Abstract

The aim of the present in vitro study was carried out to evaluate the anti-inflammatory activity of Hypericum triquetrifolium extracts (HT-extract) on lipopolyssacharide -stimulated human monocytic (THP-1) cells and human peripheral blood mononuclear cells (PBMNCs). The expression and production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as the anti-inflammatory cytokine interleukin 10 (IL-10) were evaluated by assessing the levels of proteins and mRNA’s of TNF-α, IL-6 and IL-10 in both cell types. Cells were exposed to 5 μg lipopolyssacharide (LPS) /ml in the absence and presence of increasing concentrations of 50% ethanol extracts from the aerial parts of Hypericum triquetrifolium. The anti-inflammatory efficacy experiments were performed with HT-extract concentrations up to 250 μg/ml that had no cytotoxic effects as assessed with MTT and LDH assays. HT-extract remarkably inhibited the expression and secretion of TNF-α and IL-6 at a concentration of 250 μg/ml. HT-extract remarkably elevated IL-10 secretion and mRNA levels at 125 μg/ml. Furthermore, HT-extract exhibited relatively high antioxidant activity (IC50 of 5 μg/ml) as measured with DPPH assay. These findings indicate that HT-extract probably exerts anti-inflammatory effects at both protein and gene expression levels of the anti-inflammatory as well of the pro-inflammatory cytokines in PBMNCs.

Highlights

  • The Inflammation is a physiological response that is essential for eradicating pathogens. It is mediated by pro-inflammatory mediators, such as interleukin-1 (IL-1), the tumor necrosis factor alpha (TNF-α), gamma-interferon (IFN-γ), IL-12, and IL-18, and is suppressed by antiinflammatory mediators, such as IL-4, interleukin 10 (IL-10), and the transforming growth factor (TGF-β) [1,2,3]

  • Based on traditional Greco-Arab herbal medicine and on recent in vitro and in vivo reports in which HT-extract exhibited antiinflammatory effects by reducing the expression of pro-inflammatory cytokines and nitric oxide production [15,17], this study explored the anti-inflammatory mechanism of Hypericum triquetrifolium

  • Our results indicate that Hypericum triquetrifolium could modulate the regulatory mechanism of pro-inflammatory cytokines (TNF-α and interleukin 6 (IL-6)) as well as the anti-inflammatory cytokine (IL-10) in the LPSactivated THP-1 cells and in primary human peripheral blood mononuclear cells (PBMNCs)

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Summary

Introduction

The Inflammation is a physiological response that is essential for eradicating pathogens. It is mediated by pro-inflammatory mediators, such as interleukin-1 (IL-1), the tumor necrosis factor alpha (TNF-α), gamma-interferon (IFN-γ), IL-12, and IL-18, and is suppressed by antiinflammatory mediators, such as IL-4, IL-10, and the transforming growth factor (TGF-β) [1,2,3]. A “balance” between the production levels of the two types of cytokines is thought to determine the outcome of an inflammatory disease. Numerous in vitro studies showed that IL10 inhibits the production of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by LPS-activated macrophages [4,5]. Inhibitors of the pro-inflammatory cytokines (e.g., IL-1, IL-6 and TNF-α) have been considered as potential candidates for the development of antiinflammatory drugs [3,4,5,6,7,8]

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