Abstract
Nuclear factor-kappa B (NF-κB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-κB inhibitor, dihydromyricetin, from the traditional herb Ampelopsis grossedentata, which has a long history of use in food and medicine. In this study, we demonstrated the effect of dihydromyricetin on NF-κB activation in TNF-α-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent nuclear translocation of p65. Dihydromyricetin also has an impact on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2), and receptor-interacting protein 1 (RIP1). Furthermore, the current results reveal that dihydromyricetin led to the downregulation of target genes involved in inflammation, proliferation, as well as potentiation of TNF-α-induced apoptosis through suppressing the activation of NF-κB. In conclusion, our data indicate that dihydromyricetin may be a potentially useful therapeutic agent for inflammatory diseases.
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Abbreviations
- NF-κB:
-
Nuclear factor-κB
- IκBα:
-
Inhibitor of NF-κB alpha
- IKK:
-
IκB kinase
- TRAF2:
-
TNF receptor-associated factor 2
- RIP1:
-
Receptor-interacting protein 1
- Topo-I:
-
Topoisomerase-I
- TNF-α:
-
Tumor necrosis factor alpha
- MMP-9:
-
Matrix metalloproteinase-9
- iNOS:
-
Inducible nitric oxide synthase
- c-IAP2:
-
Cellular inhibitor of apoptosis-2
- Bcl-2:
-
B-cell lymphoma 2
- COX-2:
-
Cyclooxygenase-2
- ICAM-1:
-
Inter-cellular adhesion molecule-1
- VEGF:
-
Vascular endothelial growth factor
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Acknowledgments
This work was partially supported by the National Natural Science Foundation of China, No. 81360496. This study also received assistance from Jilin Province Science and Technology Development Plan item (20150101229JC) and Project of Education Department of Jilin Province 2016 (281).
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Tang, N., Ma, J., Wang, K.S. et al. Dihydromyricetin suppresses TNF-α-induced NF-κB activation and target gene expression. Mol Cell Biochem 422, 11–20 (2016). https://doi.org/10.1007/s11010-016-2799-6
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DOI: https://doi.org/10.1007/s11010-016-2799-6