Microsomal Prostaglandin E Synthase 1 (mPGES-1) is the key enzyme for the generation of the pro-inflammatory lipid mediator prostaglandin E (PGE), which contributes to several pathological features of many diseases. Inhibition of mPGES-1 has been shown to be a safe and effective therapeutic strategy in various pre-clinical studies. In addition to reduced PGE formation, it is also suggested that the potential shunting into other protective and pro-resolving prostanoids may play an important role in resolution of inflammation. In the present study, we analysed the eicosanoid profiles in four in vitro inflammation models and compared the effects of mPGES-1 inhibition with those of cyclooxygenase-2 (Cox-2) inhibition. Our results showed a marked shift to the PGD pathway under mPGES-1 inhibition in A549 cells, RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs), whereas enhanced prostacyclin production was observed in rheumatoid arthritis synovial fibroblasts (RASFs) treated with an mPGES-1 inhibitor. As expected, Cox-2 inhibition completely suppressed all prostanoids. This study suggests that the therapeutic effects of mPGES-1 inhibition may be mediated by modulation of other prostanoids in addition to PGE reduction.
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http://dx.doi.org/10.1016/j.prostaglandins.2023.106738 | DOI Listing |
Arch Pharm (Weinheim)
January 2025
Department of Pharmacy, University of Salerno, Fisciano, Italy.
Inhibiting microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme involved in prostaglandin E (PGE) biosynthesis and tumor microenvironment (TME) homeostasis, is a valuable strategy for treating inflammation and cancer. In this work, 5-methylcarboxamidepyrrole-based molecules were designed and synthesized as new compounds targeting mPGES-1. Remarkably, compounds 1f, 2b, 2c, and 2d were able to significantly reduce the activity of the isolated enzyme, showing IC values in the low micromolar range.
View Article and Find Full Text PDFBiochem Res Int
October 2024
Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhanmodi, Dhaka 1205, Bangladesh.
The study investigates the antioxidant properties of , focusing on identifying its antioxidant compounds and chemical constituents. We compare antioxidant activities across its root, stem, flower, and leaf and examine the inhibition of reactive oxygen species (ROS)-generating enzymes by the plant's phytocompounds. We conducted a comprehensive analysis that included proximate analysis, mineral content assessment, and in vitro antioxidant characterization of various plant parts-root, stem, flower, and leaf.
View Article and Find Full Text PDFChem Biol Drug Des
October 2024
Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
J Agric Food Chem
October 2024
Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
The present study aimed to investigate the effects of ()-(-)-1-isothiocyanato-6-(methylsulfinyl)-hexane [()-6-HITC], the major isothiocyanate present in wasabi, in an model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. ()-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, ()-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects.
View Article and Find Full Text PDFJCI Insight
November 2024
Abramson Cancer Center, Perelman School of Medicine.
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