Abstract
Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.
Highlights
With increasing attention on healthy diets, people are increasingly oriented to seek a better lifestyle that is comprised of correct behaviors in dietary choices
Treatment with PU at high concentrations (50 μM) significantly inhibited the levels of IL-6 and tumor necrosis factor (TNF)-α that were induced by LPS. These results indicated that PU exerts anti-inflammatory activity via the suppression of Nitric Oxide (NO) production and pro-inflammatory cytokines IL-6 and TNF-α in LPS-induced RAW264.7 cells
We found that PU attenuated LPS-induced phosphorylation of nuclear transcription factor κB (NF-κB), p38, JNK, and ERK mitogen-activated protein kinases (MAPKs), suggesting that PU suppressed NF-κB and MAPK signaling pathway to suppress the release of LPS-induced NO, TNF-α, and IL-6
Summary
With increasing attention on healthy diets, people are increasingly oriented to seek a better lifestyle that is comprised of correct behaviors in dietary choices. Dietary guidelines around the world are based on the daily consumption of plant foods rich in phytochemicals that are able to cure diseases and attain a general state of health [1]. Epidemiological and scientific studies have reported that a high intake of fruits and vegetables rich in polyphenolic phytochemicals protect against diabetes mellitus, cerebrovascular diseases, neurodegenerative diseases, and arthritis [2,3,4]. Pomegranate shows brilliant antioxidant [2], anticancer [3] and anti-inflammatory [4,5] properties attributed to its high ingredients of polyphenols including ellagitannins, ellagic acid, and other polyphenols [6,7]. Previous research has reported that punicalagin (PU), an ellagitannin that is the most abundant of these polyphenols, exhibits potent
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