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

Olumayokun Olajide, Idowu Akande, Carlos da Silva Maia Bezerra Filho, Izabela Lepiarz-Raba, Damião Pergentino de Sousa

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Abstract

Methyl 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 PGE 2 in cell supernatants. 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 adipocytes was evaluated with 2‐deoxy‐2‐[(7‐nitro‐2, 1, 3‐benzoxadiazol‐4‐yl) amino]‐D‐glucose uptake. MTC (5-20 μM) suppressed LPS + IFNg-induced release of TNFα, IL-6 and IL-1β, as well as NO/iNOS and PGE 2 /COX-2 levels in RAW264.7 cells. Furthermore, there was a reduction in phospho-IkB and phospho-p65 proteins, accompanied by a reduction in total IkB in RAW264.7 cells. Further studies showed that MTC also produced a reduction in NF-kB DNA binding and luciferase activity. Treatment of RAW264.7 cells with MTC (5-20 μM) resulted in enhanced DNA binding of Nrf2 and an increase in ARE luciferase activity. In a macrophage-adipocyte coculture, 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 in macrophages. MTC also prevented inflammation in macrophage-adipocyte co-culture. The effect of MTC on glucose uptake in adipocytes is proposed to be linked to activation of AMPK.
Original languageEnglish
JournalInflammopharmacology
Publication statusAccepted/In press - 30 Apr 2020

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Olajide, O., Akande, I., da Silva Maia Bezerra Filho, C., Lepiarz-Raba, I., & de Sousa, D. P. (Accepted/In press). Methyl 3, 4, 5-trimethoxycinnamate suppresses inflammation in RAW264.7 macrophages and blocks macrophage-adipocyte interaction. Inflammopharmacology.