Parthenolide Ameliorated Gout-Like Inflammation by Inhibiting Activation of NLRP3 Inflammasome

Objective Crystals of monosodium urate (MSU) are the cause of gout, a common inflammatory disease. Parthenolide (Par), sesquiterpene lactone, derived from feverfew (Pyrethrum parthenium), possesses potent analgesic, anti-inflammatory, and anticancer properties. However, it remains elusive whether and how Par modulates gout. This research was designed to explore the therapeutic effect and mechanism of Par in acute gout. Methods Chondrocytes from rat knee joint and mouse peritoneal macrophages (MPMs) were stimulated by lipopolysaccharide (LPS) plus MSU. Combination of yeast extract (YE) with oxygen oxyazine (OXO) was administered to mice to simulate hyperuricemia. MSU crystals were injected into the mice’s paws or subcutaneously into the mice’s backs to establish acute gouty models. Results Par blocked the activation of NOD-Like Receptor Pyrin Domains 3 (NLRP3) inflammasome by reducing the expression and release of inflammatory mediators in gouty mice and LPS plus MSU-stimulated MPMs, LPS plus MSU-stimulated chondrocytes as well. Par also promoted phagocytosis abilities of MPMs and chondrocytes to reduce inflammation. In addition, Par dose-dependently reduced the serum levels of uric acid (UA), xanthine oxidase (XOD), creatinine (CRE), and blood urea nitrogen (BUN) and ameliorated renal injury in mice with hyperuricemia. Conclusion Par ameliorated uric acid metabolism disorders of hyperuricemia, and improved acute gout-like inflammation through the inhibition of NLRP3 inflammasome activation, indicating that Par may be a promising candidate for gout-targeted therapy.