Anti-inflammatory Ellagitannins from Cleidion brevipetiolatum for the Treatment of Rheumatoid Arthritis
- J Nat Prod. 2019 Sep 27;82(9):2409-2418. doi: 10.1021/acs.jnatprod.8b00984.
- 1. Laboratory of Natural Product Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital , Sichuan University , Chengdu 610041 , People's Republic of China.
- 2. The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, State Key Laboratory, Breeding Base of Systematic Research Development and Utilization of Chinese Medicine Resources, School of Pharmacy , Chengdu University of Traditional Chinese Medicine , Chengdu 611137 , People's Republic of China.
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 μM, and 9 showed the most potent inhibitory effect (IC50: 1.9 μM). 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 (cyclooxygenase-2) in LPS-stimulated RAW 264.7 cells were dose-dependently suppressed by 9. An anti-inflammatory mechanistic study revealed that 9 suppressed NF-κB activity by inhibiting IκBα 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.