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.