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

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 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 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?+?IFN?-induced release of TNF?, IL-6 and IL-1?, as well as NO/iNOS and PGE2/COX-2 levels in RAW264.7 cells. Furthermore, there was a reduction in phospho-I?B and phospho-p65 proteins, accompanied by a reduction in total I?B in RAW264.7 cells. Further studies showed that MTC also produced a reduction in NF-?B 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 co-culture, the compound reduced the release of TNF?, IL-6, IL-1?, MCP-1 and RANTES, while enhancing glucose uptake and activation of AMPK?. 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.

SUBMITTER: Olajide OA

PROVIDER: S-EPMC7524821 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Olajide Olumayokun A OA Akande Idowu S IS da Silva Maia Bezerra Filho Carlos C Lepiarz-Raba Izabela I de Sousa Damião Pergentino DP

Inflammopharmacology 20200516 5

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<sub>2</sub> 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 transcr ...[more]

PMID: 32418005

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

Publications

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

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