Juglone Suppresses LPS-induced Inflammatory Responses and NLRP3 Activation in Macrophages

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 13; p. 3104
• Main Authors: Kim, Nam-Hun, Kim, Hong-Ki, Lee, Ji-Hak, Jo, Seung-Il, Won, Hye-Min, Lee, Gyeong-Seok, Lee, Hyoun-Su, Nam, Kung-Woo, Kim, Wan-Jong, Han, Man-Deuk
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.07.2020; MDPI
• Subjects: Adenosine triphosphatase; Adenosine triphosphate; Animals; Apoptosis; Arteriosclerosis; Atherosclerosis; Cancer; Caspase-1; Cell activation; Cell Line; Cytokines; Cytotoxicity; Enzymes; IL-18; IL-1β; Infectious diseases; Inflammasomes; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 18; Interleukin-18 - metabolism; Interleukin-1beta - metabolism; Juglone; Lipopolysaccharides; Lipopolysaccharides - toxicity; Macrophages; Macrophages - metabolism; Mice; Naphthoquinones - pharmacology; Nitric oxide; Nitric Oxide - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Oxidative stress; Pathogens; Proteins; Reactive Oxygen Species - metabolism; IL-1β; NLRP3 inflammasome; caspase-1; IL-18; juglone
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25133104

The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome has been implicated in a variety of diseases, including atherosclerosis, neurodegenerative diseases, and infectious diseases. Thus, inhibitors of NLRP3 inflammasome have emerged as promising approaches to treat inflammation-related diseases. The aim of this study was to explore the effects of juglone (5-hydroxyl-1,4-naphthoquinone) on NLRP3 inflammasome activation. The inhibitory effects of juglone on nitric oxide (NO) production were assessed in lipopolysaccharide (LPS)-stimulated J774.1 cells by Griess assay, while its effects on reactive oxygen species (ROS) and NLRP3 ATPase activity were assessed. The expression levels of NLRP3, caspase-1, and pro-inflammatory cytokines (IL-1β, IL-18) and cytotoxicity of juglone in J774.1 cells were also determined. Juglone was non-toxic in J774.1 cells when used at 10 μM ( < 0.01). Juglone treatment inhibited the production of ROS and NO. The levels of NLRP3 and cleaved caspase-1, as well as the secretion of IL-1β and IL-18, were decreased by treatment with juglone in a concentration-dependent manner. Juglone also inhibited the ATPase activities of NLRP3 in LPS/ATP-stimulated J774.1 macrophages. Our results suggested that juglone could inhibit inflammatory cytokine production and NLRP3 inflammasome activation in macrophages, and should be considered as a therapeutic strategy for inflammation-related diseases.