Olive secoiridoid oleuropein and its semisynthetic acetyl-derivatives reduce LPS-induced inflammatory response in murine peritoneal macrophages via JAK-STAT and MAPKs signaling pathways

Abstract

The present study was designed to investigate the potential anti-inflammatory, antioxidant and immunomodulatory activities of three new derivatives from OL in lipopolysaccharide (LPS)-induced mouse peritoneal macrophages in comparison with natural OL. Nitrites levels were analyzed by Griess method and intracellular reactive oxygen species (ROS) by fluorescence analysis. The levels of cytokines were evaluated by ELISA. The protein expression of cyclo-oxigenase (COX)-2), inducible nitric oxide synthase (iNOS), janus kinase/signal transducer activator of transcription (JAK/STAT) pathway (pSTAT3), haem-oxigenase 1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and MAPKS activation were determined by Western blot. The mechanisms underlying these protective effects could be related to the activation of Nrf2/HO-1 pathway and inhibition of both JAK-STAT and MAPKs signalling pathways. We conclude that OL and new OL acylated-derivatives exhibited immunomodulatory effects and thus, may offer a new promising therapeutic strategy in the management of immune mediated-inflammatory diseases.

Keywords

• HO-1
• LPS
• Macrophage
• Nrf2
• Oleuropein
• ROS