Doliroside A attenuates monosodium urate crystals-induced inflammation by targeting NLRP3 inflammasome

Abstract

Our previous study demonstrates that Dolichos falcata Klein (DF) ameliorates the gouty arthritis induced by monosodium urate (MSU) crystals, and one of the active components, doliroside A, contributed to the anti-gouty arthritis effect of DF according to the in vitro study. However, there is still little known about the potential beneficial effects and possible mechanism of action of doliroside A on gouty arthritis. Here, we investigated the underlying mechanism of action of doliroside A in vitro and the anti-inflammatory effects of doliroside A in vivo. Bone-marrow-derived macrophages were treated with doliroside A before or after lipopolysaccharide (LPS) and then stimulated with MSU crystals, nigericin and adenosine triphosphate (ATP). The expressions of proteins related to activation of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome were analyzed. The results manifested that doliroside A (15, 30, 45 and 60μM) suppressed both LPS-induced priming and inflammasome activation in macrophages. Moreover, doliroside A was administered to the rats treated by MSU crystals. The results demonstrated that doliroside A (10, 20 and 40mg/kg) ameliorated the symptoms of gouty arthritis, decreased the levels of pro-inflammatory cytokines, and inhibited the expressions of caspase-1 and pro-interleukin-1β (pro-IL-1β) proteins in MSU crystals-treated rats. These findings indicate that doliroside A exhibits a prominent effect on ameliorating gouty arthritis induced by MSU crystals. The action of doliroside A on gouty arthritis exerts via inhibiting the activation of caspase-1 and IL-1β secretion by affecting both LPS-induced priming and inflammasome activation.