Kim, Bo-SungShin, MinwookKim, Kyu-WonHa, Ki-TaeBae, Sung-Jin2023-12-182023-12-182022-08-31Kim BS, Shin M, Kim KW, Ha KT, Bae SJ. NRF2 activation by 2-methoxycinnamaldehyde attenuates inflammatory responses in macrophages via enhancing autophagy flux. BMB Rep. 2022 Aug;55(8):407-412. doi: 10.5483/BMBRep.2022.55.8.065. PMID: 35725014; PMCID: PMC9442350.1976-670X35725014https://hdl.handle.net/20.500.14038/52876A well-controlled inflammatory response is crucial for the recovery from injury and maintenance of tissue homeostasis. The anti-inflammatory response of 2-methoxycinnamaldehyde (2-MCA), a natural compound derived from cinnamon, has been studied; however, the underlying mechanism on macrophage has not been fully elucidated. In this study, LPS-stimulated production of TNF-α and NO was reduced by 2-MCA in macrophages. 2-MCA significantly activated the NRF2 pathway, and expression levels of autophagy-associated proteins in macrophages, including LC3 and P62, were enhanced via NRF2 activation regardless of LPS treatment, suggesting the occurrence of 2-MCA-mediated autophagy. Moreover, evaluation of autophagy flux using luciferase-conjugated LC3 revealed that incremental LC3 and P62 levels are coupled to enhanced autophagy flux. Finally, reduced expression levels of TNF-α and NOS2 by 2-MCA were reversed by autophagy inhibitors, such as bafilomycin A1 and NH4Cl, in LPS-stimulated macrophages. In conclusion, 2-MCA enhances autophagy flux in macrophages via NRF2 activation and consequently reduces LPS-induced inflammation. [BMB Reports 2022; 55(8): 407-412].enCopyright © 2022 by the The Korean Society for Biochemistry and Molecular Biology. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.; Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/2-MethoxycinnamaldehydeAutophagyInflammationLPSNRF2Journal ArticleBMB reports