1. Synthesis and biological evaluation of pyranoisoflavone derivatives as anti-inflammatory agents.
- Author
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Zhe Wei, Youzhe Yang, Caifeng Xie, Chunyan Li, Guangcheng Wanga, Liang Ma, Mingli Xiang, Jian Sun, Yuquan Wei, and Lijuan Chen
- Subjects
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RHEUMATOID arthritis , *ALTERNATIVE medicine , *ANIMAL experimentation , *ANTI-inflammatory agents , *BIOLOGICAL models , *BIOPHYSICS , *DOSE-effect relationship in pharmacology , *RESEARCH methodology , *RATS , *TUMOR necrosis factors , *PHYTOCHEMICALS , *DESCRIPTIVE statistics , *IN vitro studies , *CHEMICAL inhibitors , *PHARMACODYNAMICS , *PREVENTION - Abstract
In this paper, barbigerone (1a) and its twenty-seven related structural analogues were synthesized via complementary synthetic routes and their anti-inflammatory effects on the expression of TNF-α in LPS-stimulated splenocytes were evaluated. Among these compounds, 1a, 1d, 1f and 1g were found to remarkably inhibit TNF-α production. Furthermore, 1g showed the most potent and dose-dependent manner inhibitory effect on TNF-α release, with better IC50 value (3.58 μM) than barbigerone (8.46 μM). Oral administration of 1g at 20 mg/kg/day for two weeks obviously demonstrated protective effect in adjuvant-induced arthritis models as evaluated by clinical score of paws, and histological examination of joint tissues from rats. Mechanism studies on mRNA and protein level suggested that 1g inhibited the TNF-α production via depressing TNF-α converting enzyme (TACE) mRNA expression. In conclusion, these data show 1g with potential therapeutic effects as an anti-inflammatory agent. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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