ABSTRACT
Total saponins extracted from Dioscorea collettii (TSD), extracts of the Chinese herb Dioscorea, are thought to exhibit therapeutic benefit in gouty arthritis. However, its exact mechanism remains unclear. The current study aimed to elucidate the underlying mechanisms by investigating the effects of TSD on the inflammation induced by monosodium urate (MSU) crystals in THP1 macrophages. The viability of THP1 macrophages was examined using the MTT assay and the levels of inflammatory cytokines, including interleukin (IL)1ß, IL18 and tumor necrosis factor (TNF)α, released by the cells were quantitatively measured using ELISA kits. The results revealed that the protein level of cluster of differentiation 11b increased in THP1 cells treated with 100 ng/ml phorbol ester, suggesting that monocytic THP1 cells were successfully differentiated into macrophages. TSD decreased the levels of inflammatory cytokines, including TNFα, IL18 and IL1ß, secreted by THP1 macrophages. As the release of IL1ß and IL18 is dependent on the NLR family pyrin domain containing 3 (NALP3) inflammasome and caspase1, the current study investigated the effect of TSD on the aforementioned proteins. The results revealed that TSD decreased the protein levels of NALP3 and apoptosisassociated specklike, which serve important roles in the assembly of the NALP3 inflammasome. Furthermore, NALP3 inflammasomerelated proteins were also decreased by TSD in rotenone induced THP1 macrophages, TSD inhibited the activation of caspase1 and rotenoneinduced NALP3 inflammasome activation in THP1 macrophages. The results obtained in the current study revealed that TSD attenuated MSU crystalinduced inflammation by inhibiting rotenoneinduced activation of the NALP3 inflammasome and caspase1, suggesting that these two proteins may be novel targets for the treatment of gouty arthritis.