Immunomodulatory Effect of Raspberry (Rubus idaeus L.) Fruit Extracts on Activated Macrophages and Dysfunctional Vascular Endothelial Cells

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Abstract
Background: Growing evidence emphasizes the beneficial effect of flavonoids such as anthocyanins as key constituents in lowering cardiovascular risk, and incorporating daily anthocyanin-rich fruits into the diet significantly impacts public health. Methods: The effect of raspberry fruit bioactive polyphenols on the molecular pathways in inflammation was analyzed in activated RAW 264.7 macrophages, and protective potential against endothelial dysfunction was evaluated using TNF-α-induced human umbilical vein endothelial cells (HUVECs). Results: The results have shown that raspberry fruit (RBF) extract, as well as anthocyanin and polyphenol fractions, exhibited a potent anti-inflammatory effect in macrophage cell culture by inhibition of LPS-elicited induction of pro-inflammatory gene expressions such as IL-6, IL-1β, TNF-α, and NF-κB. Moreover, RBF and both fractions have shown protective effect on endothelial functions by decreasing the expression of several inflammation-related genes and adhesion molecules such as IL-6, IL-1b, VCAM-1, ICAM-1, and SELE in TNF-α-induced HUVECs. Conclusions: Consumption of raspberry fruit and/or polyphenol-rich extract can help prevent the development of early atherosclerosis. The underlying mechanisms are related to improved inflammation status and vascular endothelial function. Due to raspberries' strong anti-inflammatory properties, incorporating them into the daily diet may significantly lower the risk of inflammation-related non-communicable diseases.
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