Development of M10, myricetin-3-O-β-d-lactose sodium salt, a derivative of myricetin as a potent agent of anti-chronic colonic inflammation

Eur J Med Chem. 2019 Jul 15:174:9-15. doi: 10.1016/j.ejmech.2019.04.031. Epub 2019 Apr 16.


Myricetin is a natural dietary flavonoid compound with multiple activities, such as anti-oxidant, anti-inflammatory, anti-carcinogenic and anti-proliferative effects. However, myricetin exhibited substantial limitations, such as poor water-solubility, and low stability in body when it was administrated by oral. To solve these problems, we designed and synthesized a series of derivatives based on the structure of myricetin. M10 was produced by adding a hydrophilic glycosylation group and then forming a sodium salt derivative, which exhibited excellent water-solubility (>100 mg/mL), and better stability in Wistar rat plasma and liver microsomes. In vivo study, M10 exhibited higher efficacy than myricetin and mesalazine in a dextran sulfate sodium (DSS) induced mice model with ulcerative colitis. In addition, M10 also exhibited high safety (LD50 > 5 g/kg) in mice. Based on these results, M10 could be developed as a potential therapeutic agent for treatment of ulcerative colitis.

Keywords: Dextran sodium sulfate; Glycosylation; Inflammatory bowel disease; Myricetin; Ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use*
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colon / pathology
  • Dextran Sulfate
  • Drug Stability
  • Female
  • Flavonoids / chemical synthesis
  • Flavonoids / chemistry
  • Flavonoids / pharmacokinetics
  • Flavonoids / therapeutic use*
  • Glycosylation
  • Half-Life
  • Lactose / analogs & derivatives*
  • Lactose / chemical synthesis
  • Lactose / pharmacokinetics
  • Lactose / therapeutic use*
  • Male
  • Mice, Inbred C57BL
  • Microsomes, Liver / metabolism
  • Rats, Wistar
  • Solubility


  • Anti-Inflammatory Agents
  • Flavonoids
  • Dextran Sulfate
  • Lactose