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Scopoletin induces apoptosis of fibroblast‐like synoviocytes from adjuvant arthritis rats by a mitochondrial‐dependent pathway
Author(s) -
Li Ying,
Dai Yue,
Liu Mei,
Pan Rong,
Luo Yubin,
Xia Yufeng,
Xia Xiaofeng
Publication year - 2009
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20314
Subject(s) - scopoletin , apoptosis , chemistry , pharmacology , rheumatoid arthritis , cancer research , medicine , biochemistry , pathology , alternative medicine
Scopoletin is a naturally occurring coumarin compound found in many medicinal plants, such as Erycibe obtusifolia Benth and Aster tataricus . Our previous studies have demonstrated that this compound could ameliorate adjuvant‐induced arthritis in a rat model of human rheumatoid arthritis (RA). Since the proliferation of fibroblast‐like synoviocytes (FLS) plays a pivotal role in the formation and growth of pannus, which leads to subsequent joint destruction in RA, we examined the effects of scopoletin on FLS apoptosis. Primary FLS from adjuvant arthritis rats were purified and cultured, and then treated with increasing concentrations of scopoletin (250, 500, 1,000 µM) for 24 h. Scopoletin decreased the viability of FLS in a dose‐dependent manner and remarkably induced their apoptosis, as revealed by Hochest 33258 staining and flow cytometry analysis. Further experiments showed that scopoletin activated caspase‐3, depolarized mitochondrial membrane potential, regulated expression of bcl‐2 family members, and reduced the activation of NF‐κB proteins. These results indicated that scopoletin induced apoptosis of FLS through a mitochondrial‐dependent pathway, which may be mediated by inhibition of NF‐κB activation and promotion of caspase‐3 activation. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.