Cimicifuga and its component actein attenuate acute gouty arthritis by targeting neutrophil activation

Neutrophil infiltration and abnormal activation are key pathological processes in the development of acute gouty arthritis (AGA). Cimicifuga and its components exhibit substantial anti-inflammatory properties and demonstrate therapeutic potential in a range of inflammatory diseases; however, their effects on AGA remain unclear. This study aimed to investigate the anti-arthritic effect of Cimicifuga and actein, and further explore the mechanisms. In the in vitro study, neutrophils were isolated and treated with Cimicifuga-containing serum or actein to investigate their regulatory effects on neutrophil functions. In vivo, AGA murine model was established to investigate the therapeutic efficacy and immunomodulatory mechanisms of Cimicifuga and actein. Our results show that both Cimicifuga-containing serum and actein significantly suppressed neutrophil chemotaxis and enhanced apoptosis under inflammatory conditions, thereby facilitating inflammation resolution. Additionally, their treatment reduced the release of proinflammatory cytokines TNF-α, IL-1β, and IL-6, inhibited reactive oxygen species (ROS) production, and decreased neutrophil extracellular trap (NET) formation. Actein also suppressed the phagocytosis of beads by neutrophils. In vivo, Cimicifuga and actein markedly reduced ankle swelling and histological inflammation in AGA mice, along with a decrease in local inflammatory cytokines. Although the proportion of circulating neutrophils remained unchanged, a notable upregulation of the chemokine CXCL2 was observed in inflamed joints, which was significantly downregulated by Cimicifuga and actein treatment. Moreover, both interventions lowered plasma cell-free DNA (cf-DNA) levels, further indicating NET inhibition. These findings reveal that Cimicifuga and actein ameliorate AGA through multifaceted regulation of neutrophil activities, providing scientific support for their clinical application in AGA management.