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. 2020 Feb 17;20(1):56.
doi: 10.1186/s12906-020-2844-6.

Ficus Deltoidea Suppresses Endothelial Activation, Inflammation, Monocytes Adhesion and Oxidative Stress via NF-κB and eNOS Pathways in Stimulated Human Coronary Artery Endothelial Cells

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Free PMC article

Ficus Deltoidea Suppresses Endothelial Activation, Inflammation, Monocytes Adhesion and Oxidative Stress via NF-κB and eNOS Pathways in Stimulated Human Coronary Artery Endothelial Cells

Amirah Mohd Ariff et al. BMC Complement Med Ther. .
Free PMC article

Abstract

Background: Ficus deltoidea (FD) has been shown to have antidiabetic, anti-inflammatory, antinociceptive and antioxidant properties. However, its effects on key events in the pathogenesis of atherosclerosis are unknown.

Aim: To investigate the endothelial activation, inflammation, monocyte-endothelial cell binding and oxidative stress effects of four FD varieties.

Methods: Human coronary artery endothelial cells (HCAEC) were incubated with different concentrations of aqueous ethanolic extracts of FD var. trengganuensis (FDT), var. kunstleri (FDK), var. deltoidea (FDD) and var. intermedia (FDI), together with LPS. Protein and gene expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), interleukin-6 (IL-6), Nuclear factor-κB (NF-κB) p50 and p65 and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. Adhesion of monocyte to HCAEC and formation of reactive oxygen species (ROS) were detected by Rose Bengal staining and 2'-7'-dichlorofluorescein diacetate (DCFH-DA) assay.

Results: FDK exhibited the highest inhibition of biomarkers in relation to endothelial activation and inflammation, second in reducing monocyte binding (17.3%) compared to other varieties. FDK (25.6%) was also the most potent at decreasing ROS production.

Conclusion: FD has anti-atherogenic effects, possibly mediated by NF-κB and eNOS pathways; with FDK being the most potent variety. It is potentially beneficial in mitigating atherogenesis.

Keywords: Atherosclerosis; Endothelial activation; Ficus deltoidea; Inflammation; Monocyte adhesion; Oxidative stress.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Cytotoxic effects of FDT, FDK, FDD and FDI on of HCAEC and RAW 264.7 cells. The viability of (a) HCAEC is good until FD concentration of 40 μg/ml; whilst (b) RAW 264.7 remains good at 500 μg/ml. Results are presented as percentage (%) of controls (untreated cells). Data are expressed as mean ± SD (n = 3). Abbreviation: FDT (FD var. trengganuensis), FDK (FD var. kunstleri), FDD (FD var. deltoidea), FDI (FD var. intermedia)
Fig. 2
Fig. 2
Effects of FD extracts on a) VCAM-1, b) ICAM-1, c) E-selectin, d) IL-6 protein expression in LPS-stimulated HCAEC. Before incubation, protein expression in the media was measured by ELISA. Data are expressed as mean ± SD (n = 3). Statistical analysis: ANOVA, post-hoc with Bonferroni correction; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to HCAEC incubated with LPS alone. Abbreviation: UNT (untreated), LPS (lipopolysaccharide), FDT (FD var. trengganuensis), FDK (FD var. kunstleri), FDD (FD var. deltoidea), FDI (FD var. intermedia)
Fig. 3
Fig. 3
Effects of FD on a) VCAM-1, b) ICAM-1, c) E-selectin, d) IL-6 gene expression in LPS-stimulated HCAEC cell pellets. Data are expressed as mean ± SD (n = 3). Statistical analysis: ANOVA, post-hoc with Bonferroni correction; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to HCAEC incubated with LPS alone. Abbreviation: LPS (lipopolysaccharide), FDT (FD var. trengganuensis), FDK (FD var. kunstleri), FDD (FD var. deltoidea), FDI (FD var. intermedia)
Fig. 4
Fig. 4
Effects of FD on a) NF-κB p50 in nuclear lysate protein expression, b) NF-κB p50 in cytoplasmic lysate protein expression, c) NF-κB p65 in nuclear lysate protein expression, d) NF-κB p65 in cytoplasmic lysate protein expression, e) NF-κB p50 gene expression in cell pellets, f) NF-κB p65 gene expression in cell pellets, g) eNOS protein expression in cell lysate, and h) eNOS gene expression in cell pellets in LPS-stimulated HCAEC. Data are expressed as mean ± SD (n = 3). Statistical analysis: ANOVA, post-hoc with Bonferroni correction; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to HCAEC incubated with LPS alone. Abbreviation: UNT (untreated), LPS (lipopolysaccharide), FDT (FD var. trengganuensis), FDK (FD var. kunstleri), FDD (FD var. deltoidea), FDI (FD var. intermedia)
Fig. 5
Fig. 5
Effects of FD extracts (5–40 μg/ml) on the monocyte-endothelial cell binding assay. Data expressed as mean ± SD. Statistical analysis: ANOVA, post-hoc with Bonferroni correction; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to HCAEC incubated with LPS alone. Abbreviation: UNT (untreated), LPS (lipopolysaccharide), FDT (FD var. trengganuensis), FDK (FD var. kunstleri), FDD (FD var. deltoidea), FDI (FD var. intermedia)
Fig. 6
Fig. 6
Effects of different concentrations of FD varieties (15.625–500 μg/ml) on the percentage increase of DCF fluorescence in RAW 264.7 cells stimulated with LPS and IFN-γ. Results are expressed as a percentage (%) of fluorescence intensity. Data are expressed as mean ± SD (n = 3). Statistical analysis: ANOVA, post-hoc with Bonferroni correction; **p < 0.01 and ***p < 0.001 compared to HCAEC incubated with LPS alone. Abbreviation: UNT (untreated), LPS (lipopolysaccharide), IFN-γ (interferon gamma), Q (Quercetin), FDT (FD var. trengganuensis), FDK (FD var. kunstleri), FDD (FD var. deltoidea), FDI (FD var. intermedia)

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