Peucedanum ostruthium Inhibits E-Selectin and VCAM-1 Expression in Endothelial Cells through Interference with NF-κB Signaling

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.

Pterocarpus santalinus Selectively Inhibits a Subset of Pro-Inflammatory Genes in Interleukin-1 Stimulated Endothelial Cells

“…In previous studies, we have analyzed the anti-inflammatory activity of twenty selected herbal extracts using the reduction of the IL-1 stimulated expression of the cell adhesion molecule E-selectin in human umbilical vein endothelial cells (HUVEC) as readout ( Lammel et al, 2020 ). Here, based on the strength and robustness of its inhibitory action, we have chosen PS for further in-depth analysis.…”

“…Both analyses confirmed the suppressive effect. Moreover, during the initial characterization of the extract, E-selectin protein levels have been assayed by cell ELISA and found to be down-regulated by PS ( Lammel et al, 2020 ).…”

“…Despite these studies, the underlying molecular mechanism(s) remain poorly understood. From a pre-characterized set of extracts of herbal and fungal origin, P. santalinus has caught our attention due to its strong and robust effect in a model of IL-1 stimulated EC ( Lammel et al, 2020 ). EC play a key role in the inflammatory response due to their control of immune cell transmigration, which requires the tightly regulated expression of cell adhesion molecules, interleukins, and chemotactic factors.…”

“…Since NF-κB is a prominent regulator of pro-inflammatory genes in EC and has been demonstrated to be a target of many natural products ( Kim et al, 2007 ; Seigner et al, 2019 ; Lammel et al, 2020 ), we reasoned that this transcription factor might also be affected by PS. A reporter gene analysis confirmed this hypothesis ( Figure 2A ), and was further substantiated by IκBα phosphorylation and degradation ( Figure 2B ).…”

Topical Collection “Pharmacology of Medicinal Plants”

“…Some of its major bioactive components need further investigation to evaluate their potential as drug candidates [ 10 ]. Lammel et al probed the potential to suppress the expression of the inflammatory markers shown by some natural remedies traditionally used against different inflammatory diseases, finding that among them the extract derived from the roots and rhizomes of Peucedanum ostruthium showed a pronounced and a dose-dependent inhibitory effect [ 11 ]. Leite et al studied the chemical composition of the pulp of the Brazilian Savanna fruit Dipteryx alata and evaluated its toxic effects, its influence on the life expectancy of the nematode Caenorhabditis elegans , and its antioxidant activities in vitro and in vivo, demonstrating its potential use as a functional and nutraceutical food [ 12 ].…”