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

Abstract

In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in Artemisia vestita, 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.

• Authors: Go Oun Kim, Dong Ho Park, Jong-Sup Bae
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 10 (May 10 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 37239882 (Publication Type: Journal Article)

Chemical References

• cirsilineol
• Cyclooxygenase 2
• Heme Oxygenase-1
• Lipopolysaccharides
• NF-E2-Related Factor 2
• NF-kappa B
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Flavones

Topics

• Animals
• Humans
• Mice
• Cyclooxygenase 2 (metabolism)
• Endothelial Cells (metabolism)
• Heme Oxygenase-1 (metabolism)
• Inflammation (drug therapy)
• Lipopolysaccharides (toxicity)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Flavones (pharmacology)