Methyl 3,4,5-trimethoxycinnamate suppresses inflammation in RAW264.7 macrophages and blocks macrophage –adipocyte interaction

AbstractMethyl 3,4,5-trimethoxycinnamate (MTC) is a bioactive natural phenylpropanoid. We evaluated anti-inflammatory effects of synthetic MTC in RAW264.7 macrophages and RAW264.7 –3T3-L1 adipocytes co-culture. Levels of cytokines and chemokines, as well as NO and PGE2 in cell supernatants  were analysed using ELISAs, Griess assay and enzyme immunoassays, respectively. In-cell cytoblot was used to assess levels of proteins; while DNA binding and reporter gene assays were used to measure transcription factor DNA binding and transcriptional activities, respectively. Glucose uptake in a dipocytes was evaluated with 2‐deoxy‐2‐[(7‐nitro‐2, 1, 3‐benzoxadiazol‐4‐yl) amino]‐d‐glucose uptake. MTC (5–20 µM) suppressed LPS + IFNγ-induced release of TNFα, IL-6 and IL-1β, as well as NO/iNOS and PGE2/COX-2 levels in RAW264.7 cells. Furthermore, there was a reduction in phospho-I κB and phospho-p65 proteins, accompanied by a reduction in total IκB in RAW264.7 cells. Further studies showed that MTC also produced a reduction in NF-κB DNA binding and luciferase activity. Treatment of RAW264.7 cells with MTC (5–20 µM) resulted in enhanced DNA binding of Nrf2 and an increa se in ARE-luciferase activity. In a macrophage–adipocyte co-culture, the compound reduced the release of TNFα, IL-6, IL-1β, MCP-1 and RANTES, while enhancing glucose uptake and activation of AMPKα. Our results suggest that MTC produced anti-inflammatory and antioxidant activities i...
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research