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

• Main Authors: Nam-Hun Kim, Hong-Ki Kim, Ji-Hak Lee, Seung-Il Jo, Hye-Min Won, Gyeong-Seok Lee, Hyoun-Su Lee, Kung-Woo Nam, Wan-Jong Kim, Man-Deuk Han
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Molecules
• Subjects: juglone; NLRP3 inflammasome; caspase-1; IL-1β; IL-18
• Online Access: https://www.mdpi.com/1420-3049/25/13/3104

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 (<i>p</i> < 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.