Inhibition of monosodium urate crystal-induced inflammation by scopoletin and underlying mechanisms.
The present study determined the anti-inflammatory activity of scopoletin in gout air pouch model and revealed the underlying mechanisms by in vitro assays. Monosodium urate (MSU) crystal-induced inflammation in mouse air pouch model, an experimental model for acute gout, was used to assess the efficacy of scopoletin. The neutrophil and mononuclear phagocyte numbers and MPO levels were increased significantly six hours after MSU crystal injection into the air pouch, whereas these changes were inhibited substantially upon scopoletin (100 and 200mg/kg, i.p.) treatment. To get insight into the underlying mechanisms, the in vitro studies were performed to investigate the effects of scopoletin on activation of macrophages and resultant production of inflammatory mediators. The secretions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) were elevated in MSU crystal-stimulated RAW 264.7 cells, and scopoletin (30-300 μM) suppressed the production of all mediators. Moreover, RT-PCR assay and western blot analysis indicated that scopoletin regulated the transcriptional level of these mediators via suppression of NF-κB activation and blockade of MAPK signal pathway. Thus, the results clearly indicated that scopoletin inhibited the monosodium urate crystal-induced inflammation both in vivo and in vitro. In combination with our previous findings that scopoletin shows hypouricemic, anti-angiogenesis and pro-apoptotic activities, this compound may be a potential agent for gout therapy and could serve as a structural base for developing new drugs.
State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Xiujuan
X
Yao
Zuoqi
Z
Ding
Yufeng
Y
Xia
Zhifeng
Z
Wei
Yubin
Y
Luo
Carlos
C
Feleder
Yue
Y
Dai
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006813:Humidity; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D007962:Leukocytes; D008264:Macrophages; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012603:Scopoletin / Q000737:chemistry / Q000494:pharmacology*; D013696:Temperature; D014527:Uric Acid / Q000633:toxicity*
D016207:Cytokines; D012333:RNA, Messenger; D014527:Uric Acid; D009569:Nitric Oxide; D012603:Scopoletin