Protective Effects of Cirsilineol against Lipopolysaccharide-Induced Inflammation; Insights into HO-1, COX-2, and iNOS Modulation

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8537
• Main Authors: Kim, Go Oun, Park, Dong Ho, Bae, Jong-Sup
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10-05-2023; MDPI
• Subjects: Analysis; Animal models; Animals; Anti-inflammatory agents; Antioxidants; Artemisia vestita; Cancer; Chronic obstructive pulmonary disease; cirsilineol; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Endothelial cells; Endothelial Cells - metabolism; endothelium; Enzymes; Flavones - pharmacology; Genes; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - metabolism; Humans; Inflammation; Inflammation - drug therapy; Inflammatory diseases; iNOS; Lipopolysaccharides; Lipopolysaccharides - toxicity; Mice; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Nuclear transport; p-STAT-1; Phosphorylation; Prostaglandin E2; Prostaglandins E; Proteins; Regulatory sequences; RNA-mediated interference; Signal transduction; Stat1 protein; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Umbilical vein; South Korea; endothelium; iNOS; p-STAT-1; cirsilineol
• DOI: 10.3390/ijms24108537
• EISSN: 1422-0067
• ISSN: 1422-0067; 1661-6596

In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in
, were examined on lipopolysaccharide (LPS)-induced inflammatory responses. CSL was found to have antioxidant, anticancer, and antibacterial properties, and was lethal to many cancer cells. We assessed the effects of CSL on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). We also examined the effects of CSL on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the pulmonary histological status of LPS-injected mice. The results showed that CSL increased HO-1 production, inhibited luciferase-NF-κB interaction, and reduced COX-2/PGE2 and iNOS/NO levels, leading to a decrease in signal transducer and activator of transcription (STAT)-1 phosphorylation. CSL also enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and reduced IL-1β expression in LPS-treated HUVECs. We found that CSL's suppression of iNOS/NO synthesis was restored by inhibiting HO-1 through RNAi. In the animal model, CSL significantly decreased iNOS expression in the pulmonary biostructure, and TNF-α level in the bronchoalveolar lavage fluid. These findings indicate that CSL has anti-inflammatory properties by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, CSL may have potential as a candidate for developing new clinical substances to treat pathological inflammation.