Total saponin of Dioscoreacollettii attenuates MSU crystal‑induced inflammation via inhibiting the activation of the NALP3 inflammasome and caspase‑1 in THP‑1 macrophages.

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 THP-1 macrophages. The viability of THP-1 macrophages was examined using the MTT assay and the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-18 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 THP-1 cells treated with 100 ng/ml phorbol ester, suggesting that monocytic THP-1 cells were successfully differentiated into macrophages. TSD decreased the levels of inflammatory cytokines, including TNF-α, IL-18 and IL-1β, secreted by THP-1 macrophages. As the release of IL-1β and IL-18 is dependent on the NLR family pyrin domain containing 3 (NALP3) inflammasome and caspase-1, the current study investigated the effect of TSD on the aforementioned proteins. The results revealed that TSD decreased the protein levels of NALP3 and apoptosis-associated speck-like, which serve important roles in the assembly of the NALP3 inflammasome. Furthermore, NALP3 inflammasome-related proteins were also decreased by TSD in rotenone induced THP-1 macrophages, TSD inhibited the activation of caspase-1 and rotenone-induced NALP3 inflammasome activation in THP-1 macrophages. The results obtained in the current study revealed that TSD attenuated MSU crystal-induced inflammation by inhibiting rotenone-induced activation of the NALP3 inflammasome and caspase-1, suggesting that these two proteins may be novel targets for the treatment of gouty arthritis.