Peroxyauraptenol Inhibits Inflammation and NLRP3 Inflammasome Activation by Inhibiting Reactive Oxygen Species Generation and Preserving Mitochondrial Integrity

J Agric Food Chem. 2015 Feb 4;63(4):1210-1219. doi: 10.1021/jf5054436. Epub 2015 Jan 22.

Abstract

Peroxyauraptenol (PXT) is a peroxide-containing coumarin compound isolated from the seeds of Cnidium monnieri. PXT exerts anti-inflammatory activities, as it reduces the levels of inducible nitric oxide synthase, nitric oxide, IL-6, and NLRP3 inflammasome-derived IL-1β in lipopolysaccharide-activated macrophages. PXT also exerts anti-inflammatory activity by reducing reactive oxygen species generation (including mitochondrial), mitogen-activated protein kinase, protein kinase C-α/δ phosphorylation, and the release of mitochondrial DNA into the cytosol. In addition, PXT suppresses the phagocytic activity of macrophages and IL-1β secretion by Klebsiella pneumoniae-infected macrophages. The unique peroxide group is important for the anti-inflammatory activity of PXT, as this activity is reduced when the peroxide group is replaced by a hydroxyl group. These findings suggest that PXT may be a candidate for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation-related diseases.

Keywords: NLRP3 inflammasome; inflammation; mitochondria; peroxyauraptenol; reactive oxygen species.