-induced reduction in intestinal barrier integrity, but FA additionally reduced inflammatory cell infiltration even below negative control.
Highlights
The gastrointestinal (GI) tract is the largest interface between the body and the environment, followed by the lung and the integument, with ratios of an estimated surface area approximately 150 : 50 : 1. The small intestine is the majority component of the GI tract; its surface was composed of a single monolayer of intestinal epithelial cells which secrete a glycocalyx matrix and a layer of mucous
Phytochemicals were prepared in 100% ethanol immediately before individual doses were prepared in peanut butter and allowed to evaporate overnight, refrigerated in a light-proof container
We evaluated the effect of phytochemicals on the expression of Nrf2, Keap1, and their responsive genes heme oxygenase-1 (Hmox1) and NADPH:quinone oxidoreductase-1 (Nqo1) in both the intestine and the liver (Figure 6)
Summary
The gastrointestinal (GI) tract is the largest interface between the body and the environment, followed by the lung and the integument, with ratios of an estimated surface area approximately 150 : 50 : 1. The small intestine is the majority component of the GI tract; its surface was composed of a single monolayer of intestinal epithelial cells which secrete a glycocalyx matrix and a layer of mucous. The small intestine is the majority component of the GI tract; its surface was composed of a single monolayer of intestinal epithelial cells which secrete a glycocalyx matrix and a layer of mucous. This delicate barrier performs the diametric roles of digestion and absorption of nutrients and protection against pathogenic microorganisms and innumerable xenobiotic compounds from the environment [1]. Intestinal barrier integrity is a lesser appreciated early deviation from homeostasis that contributes to many intestinal diseases (IBD, IBS, and celiac disease to name a few [5,6,7]) and many other widely divergent pathologies.
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