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

Abstract

<jats:p>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 (p &lt; 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.</jats:p>

Effects of REDOX in Regulating and Treatment of Metabolic and Inflammatory Cardiovascular Diseases

“…It is worth mentioning that a recent research found that colchicine, which is a drug widely used in the treatment of nonspecific inflammation, could combine with cholesterol crystal (CC), an important pathological marker for the vulnerability of atherosclerotic plaques [73]. This combination can reduce the intake of cholesterol crystals by endothelial cells, thus attenuating the cellular oxidative stress and endothelial cell prolapse by regulating the AMPK/SIRT1 signaling pathway [74].…”

Induction of Oxidative Stress and Mitochondrial Dysfunction by Juglone Affects the Development of Bovine Oocytes

“…In addition, juglone exhibits antifungal (e.g., Aspergillus and Penicillium ), antibacterial (e.g., Escherichia coli , Staphylococcus aureus , Bacillus subtilis , and Helicobacter pylori ), antiviral, and antiparasitic activities [ 4 , 7 , 8 ]. However, juglone also suppressed lipopolysaccharides-induced inflammatory responses and NLRP3 inflammasome activation in tumor-derived J774.1 cells [ 9 ]. For these reasons, it has long been used in traditional medicine against various health conditions, including gastrointestinal disorders, cancers, allergies, and different microbial infections [ 6 ].…”

NLRP3 İnflamazom Aktivasyon ve Düzenleme Mekanizmalarına Genel Bir Bakış

“…İmmün hücreler için, NLRP3 aktivatörlerinin mevcudiyeti tek başına inflamazom oluşumunu ve aktivasyonunu uyarmak için yetersizdir, bunun için bir hazırlama (priming) sinyali (sinyal 1) gereklidir 3 . Makrofaj ya da glia hücrelerinde bulunan PRR'ler tarafından (TLR ya da NLR'ler), PAMP'ların ve DAMP'ların tanınması sonucu enflamasyonu indükleyen NF-κB sinyalizasyonun aktivasyonu ve enflamatuvar sitokinlerin salınması gerçekleşir 12 . İlk sinyal sonucu, IL-6, TNF-α gibi proenflamatuvar sitokinlerin gen transkripsiyonları artar ve doğrudan salınımları gerçekleşir.…”