Naproxen-Derived New Compound Inhibits the NF-κB, MAPK and PI3K/Akt Signaling Pathways Synergistically with Resveratrol in RAW264.7 Cells
Yi Ou,
Zonglin You,
Min Yao,
Yingfan Cao,
Xiu Xue,
Min Chen,
Rihui Wu,
Lishe Gan,
Dongli Li,
Panpan Wu,
Xuetao Xu,
Wingleung Wong,
Vincent Kam Wai Wong,
Wenfeng Liu,
Jiming Ye,
Jingwei Jin
Affiliations
Yi Ou
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Zonglin You
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Min Yao
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Yingfan Cao
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Xiu Xue
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Min Chen
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Rihui Wu
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Lishe Gan
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Dongli Li
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Panpan Wu
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Xuetao Xu
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Wingleung Wong
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Vincent Kam Wai Wong
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
Wenfeng Liu
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Jiming Ye
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
Jingwei Jin
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
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.
