Methanolic extracts of Capparis ecuadorica iltis inhibit the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophage cells

Abstract

Background: Some species of the caper family are known to possess antibacterial, antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties. However, to date, the therapeutic effects of Capparis ecuadorica Iltis (Capparis L.) have not been studied. Objectives: In this study, we investigated the anti-inflammatory activity of a methanolic extract of C. ecuadorica leaves (MCE) in macrophages. Materials and Methods: Anti-inflammatory responses and mechanisms were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after pretreatment with MCE. Results: In the MCE + LPS-treated group, the relative mRNA levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6) were downregulated and protein levels of IL-6 were also decreased as compared to the vehicle + LPS-treated group. Furthermore, the MCE + LPS-treated group showed reduced levels of reactive oxygen species (ROS) production as compared to the vehicle + LPS-treated group; detection of nitrite concentration revealed nitric oxide (NO) to be the reduced ROS. The expression levels of inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 (COX-2) mRNA and the level of phosphorylation of IκBα were decreased in the MCE + LPS-treated group. In addition, MCE + LPS-treated group showed reduced levels of phosphorylation of MAP kinase in comparison to the vehicle + LPS-treated group. Interestingly, MCE also inhibited other inflammatory mechanisms, namely, endoplasmic reticulum (ER) stress and autophagy. Conclusion: These results indicate that MCE inhibits inflammatory responses through the inhibition of inflammatory cytokines and NO production, iNOS/COX-2 expression and nuclear factor-kappa B (NF-κB) activation, MAPK inhibition, as well as regulation of ER stress and autophagy in LPS-stimulated RAW 264.7 cells.