There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ~230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ~125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
The digestive system is endowed with its own, local nervous system, referred to as the enteric nervous system (ENS). Given the varied functions of small intestine, its ENS has developed individualized characteristics relating to motility, secretion, digestion, and inflammation. The ENS regulates the major enteric processes such as immune response, detecting nutrients, motility, microvascular circulation, intestinal barrier function, and epithelial secretion of fluids, ions, and bioactive peptides. Remarkable progress has been made in understanding the signaling pathways in this complex system and how they work. In this article, we focus on recent advances that have led to new insights into small intestinal ENS function and the development of new therapies.