Abstract
Abstract The naturally occurring stilbenoid oxyresveratrol was shown to influence inflammatory and metabolic processes. During cellular immune activation, tryptophan breakdown and neopterin formation via the enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and GTP-cyclohydrolase, respectively, are induced. Neopterin and the kynurenine to tryptophan ratio are reliable and pertinent biomarkers of Th1-type immune response and are also used in vitro to monitor effects of active plant ingredients on peripheral blood mononuclear cells (PBMCs). We investigated the effects of oxyresveratrol on the activity of the above-mentioned pathways in mitogen-stimulated human PBMC and in the myelomonocytic cell line THP-1. Oxyresveratrol exerted suppressive effects on tryptophan breakdown in both stimulated cell models. Of note, in PBMC, tryptophan breakdown was induced at lower concentrations (5–20 µM) and suppressed at higher treatment concentrations only. Neopterin formation was decreased dose-dependently in stimulated PBMC. In unstimulated PBMC similar, albeit lesser effects were observed. Data indicate that oxyresveratrol exerts distinct and concentration-dependent effects on different immune cell types. IDO-1 is targeted by oxyresveratrol and its activity can be modulated in both directions. Detailed investigations of the interactions would be interesting to fully explore the activity of this phytocompound.
Highlights
Oxyresveratrol is a polyphenolic phytoalexin produced by many plants of which some prominent examples are Morus alba L. (Moraceae) – known as white mulberry, jackfruit, Veratrum nigrum L. (Melanthiaceae), and Smilax china L. (Smilacaceae) [1,2]
Reports point toward interesting biological effects bearing diverse therapeutic potentials including the interference with different inflammatory signaling cascades, among those the inhibition of inducible nitric oxide synthase, the blocking of mitogen-activated protein kinase (MAPK), and NF-κB signaling pathways in murine macrophages are relevant to this study [6,7]
peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of healthy donors from whom informed consent was obtained that their donated blood might be used for scientific purposes in the case when it was not selected for transfusion
Summary
Oxyresveratrol is a polyphenolic phytoalexin produced by many plants of which some prominent examples are Morus alba L. (Moraceae) – known as white mulberry, jackfruit, Veratrum nigrum L. (Melanthiaceae), and Smilax china L. (Smilacaceae) [1,2]. Oxyresveratrol is a polyphenolic phytoalexin produced by many plants of which some prominent examples are Morus alba L. Oxyresveratrol is a stilbene related to resveratrol, which has been demonstrated to have multiple bioactivities and has been extensively studied (Figure 1) [3,4]. Protocols for the purification of oxyresveratrol from plant material as well as for the qualitative and quantitative analyses are available [5]. Fewer studies are available on the biological effects of oxyresveratrol. Reports point toward interesting biological effects bearing diverse therapeutic potentials including the interference with different inflammatory signaling cascades, among those the inhibition of inducible nitric oxide synthase (iNOS), the blocking of mitogen-activated protein kinase (MAPK), and NF-κB signaling pathways in murine macrophages are relevant to this study [6,7]. Oxyresveratrol has attracted renewed attention as a drug candidate as there
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