Dihydromyricetin suppresses TNF-α-induced NF-κB activation and target gene expression

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.

Anti-inflammatory effects of dihydromyricetin in a mouse model of asthma

“…In addition, when NF-κB is activated, several inflammatory cytokines are upregulated in asthmatic airways, and the AHR and mucus secretion are enhanced in allergic inflammation (41). Previous studies have suggested that DHM inhibits the activation of NF-κB and the phosphorylation of p38 and c-Jun N-terminal kinase, but not ERK1/2, in lipopolysaccharide-stimulated macrophages (18,20,42). In the present study, it was hypothesized that DHM inhibited the inflammatory response in the asthma model through a similar mechanism; however, this requires clarification in future investigations.…”

Dihydromyricetin Protects against Bone Loss in Ovariectomized Mice by Suppressing Osteoclast Activity

“…The classical NF-κB pathway plays an important role in osteoclast formation, differentiation, and bone-resorbing activity, and RANKL-RANK signaling is indispensable for osteoclastogenesis by activation of downstream pathways, including NF-κB and MAPK ( Soysa et al, 2009 ). Studies also show that DMY exerts its anti-inflammatory action through suppressing the activation of NF-κB and MAPK signaling pathways ( Hou et al, 2015 ; Tang et al, 2016 ). This hints that NF-κB may be the pathway by which DMY suppresses osteoclastogenesis, as our results suggest DMY inhibits multiple downstream pathways of RANK signaling including NF-κB and the phosphorylation of ERK and JNK.…”

“…Recent studies have demonstrated that DMY suppresses the levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in lipopolysaccharide-treated mice. DMY exerts its anti-inflammatory action by suppressing the activation of NF-κB and the phosphorylation of p38 and JNK, and it may be a potentially useful therapeutic agent for inflammatory-related diseases ( Hou et al, 2015 ; Tang et al, 2016 ). Since NF-κB pathways are essential for osteoclastogenesis ( Boyle et al, 2003 ), we propose that there is an impact of DMY in osteoclastogenesis.…”

The Versatile Effects of Dihydromyricetin in Health

“…Specifically, dihydromyricetin dephosphorylates and inhibits the degradation of I κ B α , inactivates p65 nuclear translocation and downregulates the TNF- α -induced expression of TRAF2 and RIP1. In addition, dihydromyricetin also downregulates the expression of NF- κ B target genes, including c-IAP2, Bcl-2, TRAF1, iNOS, cyclin D1, COX-2, ICAM-1, MMP-9, and VEGF [ 21 ] ( Table 1 ). In asthmatic mouse model, ovalbumin promotes the secretion of proinflammatory cytokines, IgE, and IgG1 and the infiltration of inflammatory cells into the bronchoalveolar lavage.…”