Twenty natural remedies traditionally used against different inflammatory diseases were probed for their potential to suppress the expression of the inflammatory markers E-selectin and VCAM-1 in a model system of IL-1 stimulated human umbilical vein endothelial cells (HUVEC). One third of the tested extracts showed in vitro inhibitory effects comparable to the positive control oxozeaenol, an inhibitor of TAK1. Among them, the extract derived from the roots and rhizomes of Peucedanum ostruthium (i.e., Radix Imperatoriae), also known as masterwort, showed a pronounced and dose-dependent inhibitory effect. Reporter gene analysis demonstrated that inhibition takes place on the transcriptional level and involves the transcription factor NF-κB. A more detailed analysis revealed that the P. ostruthium extract (PO) affected the phosphorylation, degradation, and resynthesis of IκBα, the activation of IKKs, and the nuclear translocation of the NF-κB subunit RelA. Strikingly, early effects on this pathway were less affected as compared to later ones, suggesting that PO may act on mechanism(s) that are downstream of nuclear translocation. As the majority of cognate NF-κB inhibitors affect upstream events such as IKK2, these findings could indicate the existence of targetable signaling events at later stages of NF-κB activation.
Biomolecules (2020-08-23)
Christoph Lammel, Julia Zwirchmayr, Jaqueline Seigner, Judith M Rollinger, Rainer de Martin
PMID32825714
摘要
材料
产品编号
品牌
产品描述
Sigma-Aldrich
L -谷氨酰胺 溶液, 200 mM, solution, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
(5Z)-7-Oxozeaenol, 来源于弯孢菌属, (5Z)-7-Oxozeaenol, CAS 66018-38-0, is a cell-permeable, highly potent, selective, irreversible, and ATP-competitive inhibitor of MAPKKK TAK1 activity (IC50 = 8 nM).