• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.4
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• pp.395-401
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• 2006

In this study, we investigated anticarcinogenic effects of extracts from Gloiopeltis tenax (GT). GT was extracted with methanol (GTM), which was then further fractionated into four fractions by using solvent fractionation method, affording methanol (GTMM), hexane (GTMH), butanol (GTMB) and aqueous (GTMA) soluble fractions. We determined the cytotoxic effects of these fractions on cancer cells by MTT assay. Among various fractions of GT, the GTMM showed the strongest cytotoxic effect at concentration of $150{\mu}g/mL$, displaying 95.97% on HepG2 cell lines and 93.64% on HT-29 cell lines, respectively. And, the anti-proliferative effect of GT was accompanied by a marked in increase of levels of Bad, Bax, Bok and Bak protein and activation of caspase-3, caspase-7 and PARP protein. Also, we observed quinone reductase (QR) induced effects in all fraction layers of GT on HepG2 cells. The QR induced effects of the GTMM and GTMB on HepG2 cells at concentration of $60{\mu}g/mL$ showing inductive indexes of 2.86 and 2.04 compared to the control value of 1.0.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.420-428
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• 2023

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.136-142
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• 2002

Anticarcinogen is one of the major strategies for cancer control. It is well established that dietary factors play an important role in modulating the development of certain types of human cancer. We investiagted the anticarcinogenic effects of Sedum sarmentosum Bunge (SS) with Platycodon grandiflorum A. extracts on HepG2, HeLa and MCF-7 cell lines. By the MTT assay, among the five partition layers of methanol extract of SS (SSM), the ethylether partition layer of SS (SSMEE) showed the strongest cytotoxic effects on all cell lines. We also investigated the synergistic effect of the combination of SS and PG extracts on growth inhibition of the HepG2, HeLa and MCF-7 cell lines compared to the effects of five partition layers of SSM. Combination of SS and PG extracts significantly increased cytotoxic effects on all cell lines. Therefore, we were able to conclude that ethylether partition layer, SSMEE might have potentially useful cytotoxic materials on all the human cancer cells which we used. And we could suggest that the combination of SS with PG enhanced the anticarcinogenic effect on HepG2, HeLa and MCF-7 cell lines. We also determined QR activity of partition layers of SSM, among them, SSMEE on HepG2 cells showed the highest QR activity, 3.21 as control value of 1.0.

• Korean Journal of Food Science and Technology
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• v.43 no.6
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• pp.787-790
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• 2011

The objective of this study was to investigate the anticancer effects of Acer tegmentosum M. extracts. HepG2 hepatocarcinoma cells were treated with ethanol, chloroform, ethylacetate, butanol, aqueous fraction and hot water extract. The antiproliferative effect was evaluated by trypan blue exclusion, MTT-based viability assay and morphology. The trypan blue test showed that anticancer effect of the A. tegmentosum M. extracts on HepG2 cells increased gradually in proportion to the increasing concentration of the fractions. The butanol fraction showed the highest anticancer activity against HepG2 cells (p<0.05). The MTT assay indicated that the growth inhibition by the butanol fraction was dose-dependent. These results suggest that A. tegmentosum M. has the potential to inhibit the growth of hepatocarcinoma cells.

• Korean Journal of Food Science and Technology
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• v.53 no.3
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• pp.260-266
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• 2021

This study aimed to identify the hepatoprotective effects of a fermented Chrysanthemum indicum L. water extract. The extraction yield, antioxidant activities (ABTS and DPPH), and content of luteolin and luteolin-7-glucoside were significantly higher in the fermented C. indicum L. water extract (FCI) than in the C. indicum L. water extract. Treatment with FCI (200 ㎍/mL) significantly reduced the activities of gamma(γ)-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in HepG2 cells treated with 3% ethanol. Furthermore, FCI did not affect the viability of the HepG2 cells. These results suggest that FCI can be useful for the development of an effective hepatoprotective agent.

• Korean Journal of Pharmacognosy
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• v.53 no.3
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• pp.145-152
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• 2022

Type II diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance, and abnormally elevated hepatic gluconeogenesis is characterized. Phillyrin, one of the major active constituents of Forsythia suspense, is known to possess the anti-inflammatory and anti-oxidant effects. However, the anti-diabetes mellitus effect of phillyrin and its molecular mechanisms are unclear. The aim of the current study was to investigate the role of phillyrin on gluconeogenesis in insulin resistant HepG2 cells. Phillyrin suppressed high glucose (HG)-induced glucose production. In addition, phillyrin reduced HG-induced the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), major genes in hepatic gluconeogenesis. Phillyrin treatment attenuated HG-induced nucleus protein levels of FOXO1 and HDAC5 and increased the phosphorylation of Akt, AMPK, HDAC5, and FOXO1. The block of AMPK and Akt activity did not exert the inhibitory effect of phillyrin on gluconeogenesis in insulin resistant HepG2. Taken together, these results suggest that phillyrin inhibits gluconeogenesis of hepatocytes to improve glucose metabolism, through the regulation of LKB1/AMPK/HDAC5 and PI3K/AKT/FOXO1 pathway. These results indicate that phillyrin may be useful in improving hepatic gluconeogenesis associated with insulin resistant and T2DM.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.37.1-37.17
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• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• Journal of Environmental Health Sciences
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• v.30 no.3
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• pp.230-238
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• 2004

