Ellagic Acid Suppresses ApoB Secretion and Enhances ApoA-1 Secretion from Human Hepatoma Cells, HepG2

Abstract

The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.

Ferroportin-dependent ferroptosis induced by ellagic acid retards liver fibrosis by impairing the SNARE complexes formation

“…Moreover, EA treatment could not further increase the CCl 4 -induced cell apoptosis, clearly illustrating that EA enhanced the death of activated HSCs via the ferroptotic pathway rather than the apoptosis pathway. Interestingly, EA-induced HSC ferroptosis has a selective effect; EA neither inhibited growth nor induced ferroptotic events in both primary hepatocytes and human HepG2 cells in normal condition or under injury condition, which is consistent with previous findings that no growth inhibition was observed when hepatocytes and HepG2 cells were treated with 50 μM EA [ 43 , 44 ], suggesting that EA has a selective effect on ferroptosis induction.…”

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease

“…Based on T-distributed stochastic neighbor embedding (t-SNE) analysis and differentially expressed gene analysis, we annotated three nonimmune populations and seven immune cell populations. Nonimmune cell types primarily consisted of three hepatocyte subclusters: Hepatocyte (Hep) 1 expressing aqp12 ( 27 ) and itih2 ( 28 ), Hep 2 expressing ahsg1 ( 29 ), apoa1a ( 30 ) and apoa4b . 1 ( 31 ), and Hep3 expressing msmo1 ( 23 ) and hmgcs1 ( 23 ).…”

Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…The mentioned trials showed reductions on total cholesterol and LDL-c. It has been reported the effect of EA upregulating the expression of the LDL-c receptor increasing the LDL-c uptake [ 16 ], and its effect increasing the secretion of the apolipoprotein apoA-1 (major apolipoprotein HDL-c), inhibition of apolipoprotein B (component of LDL-c and VLDL) [ 15 ], and gen-level suppressor action of EA on the microsomal triacylglycerol transfer protein [ 16 ] that mobilizes triglycerides to ApoB. Despite these reported effects, in our study, total cholesterol and LDL-c showed no significant reductions.…”

“…Similar outcomes from an in vitro study were reported by Wang et al [ 14 ], who found that EA inhibited adipogenesis through the suppression of adipocytes differentiation, interrupting the cell cycle [ 14 ]. It has been observed that the consumption of EA improves plasma lipid levels through various mechanisms [ 8 ], like increasing the secretion of apolipoprotein apoA-1, the main apolipoprotein of the high-density lipoprotein cholesterol (HDL-c); and by inhibiting apolipoprotein B, a component of low-density lipoprotein cholesterol (LDL-c) and very low-density lipoprotein (VLDL) [ 15 ]. EA also upregulates the expression of the LDL-c receptor, via the ERK signaling pathway, increasing the LDL-c uptake [ 16 ].…”