Ginsenosides from Korean red ginseng modulate T cell function via the regulation of NF-AT-mediated IL-2 production

Food Science and Biotechnology - Korean red ginseng is a traditional health food frequently used to prevent or treat various diseases worldwide. In this study, we evaluated the immunomodulatory...     

Korean red ginseng extract alleviates atherosclerotic lesions in apolipoprotein E knockout mice

This study was to evaluate the anti-atherosclerotic effect of Korean red ginseng (KRG) in apolipoprotein E knockout (ApoE KO) mice. Female ApoE KO mice were divided into 2 groups and were treated via intragastric inoculation for 21 weeks. The body weight increased gradually in both the KRG extract inoculation group and the control group inoculated with saline. Plaque lesion areas in the aortic sinus were reduced largely in the KRG inoculation group than in the control group. Triglyceride and inflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) were significantly reduced in the KRG inoculation group. Additionally, the KRG inoculation group showed significantly lower cardiovascular inflammation by ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography compared to that in the control group. Taken together, KRG alleviates atherosclerotic lesions through MCP-1 and TNF-α suppression. These results suggest that KRG could be a valuable therapeutic strategy for the treatment of atherosclerosis.     

Phillyrin attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/AMP-activated protein kinase-dependent signalling

Phillyrin, an active constituent found in many medicinal plants and certain functional foods, has anti-obesity activity in vivo. The aim of our study was to provide new data on the molecular mechanism(s) underlying the role of phillyrin in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes. We found that phillyrin suppressed high glucose-induced lipid accumulation in HepG2 cells. Phillyrin strongly inhibited high glucose-induced fatty acid synthase (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. Moreover, use of the pharmacological AMP-activated protein kinase (AMPK) inhibitor compound C revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells. Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the phillyrin-enhanced activation of AMPK in HepG2 hepatocytes. These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.     

Mulberry extract inhibits oleic acid-induced lipid accumulation via reduction of lipogenesis and promotion of hepatic lipid clearance

BACKGROUND: Mulberries are a traditional edible food used to treat hepatic disease. The anti‐obesity and hypolipidemic effects of mulberry water extracts (MWE) have attracted increasing interest. In the present study, MWE were assessed for their hepatic lipid‐lowering potential when administered in fatty acid overload conditions in HepG2 cells. RESULTS: We found that MWE significantly reduced lipid accumulation, suppressed fatty acid synthesis, and stimulated fatty acid oxidation. Furthermore, MWE also inhibited acetyl coenzyme A carboxylase activities by stimulating adenosine monophosphate‐activated protein kinase (AMPK). MWE attenuated the expression of sterol regulatory element‐binding protein‐1 (SREBP‐1) and its target molecules, such as fatty acid synthase. Similar results were also measured in the expressions of enzymes involved in triglyceride and cholesterol biosyntheses including glycerol‐3‐phosphate acyltransferase, 3‐hydroxy‐3‐methylglutaryl‐CoA reductase, and SREBP‐2. In contrast, the lipolytic enzyme expression of peroxisome proliferator activated receptor α and carnitine palmitoyltransferase‐1 were increased. CONCLUSIONS: Our study suggests that the hypolipidemic effects of MWE occur via phosphorylation of AMPK and inhibition of lipid biosynthesis. Therefore, the mulberry extract may be active in the prevention of fatty liver. Copyright © 2011 Society of Chemical Industry     

EGCG inhibits protein synthesis,lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells

In the previous studies, (–)‐epigallocatechin‐3‐gallate (EGCG) has been shown to have anticarcinogenic effects via modulation in protein expression of p53. Using p53 positive Hep G2 and p53 negative Hep 3B cells, we found that treatment of EGCG resulted in dose‐dependent inhibition of cellular proliferation, which suggests that the interaction of EGCG with p53 may not fully explain its inhibitory effect on proliferation. Caloric restriction (CR) reduces the incidence and progression of spontaneous and induced tumors in laboratory rodents. EGCG has multiple beneficial activities similar to those associated with CR. One key enzyme thought to be activated during CR is AMP‐activated kinase (AMPK), a sensor of cellular energy levels. Here, we showed that EGCG activated AMPK in both p53 positive and negative human hepatoma cells. The activation of AMPK suppressed downstream substrates, such as mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E‐binding protein‐1 (4E‐BP1) and a general decrease in mRNA translation. Moreover, EGCG activated AMPK decreases the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl‐CoA carboxylase (ACC). Interestingly, the decision between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive Hep G2 cells, EGCG blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up‐regulating p21 expression. However, EGCG inducted apoptosis in p53 negative Hep 3B cells. Based on these results, we have demonstrated that EGCG has a potential to be a chemoprevention and anti‐lipogenesis agent for human hepatoma cells.     

Inhibitory effect of esculetin on free-fatty-acid-induced lipid accumulation in human HepG2 cells through activation of AMP-activated protein kinase

Food Science and Biotechnology - This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a...     

Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet

BACKGROUND: Ginseng saponin and ginsenosides exert anti‐obesity effects via the modulation of physiological lipid metabolism in vivo or intracellular signalling in cell culture systems. However, the complicated relationship between the anti‐obesity effects of ginseng and gene expression has yet to be defined under in vivo conditions. Therefore, we evaluated the relationship between the anti‐obesity effects of Korean red ginseng extract (KRGE) and hepatic gene expression profiles in mice fed long‐term on a high‐fat diet (HFD) in this study. RESULTS: KRGE reduces the levels of cholesterol, low‐density lipoprotein‐cholesterol (LDL‐C), serum triglycerides, and atherogenic indices. Levels of leptin, adiponectin and insulin, which regulate glucose and lipid metabolism, were impaired profoundly by HFD. However, KRGE treatment brought these levels back to normal. KRGE was found to down‐regulate genes associated with lipid metabolism or cholesterol metabolism (Lipa, Cyp7a1, Il1rn, Acot2, Mogat1, Osbpl3, Asah3l, Insig1, Anxa2, Vldlr, Hmgcs1, Sytl4, Plscr4, Pla2g4e, Slc27a3, Enpp6), all of which were up‐regulated by HFD. CONCLUSION: KRGE regulated the expression of genes associated with abnormal physiology via HFD. Leptin, insulin, and adiponectin, which carry out critical functions in energy and lipid metabolism, were shown to be modulated by KRGE. These results show that KRGE is effective in preventing obesity. Copyright © 2011 Society of Chemical Industry     

Epigallocatechin gallate (EGCG) attenuates high glucose-induced insulin signaling blockade in human hepG2 hepatoma cells

Insulin resistance is the primary characteristic of type 2 diabetes which as a result of insulin signaling defects. It has been suggested that the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) displays some antidiabetic effects, but the mechanism for EGCG insulin-enhancing effects is incompletely understood. In the present study, the investigations of EGCG on insulin signaling are performed in insulin-responsive human HepG2 cells cotreated with high glucose. We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt. As the results, the insulin metabolic effects of glycogen synthesis and glucose uptake are inhibited by high glucose. However, the treatment of EGCG improves insulin-stimulated downsignaling by reducing IRS-1 Ser307 phosphorylation. Furthermore, we also demonstrated these EGCG effects are essential depends on the 5'-AMP-activated protein kinase (AMPK) activation. Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS-1 Ser307 phosphorylation through the AMPK activation pathway.     

Parthenolide inhibits lipid accumulation via activation of Nrf2/Keap1 signaling during adipocyte differentiation

Food Science and Biotechnology - The effects of parthenolide (PL), a sesquiterpene lactone obtained from feverfew plant, on lipid accumulation and signaling pathway in adipocytes were investigated....     

Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation

Natural herbal medications may be one answer to the worldwide epidemic of obesity. This study examines the effects of Cassia seed ethanol extract (CSEE) upon lipid accumulation in white adipose tissue (WAT). CSEE exhibited a significant concentration-dependent decrease in the intracellular accumulation of trigycerides in 3T3-L1 adipocytes. After being fed a high-fat diet (HFD) for 2 weeks, rats were fed CSEE (100, 200 or 300 mg/kg) once daily for 8 weeks. CSEE caused dose-related reductions in body weight gain (as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats). CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element-binding protein 1 and fatty acid synthase protein levels in epididymal WAT of HFD-fed rats. CSEE could attenuate lipid accumulation in WAT via AMPK signaling pathway activation.     

Synergistic effect of Korean red ginseng extract and GABA mixture on the IgE production in mice via Th1/Th2 cell balance

Food Science and Biotechnology - It has been recently reported that the immune system has been linked to the nervous system. This study was conducted to investigate the effect of administration of...     

Residual powders from Shochu distillation remnants induce apoptosis in human hepatoma cells via the caspase-independent pathway

Shochu distillation remnants (SDR) are by-products in the manufacturing process of the Japanese liquor Shochu and include various useful organic compounds derived from the fermentation of grains. We have obtained valuable powder (PSDR) from freeze-dried SDR by the treatment with ethanol. In this study, we examined the anticancer effects of barley-, rice-, and sweet potato-PSDR against HepG2 and HuH-7 cells of human hepatocellular carcinoma (HCC) in?vitro. All PSDR inhibited the growth of both these HCC cells through the induction of apoptosis. Especially, barley-PSDR was the most effective for the growth inhibition and apoptosis induction of HCC cells of all PSDR. We next examined the apoptotic mechanisms induced by barley-PSDR. Decrease in mitochondrial membrane potential and release of cytochrome c from mitochondria were observed in HCC cells after the treatment with barley-PSDR. Furthermore, barley-PSDR induced the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria, while it did not significantly affect the activities of caspase-3, -8, and -9. The results suggested that barley-PSDR induced apoptosis against HCC cells via the caspase-independent mitochondrial pathway. The findings in this study suggest that PSDR has the possibility of therapeutic and/or preventive agents of HCC.