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 60 μM) 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 40 mg/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.