Inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate crystal-induced inflammation

Toxicology and Applied Pharmacology
Yanzhuo LiuJing Yang

Abstract

Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase-1 (mPGES-1)-derived eicosanoids play an essential role in human inflammatory disorders. Here, we investigated whether inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate (MSU) crystal-induced inflammation. Virtual screening assay and in vitro enzyme inhibition assay showed that leonurine was a potential inhibitor of COX-2, mPGES-1 and 5-LOX. Compared with COX-2 inhibitor celecoxib, leonurine (30 mg/kg) significantly decreased ankle perimeter, gait score and neutrophil number in synovial fluid in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, mPGES-1 and 5-LOX and production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the synovial fluid macrophages. In addition, leonurine decreased representative M1 marker (iNOS and CD86) expression, NLRP3 inflammasome activation and M1 cytokine (TNF-α and IL-1β) production. In the in vitro cultured RAW264.7 and human monocyte-derived macrophages (MDMs), blockade of COX-2/mPGES-1 and 5-LOX by leonurine inhibited macrophage M1 polarization and NLRP3 inflammasome activation in response to MSU crystals, and thus down-regulated...Continue Reading

Citations

Dec 29, 2018·The Journal of Pharmacology and Experimental Therapeutics·Honglin TangJing Yang
May 24, 2019·BioMed Research International·Radu Claudiu FierascuCristina Elena Dinu-Pirvu
Jul 22, 2020·Molecular Nutrition & Food Research·Maria WallertStefan Lorkowski
Dec 18, 2018·Journal of Cellular and Molecular Medicine·Min JinYanyun Zhang
Feb 24, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Perihan A ElzahharAhmed F El-Yazbi

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