Naproxen-Derived New Compound Inhibits the NF-κB, MAPK and PI3K/Akt Signaling Pathways Synergistically with Resveratrol in RAW264.7 Cells
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Published:2023-04-12
Issue:8
Volume:28
Page:3395
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Ou Yi1, You Zonglin1, Yao Min1, Cao Yingfan1, Xue Xiu1, Chen Min1, Wu Rihui12, Gan Lishe12, Li Dongli12ORCID, Wu Panpan12ORCID, Xu Xuetao12, Wong Wingleung12ORCID, Wong Vincent Kam Wai3, Liu Wenfeng12, Ye Jiming14, Jin Jingwei12ORCID
Affiliation:
1. School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China 2. International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China 3. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China 4. Lipid Biology and Metabolic Disease Research Group, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3000, Australia
Abstract
Naproxen is widely used for anti-inflammatory treatment but it can lead to serious side effects. To improve the anti-inflammatory activity and safety, a novel naproxen derivative containing cinnamic acid (NDC) was synthesized and used in combination with resveratrol. The results showed that the combination of NDC and resveratrol at different ratios have a synergistic anti-inflammatory efficacy in RAW264.7 macrophage cells. It was indicated that the combination of NDC and resveratrol at a ratio of 2:1 significantly inhibited the expression of carbon monoxide (NO), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and reactive oxygen species (ROS) without detectable side effects on cell viability. Further studies revealed that these anti-inflammatory effects were mediated by the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) signaling pathways, respectively. Taken together, these results highlighted the synergistic NDC and resveratrol anti-inflammatory activity that could be further explored as a strategy for the treatment of inflammatory disease with an improved safety profile.
Funder
National Natural Science Foundation of China Natural Science Foundation of Guangdong-Guangzhou Joint Fund Department of Education of Guangdong Province Basic and Theoretical Research Programs of Science and Technology Foundation of Jiangmen Joint Fund of Wuyi University-Macau
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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