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

J Agric Food Chem. 2023 Aug 30;71(34):12715-12729. doi: 10.1021/acs.jafc.3c03195. Epub 2023 Aug 15.

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.

Keywords: antioxidant, anti-inflammation; flavonoids; inflammatory bowel diseases; zinc ions.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants* / metabolism
  • Colitis* / drug therapy
  • Colon / metabolism
  • Dextran Sulfate / metabolism
  • Disease Models, Animal
  • Hydrogen Peroxide / metabolism
  • Intestinal Mucosa / metabolism
  • Lipopolysaccharides / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Reactive Oxygen Species / metabolism
  • Rutin / metabolism
  • Zinc / metabolism

Substances

  • Antioxidants
  • Rutin
  • Reactive Oxygen Species
  • Zinc
  • Hydrogen Peroxide
  • Lipopolysaccharides
  • Anti-Inflammatory Agents
  • Dextran Sulfate