Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 21, Pages 6707-6715Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm9006164
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Funding
- Prof Francis SK Lau and Mr. William Au Research Fund
- Purapharm International
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Cimicifuga species have been used as traditional medicinal herbs to treat inflammation and symptoms associated with menopause in Asia, Europe, and North America. However, the underlying mechanism of their anti-inflammatory effects remains to be investigated. With bioactivity guided purification involving the use of partitioning extraction and high performance liquid chromatography, we isolated one of the key bioactive constituents from the rhizome extracts of Cimicifuga racemosa. By NMR spectroscopy, the molecule was identified to be cimiracemate A (L). This compound (140 mu M) suppressed the lipopolysaccharide-induced TNF-alpha production in the blood macrophages by 47 +/- 19% and 58 +/- 0% at LIPS concentrations of 1 ng/mL and 10 ng/rnL, respectively. The anti-inflammatory activity of compound 1 may be due to its modulation of a signaling mitogen activated protein kinase and transcription factor nuclear factor-kappaB activities. Compound 1 was found in other Cimicifuga species. Our data indicate that compound 1 or its chemical analogues may have the potential to be further developed as a new class of therapeutic agent.
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