PMID- 27686451 OWN - NLM STAT- MEDLINE DCOM- 20170206 LR - 20181113 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 422 IP - 1-2 DP - 2016 Nov TI - Dihydromyricetin suppresses TNF-alpha-induced NF-kappaB activation and target gene expression. PG - 11-20 AB - Nuclear factor-kappa B (NF-kappaB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-kappaB 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-kappaB activation in TNF-alpha-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-kappaB alpha (IkappaBalpha), 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-alpha-induced apoptosis through suppressing the activation of NF-kappaB. In conclusion, our data indicate that dihydromyricetin may be a potentially useful therapeutic agent for inflammatory diseases. FAU - Tang, Nina AU - Tang N AD - 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. FAU - Ma, Juan AU - Ma J AD - 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. FAU - Wang, Ke Si AU - Wang KS AD - 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. FAU - Mi, Chunliu AU - Mi C AD - 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. FAU - Lv, Ying AU - Lv Y AD - 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. FAU - Piao, Lian Xun AU - Piao LX AD - 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. FAU - Xu, Guang Hua AU - Xu GH AD - 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. FAU - Li, Xuezheng AU - Li X AD - 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. FAU - Lee, Jung Joon AU - Lee JJ AD - 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. FAU - Jin, Xuejun AU - Jin X AD - 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. xjjin@ybu.edu.cn. LA - eng PT - Journal Article DEP - 20160929 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (AGFG1 protein, human) RN - 0 (Flavonols) RN - 0 (Nuclear Pore Complex Proteins) RN - 0 (RELA protein, human) RN - 0 (RNA-Binding Proteins) RN - 0 (TNF Receptor-Associated Factor 2) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - KD8QND6427 (dihydromyricetin) SB - IM MH - Active Transport, Cell Nucleus/drug effects MH - Apoptosis/*drug effects MH - Cell Nucleus/*metabolism MH - Flavonols/*pharmacology MH - Gene Expression Regulation/*drug effects MH - HeLa Cells MH - Humans MH - I-kappa B Kinase/metabolism MH - Nuclear Pore Complex Proteins/metabolism MH - RNA-Binding Proteins/metabolism MH - TNF Receptor-Associated Factor 2/metabolism MH - Transcription Factor RelA/*metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology OTO - NOTNLM OT - Apoptosis OT - Dihydromyricetin OT - Inflammation OT - IkappaBalpha OT - NF-kappaB EDAT- 2016/10/01 06:00 MHDA- 2017/02/07 06:00 CRDT- 2016/10/01 06:00 PHST- 2016/03/16 00:00 [received] PHST- 2016/08/17 00:00 [accepted] PHST- 2016/10/01 06:00 [pubmed] PHST- 2017/02/07 06:00 [medline] PHST- 2016/10/01 06:00 [entrez] AID - 10.1007/s11010-016-2799-6 [pii] AID - 10.1007/s11010-016-2799-6 [doi] PST - ppublish SO - Mol Cell Biochem. 2016 Nov;422(1-2):11-20. doi: 10.1007/s11010-016-2799-6. Epub 2016 Sep 29.