Zinc-Rutin Particles Ameliorate DSS-Induced Acute and Chronic Colitis via Anti-inflammatory and Antioxidant Protection of the Intestinal Epithelial Barrier.

Abstract

In patients suffering from inflammatory bowel diseases (IBDs), the immune system is disrupted and the intestinal barrier function is compromised. Here, six zinc-flavonoid particles were produced by one-step reaction via changing flavonoids (myricetin, quercetin, and rutin) and solvent (water and ethanol), and then their cytocompatibility and ability to scavenge H2O2, free radicals, and LPS-induced ROS were compared. Zinc-rutin particles (W-ZnRT) composed of rutin (78.92 wt %), Na12[ZnPO4]12·12H2O (6.76 wt %), and crystal water were screened out because W-ZnRT exhibited 80.8 ± 15% cell viability against RAW264.7, could rapidly scavenge 78.1 ± 1% of H2O2 and 71.6 ± 2% of DPPH within 30 min, and reduced LPS-increased intracellular ROS to normal levels. In addition, the therapeutic effects of rutin and W-ZnRT were also compared in dextran sulfate sodium (DSS)-induced acute and chronic colitis in mice. W-ZnRT was superior to rutin alone in chronic colitis (n = 9), although they were equally effective in acute colitis (n = 7). Compared to rutin, 11 oral doses of W-ZnRT (40 mg kg-1) significantly improved intestinal permeability (p = 0.0299) and colon length (p = 0.0025), reduced intestinal proinflammatory factors (IL-6, IL-1β, and TNF-α), and upregulated tight junction proteins to maintain intestinal barrier function. Taken together, these results identified W-ZnRT as an efficient and safe therapeutic strategy for IBD.