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

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

Author information

1
School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
2
Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China.
3
School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China.
4
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
5
Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China; Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
6
School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China. Electronic address: fengli81@163.com.
7
School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Innovation Center for Marine Drug Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China. Electronic address: wbli92128@ouc.edu.cn.

Abstract

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

PMID:
31022552
DOI:
10.1016/j.ejmech.2019.04.031
[Indexed for MEDLINE]

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