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 $ PGE_{2} $ 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 + IFNγ-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-IκB 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 increase 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 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..

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:28

Enthalten in:

Inflammopharmacology - 28(2020), 5 vom: 16. Mai, Seite 1315-1326

Sprache:

Englisch

Beteiligte Personen:

Olajide, Olumayokun A. [VerfasserIn]
Akande, Idowu S. [VerfasserIn]
da Silva Maia Bezerra Filho, Carlos [VerfasserIn]
Lepiarz-Raba, Izabela [VerfasserIn]
de Sousa, Damião Pergentino [VerfasserIn]

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Volltext [kostenfrei]

Themen:

3T3-L1 adipocytes
Anti-inflammatory
Methyl 3,4,5-trimethoxycinnamate
NF-κB
Natural product
RAW264.7 macrophages

Anmerkungen:

© The Author(s) 2020

doi:

10.1007/s10787-020-00720-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2119712557

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