The adverse health effects of a number of environment pollutions are related to the formation of free radicals. Induction of antioxidant defensive system in the response to an oxidative attack is an essential element of the cell to survive. CYP2E1 is easily induced by organic solvents and induces continuous formation of reactive oxygen species (ROS). ${\gamma}$-Glutamyltranspeptidase (${\gamma}$GT) plays an important role in glutathione metabolism and xenobiotic detoxification. To evaluate the characteristic of oxidative stress which induces GGT expression and to understand human antioxidant defensive response against oxidative stress induced by CYP2E1, we studied regulation of ${\gamma}$GT enzyme expression in response to various oxidative stresses in human HepG2 cells. The ${\gamma}$GT activity was not modified after exposure of acute oxidative stress inducing agents (ferric nitrilotriacetate, cumene hydroperoxide, ADP-Fe, O-tetradecanoylphorbol-13-acetate, tumor necrosis factor-alpha). To induce continuous exposure of cells to ROS, HepG2 cells were transfected by human CYP2E1 gene transiently. The CYP2E1 activity was verified with chlorzoxazone hydroxylation. Transfection of CYP2E1 showed continuous 60% increase in intracellular ROS and 240 % increase in microsomal ROS. CYP2E1 overexpressing cells showed increased ${\gamma}$GT activity (2.5-fold). The observed enhancement of ${\gamma}$GT activity correlated with a significant increase of ${\gamma}$GT mRNA (2.1-fold). Treatment with antioxidant strongly prevented the increase in ${\gamma}$GT activity. The CYP2E1 overexpression did not modify toxicity index and increased glutathione levels. These results show that continuous exposure of cells to ROS produced by CYP2E1 up-regulates ${\gamma}$GT; This may be one of the adaptive antioxidant responses of cells to oxidative insult. Present study also suggests that the induction of ${\gamma}$GT could be used as a marker of oxidative stress induced by exposure to organic solvents.

• Journal of the East Asian Society of Dietary Life
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• v.19 no.3
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• pp.384-394
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• 2009

This study was performed to determine the antioxidative and anticancer effects of extracts from Adenophora remotiflora leaves. The antioxidative effects of the extracts were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging activity and hemoglobin-induced linoleic acid oxidative inhibition assays. The results indicated that the extracts had stronger effects than the synthetic antioxidant BHT at the same concentration. The $SC_{50}$ values (50% radical scavenging effect on $1{\times}10^{-4}$ M DPPH) of the methanol fraction, water extract, and BHT were 47.5 ${\mu}g$/mL, 74.6 ${\mu}g$/mL and 102.2 ${\mu}g$/mL, respectively. In addition the $IC_{50}$ values (hemoglobin-induced linoleic acid oxidation inhibition) of the methanol fraction, water extract, and BHT were 120.8 ${\mu}g$/mL, 135.6 ${\mu}g$/mL, and 150.2 ${\mu}g$/mL, respectively. This research also assessed decreases in the survival of BNLcl2 cells (normal liver cells) by solvent fractions of the A. remotiflora leaf extracts at various concentrations (1, 5, 10, 25, 50, 100, 250, 500, 1,000, 2,000 ${\mu}g$/mL). The water extract did not decrease survival at any of the concentrations when compared to the control group. The hexane, ethyl acetate, and methanol fractions decreased survival as compared to the control group by inducing cell toxicity at a concentration of 1,000 ${\mu}g$/mL and above. Therefore, an anticancer activity experiment was conducted using concentrations below 500 ${\mu}g$/mL. At 500 ${\mu}g$/mL, the methanol fraction decreased A549 cell (human lung carcinoma cells) survival by 46% as compared to the control group, presenting the greatest effect against cell survival. All extracts showed greater anticancer activity in Hep G2 cells (human liver carcinoma cells) as compared to the A549 cells. For the Hep G2 cells, the methanol extract decreased survival by 28% as compared to the control group at the concentration of 500 ${\mu}g$/mL, thus restraining lung cancer cell growth.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.1
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• pp.80-85
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• 2001

Various lines of evidence suggest that dietary components protect the initiation step of carcinogenesis. In this study, the ethylacetate (PGMEA), ethylether (PGMEE), butanol (PGMB) and aqueous (PGMA) soluble fractions of Punica granatum L. (PG) were screened for their growth inhibition using the MTT assay on HepG2, HeLa, C6, MCF-7 and HT-29 cells and for their activity to induce quinone reductase (QR) in HepG2 cells. Among various fractions of Punica granatum L., the PGMEE showed the strongest growth inhibition at 500 $\mu\textrm{g}$/mL which resulted 92.5% on Hela cell lines and 97.8% on C6 cell lines. The PGMEA and PGMB also showed significant growth inhibition. The assay of QR induction on HepG2 cells, grown in the presence of PGMEE at the concentration of 50$\mu\textrm{g}$/mL, was 1.4 times more effective compared with the control value of1.0. These results suggested that useful cancer chemoprevention materials could be isolated from PGMEE fraction of Punica granatum L.