Ethanolic Extract of Propolis and CAPE as Cardioprotective Agents against LPS and IFN-α Stressed Cardiovascular Injury

Abstract

The inflammatory process is triggered by several factors such as toxins, pathogens, and damaged cells, promoting inflammation in various systems, including the cardiovascular system, leading to heart failure. The link between periodontitis as a chronic inflammatory disease and cardiovascular disease is confirmed. Propolis and its major component, caffeic acid phenethyl ester (CAPE), exhibit protective mechanisms and anti-inflammatory effects on the cardiovascular system. The objective of the conducted study was to assess the anti-inflammatory effects of the Polish ethanolic extract of propolis (EEP) and its major component-CAPE-in interferon-alpha (IFN-α), lipopolysaccharide (LPS), LPS + IFN-α-induced human gingival fibroblasts (HGF-1). EEP and CAPE were used at 10-100 µg/mL. A multiplex assay was used for interleukin and adhesive molecule detection. Our results demonstrate that EEP, at a concentration of 25 µg/mL, decreases pro-inflammatory cytokine IL-6 in LPS-induced HGF-1. At the same concentration, EEP increases the level of anti-inflammatory cytokine IL-10 in LPS + IFN-α-induced HGF-1. In the case of CAPE, IL-6 in LPS and LPS + IFN-α induced HGF-1 was decreased in all concentrations. However, in the case of IL-10, CAPE causes the highest increase at 50 µg/mL in IFN-α induced HGF-1. Regarding the impact of EEP on adhesion molecules, there was a noticeable reduction of E-selectin by EEP at 25, 50, and100 µg/mL in IFN-α -induced HGF-1. In a range of 10-100 µg/mL, EEP decreased endothelin-1 (ET-1) during all stimulations. CAPE statistically significantly decreases the level of ET-1 at 25-100 µg/mL in IFN-α and LPS + IFN-α. In the case of intercellular adhesion molecule-1 (ICAM-1), EEP and CAPE downregulated its expression in a non-statistically significant manner. Based on the obtained results, EEP and CAPE may generate beneficial cardiovascular effects by influencing selected factors. EEP and CAPE exert an impact on cytokines in a dose-dependent manner.

Keywords: adhesion molecules; caffeic acid phenethyl ester; cytokines; inflammation; propolis.

Figure 1

The effect of EEP on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 1

The effect of EEP on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 1

The effect of EEP on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 1

The effect of EEP on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 1

The effect of EEP on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 2

The effect of CAPE on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 2

The effect of CAPE on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 2

The effect of CAPE on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 2

The effect of CAPE on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 2

The effect of CAPE on the secretion of selected interleukins and adhesion molecules in LPS, IFN-α, and LPS + IFN-α-induced HGF-1. * means p < 0.05.

Figure 3

Dendrogram obtained via the HCA analysis of data regarding the behavior of IL-6, IL-10, E-selectin, ET-1, and ICAM-1 secretion by HGF-1 fibroblasts stimulated by LPS, IFN-α, and LPS + IFN-α following treatment with EEP.

Figure 4

PCA score plot of obtained data based on the effect of EEP at different concentrations on IL-6, IL-10, E-selectin, ET-1, and ICAM-1 secretion by HGF-1 fibroblasts stimulated by LPS, IFN-α, and LPS + IFN-α.

Figure 5

Dendrogram obtained via the HCA analysis of data regarding the behavior of IL-6, IL-10, E-selectin, ET-1, and ICAM-1 secretion by HGF-1 fibroblasts stimulated by LPS, IFN-α, and LPS + IFN-α following treatment with CAPE.

Figure 6

PCA score plot of obtained data based on the effect of CAPE at different concentrations on IL-6, IL-10, E-selectin, ET-1, and ICAM-1 secretion by HGF-1 fibroblasts stimulated by LPS, IFN-α, and LPS + IFN-α.