Abstract
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.
Highlights
The inflammatory reaction is a common feature of several diseases, including cardiovascular, gastrointestinal, and neurodegenerative, as well as joint and skin disorders
Natural materials from 17 plant species and three polypore species have been selected based on several criteria, primarily because of their long-standing traditional use in the field of inflammation and related areas, as well as anti-inflammatory effects described in the literature without in depth knowledge of their molecular mechanisms
Besides the 17 traditional herbal drugs, three polypore species were selected for the preparation of extracts, since they have been extensively used in Traditional Chinese Medicine (TCM) for the treatment of various ailments, and for their health-promoting effects around the world [22]
Summary
The inflammatory reaction is a common feature of several diseases, including cardiovascular, gastrointestinal, and neurodegenerative, as well as joint and skin disorders Inflammatory mediators such as IL-1 and TNF or bacterial LPS evoke the expression of a complex set of genes in the endothelium that encode, e.g., chemoattractants and adhesion molecules, a pre-requisite for the adherence and transmigration of immune cells through the vascular wall into the underlying tissue, where they migrate towards the site of injury. Examples of induced genes include the adhesion molecules E-selectin, ICAM-1, VCAM-1, the cytokines IL-1, IL-6, IL-8, chemokines and their receptors, cyclooxygenase, and anti-apoptotic proteins of the IAP family and A20. NF-κB comprises a family of five members that can form homoBiomolecules 2020, 10, 1215; doi:10.3390/biom10091215 www.mdpi.com/journal/biomolecules
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