Background Gout is a chronic disease induced by the deposition of monosodium urate. It consists with four stages, hyperuricemia, asymptoms, gout flare and tophaceous gout. Current therapies mainly prevent the flare by using the xanthine oxidase inhibitors, low dose colchicine or uretic agents to keep the level of serum uric acid lower than 6mg/dl. For the flare, the treatment is using steroid or colchicine to control the inflammation and pain. The efficacy of xanthine oxidase inhibitors is very good. But patients have difficulty to go through in the initial stage when the treatment usually causes more flare. The prevention treatment is not benefit for the long term disease outcome and side effects. Recently, the drug development turns to decrease the flare frequency and release the pain at flare-up. The clinical trials showed that the use of IL-1β trap or monoclonal antibody can reduce the number of flares and fast response on pain relief. They are all biologics and inconvenient for long term use and very costly.
Objectives Our goal was to discover candidates for gout flare treatment by screening the herbal extracts with inhibitory activity of IL-1β secretion in cell and further evaluating in the gout animal model.
Methods IL-1β secretion from macrophage cells was stimulated by the monosodium urate crystal and the amount of IL-1β was measured with ELISA. The gout animal model was created by the injection of filtered air to form a pseudosynovial air pouch. The exudates induced by the monosodium urate in the air pouch were analyzed for the cytokines and cells.
Results Anisomeles indica (AG-02) was selected from more than 1000 herbal extracts screening against IL-1β secretion from macrophage cells. The active ingredients of AG-02 were isolated and identified as AG02-RA1 and AG02-RA2. AG-02 ethanol extract and active ingredients AG02-RA1 and AG02-RA2 showed IL-1β inhibitory activity with IC50s of 37±6μg/ml, 4.5±4.6 and 2.2±1.6, respectively. Oral administration of 500mg/kg AG-02 ethanol extract or 6 to 50 mg/kg AG02-RA1 showed both samples could decrease IL-1βsecretion and inflammatory cells infiltration in the air pouch.
Conclusions The results indicate that AG02 and AG02-RA1 confer anti-inflammatory effects by modulation pro-inflammatory cytokines IL-1β production. Both AG-02 and its active principles may be potential candidates for the treatment of gouty arthritis.
Disclosure of Interest None Declared
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