Tang Nina, Ma Juan, Wang Ke Si, Mi Chunliu, Lv Ying, Piao Lian Xun, Xu Guang Hua, Li Xuezheng, Lee Jung Joon, Jin Xuejun
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
Mol Cell Biochem. 2016 Nov;422(1-2):11-20. doi: 10.1007/s11010-016-2799-6. Epub 2016 Sep 29.
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.
据报道，核因子-κB（NF-κB）在包括炎症、细胞凋亡和血管生成在内的许多生理过程中起关键作用。我们从传统草药显齿蛇葡萄中发现了一种有效的天然NF-κB抑制剂二氢杨梅素，该草药在食品和医药领域有着悠久的使用历史。在本研究中，我们证明了二氢杨梅素对TNF-α诱导的HeLa细胞中NF-κB激活的影响。发现二氢杨梅素能显著抑制NF-κBα抑制剂（IκBα）的磷酸化和降解，以及随后p65的核转位。二氢杨梅素还通过抑制衔接蛋白、TNF受体相关因子2（TRAF2）和受体相互作用蛋白1（RIP1）的表达，对IKK的上游信号产生影响。此外，目前的结果表明，二氢杨梅素通过抑制NF-κB的激活，导致参与炎症、增殖的靶基因下调，并增强TNF-α诱导的细胞凋亡。总之，我们的数据表明二氢杨梅素可能是一种潜在的治疗炎症性疾病的有用药物。
