Sinomenine alleviates gouty inflammation by inhibiting macrophage M1 polarization and neutrophil extracellular trap formation

Abstract

Gout is a common inflammatory arthropathy characterized by the deposition of monosodium urate (MSU) crystals, leading to severe pain and swelling. Sinomenine (SIN) is the major active component of Sinomenium acutum. SIN has been demonstrated to exert preventive and therapeutic effects on arthritis in cell-based, animal, and clinical studies. The present study focused on the efficacy and role of SIN in relieving symptoms of gouty inflammation in vivo and in vitro. The anti-inflammatory effects of SIN were evaluated in mice with MSU-induced air-pouch via hematoxylin-eosin (HE) staining, and enzyme-linked immunosorbent assay (ELISA). Transcriptomic analysis revealed that SIN modulates a range of inflammatory pathways associated with gout pathogenesis. Notably, the NOD-like receptor pathway and neutrophil extracellular trap (NET) formation were significantly enriched with the occurrence of gout and significantly improved after SIN treatment. THP-1 macrophages were stimulated with PBS or MSU, with or without SIN. Immunofluorescence (IF) and western blotting (WB) results indicated that SIN suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/interleukin-1β (IL-1β) expression. Additionally, SIN inhibited macrophage M1 polarization and NET formation. In summary, SIN ameliorates gouty inflammation, likely by regulating the NLRP3/IL-1β pathway, M1 macrophage polarization, and NET formation. Thus, SIN is a promising drug for treating gout.

Keywords: Gouty inflammation; Macrophage polarization; Neutrophil extracellular traps; Sinomenine.