Anti-inflammatory Ellagitannins from Cleidion brevipetiolatum for the Treatment of Rheumatoid Arthritis
Anti-inflammatory Ellagitannins from Cleidion brevipetiolatum for the Treatment of Rheumatoid Arthritis
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来自 Cleidion brevipetiolatum 的抗炎鞣花单宁用于治疗类风湿性关节炎
DOI：
10.1021/acs.jnatprod.8b00984
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发表时间：
2019-09-01
影响因子：
5.1
通讯作者：
Chen, Li-Juan
中科院分区：
文献类型：
--
作者：
Zhao, Min;Yuan, Xue;Chen, Li-Juan
Six new ellagitannins, brevipetins B-G (5 and 7-11), and a new phenolic glucoside, brevipetin A (4), along with six known compounds were isolated from the traditional Chinese medicinal plant Cleidion brevipetiolatum. Their structures and absolute configurations were determined by spectroscopic analyses, chemical methods, and TD-DFT-ECD calculations. Compounds 5-11 exhibited NO inhibitory effects with IC50 values of 1.9-8.2 mu M, and 9 showed the most potent inhibitory effect (IC50: 1.9 mu M). An in vivo anti-inflammatory assessment of 9 showed that it exerts therapeutic effects in both the carrageenan-induced rat paw edema and collagen-induced arthritis (CIA) models at 50 mg/kg oral administration. The enhanced protein and mRNA expression levels of iNOS (inducible nitric oxide synthase) and COX-2 (cyclo-oxygenase-2) in LPS-stimulated RAW 264.7 cells were dose-dependently suppressed by 9. An anti-inflammatory mechanistic study revealed that 9 suppressed NF-kappa B activity by inhibiting I kappa B alpha phosphorylation and blocking translocation of p65 from the cytosol to the nucleus. Therefore, 9 might have the potential to be developed as a lead compound for relieving rheumatoid arthritis.
