• 대한한의학회지
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• 제41권4호
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• pp.64-71
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• 2020

Objectives: This study was done to look into whether Nrf2 take some role in the anti-lipogenic effect of kaurenoic acid in a nonalcoholic fatty liver disease (NAFLD) cellular model. Materials and Methods: We measured the effect of kaurenoic acid on intracellular steatosis and Nrf2 activation. Next, the effect of kaurenoic acid on SREBP-1c and some lipogenic genes in palmitate treated HepG2 cells with or without Nrf2 silencing. Results: The increased SREBP-1c expression was significantly decreased by concomitant kaurenoic acid treatment in non-targeting negative control siRNA transfected HepG2 cells. However, kaurenoic acid did not significantly inhibited increased SREBP-1c level in Nrf2 specific siRNA transfected HepG2 cells Conclusions: Kaurenoic acid has a potential to activate Nrf2, which may suppress SREBP-1c mediated intracellular steatosis in HepG2 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.107-115
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• 1997

We studied the effects of bile acids on the induction ofapoptosis in HepG2 human hepatocellular carcinoma cells. Treatment with either ursodeoxycholic acid (UDCA) or lithocholic acid (LCA) resulted in a dose- and time-dependent decrease in cell viability assessed by MTT assay. Both UDCA and LCA also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which these bile acids induce cell death was through apoptosis. Cycloheximide, a protein synthesis inhibitor, blocked the apoptosis induced by these bile acids, implying that new protein synthesis may be required for the apoptosis. Intracellular $Ca^{2+}$ release blockers (dantrolene and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester) inhibited decreased cell viability and DNA fragmentation induced by these bile acids. Treatment of HepG2 cells with calcium ionophore A23l87 induced DNA fragmentation. These results suggest that UDCA and LCA induce apoptosis in the HepG2 cells and that the activation of intracellular $Ca^{2+}$ signals may play an important role in the apoptosis induced by these bile acids.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.183-191
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• 2008

Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.

• 한국식품저장유통학회지
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• 제30권5호
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• pp.797-810
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• 2023

Elaeagnus umbellata leaves have been reported to suppress inflammation, allergic responses, lung cancer proliferation and oral bacterial growth. Cadmium (Cd) is a heavy metal that has been found to cause many toxicities, including liver toxicity. The aim of this study was to evaluate the capacity of 70% ethanol extract of E. umbellata leaves (EUL) to protect human hepatocytes from Cd toxicity. After exposure of HepG2 cells to Cd at 10 𝜇M for 24 h, cell viability, expression levels of apoptosis- and antioxidant-related proteins, reactive oxygen species (ROS) accumulation and Cd uptake were assessed. EUL protected HepG2 cells from Cd-induced apoptosis as determined by MTT assay. A decrease in caspase-3 and p-p53 protein levels was observed in cells pretreated with EUL prior to Cd exposure. Furthermore, the Cd-induced increase in intracellular DCF fluorescence was attenuated by EUL, indicating that the Cd-induced apoptosis preventing effect was associated with the suppression of ROS accumulation. Moreover, EUL's effects on the inhibition of p38, JNK, and AKT phosphorylation also appear to be associated with protection against Cd toxicity. Moreover, EUL upregulated Cd-depressed expression of Nrf2, HO-1, catalase, and MT-1,2 proteins, suggesting that Cd uptake-induced apoptosis in HepG2 cells may be inhibited by EUL's antioxidative potential.

• Journal of Microbiology and Biotechnology
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• 제34권5호
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• pp.1082-1091
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• 2024

The antioxidant capacity and protective effect of peptides from protein hydrolysate of Cordyceps militaris cultivated with tussah pupa (ECPs) on H₂O₂-injured HepG2 cells were studied. Results indicated ECP1 (<3 kDa) presented the strongest antioxidant activity compared with other molecular weight peptides. Pretreated with ECPs observably enhanced survival rates and reduced apoptosis rates of HepG2 cells. ECPs treatment decreased the ROS level, MDA content and increased CAT and GSH-Px activities of HepG2 cells. Besides, the morphologies of natural peptides from C. militaris cultivated with tussah pupa (NCP1) and ECP1 were observed by scanning electron microscopy (SEM). Characterization results suggested the structure of NCP1 was changed by enzymatic hydrolysis treatment. Most of hydrophobic and acidic amino acids contents (ACC) in ECP1 were also observably improved by enzymatic hydrolysis. In conclusion, low molecular weight peptides had potential value in the development of cosmetics and health food.

• 한국미생물·생명공학회지
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• 제47권1호
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• pp.43-53
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• 2019

The anticancer activity of guava (Psidium guajava L.) leaf extract (GLE) occurs via the induction of apoptosis in cancer cells. However, the mechanism behind GLE-induced apoptosis in the human hepatocellular carcinoma cell line HepG2 remains unclear. In the present study, we investigated the apoptotic effects and mechanism of action of GLE in cultured HepG2 cells. The results showed that GLE induced reactive oxygen species (ROS) synthesis and disrupted the mitochondrial membrane potential (${\Delta}{\Psi}m$). Moreover, GLE increased the expression of apoptotic pathway proteins, such as the cleaved forms of caspase-3, -8, and -9; the translocation of Bax and cytochrome c (cyt-c) from the mitochondria to the cytosol; and the downregulation of Bcl-2. In addition, p53 protein expression was increased upon GLE treatment. These observations indicate that the GLE-induced apoptosis in HepG2 cells is mediated by mitochondrial ROS generation, followed by caspase activation and cyt-c release, suggesting that GLE may be a promising candidate for the development of novel drugs for the treatment of liver cancers.

• BMB Reports
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• 제29권1호
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• pp.73-80
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• 1996

The effect of albumin on phosphatidylcholine (PC) metabolism in Hep-G2, 3T3-H.ras, and 3T3 cells pre-labelled with [Me-$^3H$]choline was studied. The [$^3H$]choline was more efficiently taken up and incorporated into cellular phospholipids in 3T3-H.ras cells than in Hep-G2 and 3T3 cells. In each of the three cell lines, most of the [$^3H$]choline metabolized into the phospholipids was incorporated into PC and only minor was incorporated into lysophosphatidylcholine (LPC). Bovine serum albumin stimulated the release of [$^3H$]LPC and [$^3H$]PC from each of the three cell lines pre-labelled with [$^3H$]choline. [$^3H$]PC was also released in the absence of albumin but [$^3H$]LPC was not. The efficiency of LPC secretion represented as the proportion of medium [$^3H$]LPC to cellular [$^3H$]choline lipid during a chase period is approximately 9 to 14 times greater in 3T3 cells compared with the transformed 3T3-H.ras and Hep-G2 cells. A similar comparison of published data for rat hepatocytes with Hep-G2 shows secretion to be 35~75 times greater from the rat hepatocytes than from Hep-G2. Also, PC secretion from 3T3 cells was 1.6 times more effective than from 3T3-H.ras, whereas rat hepatocytes secrete PC 2.8~3.8 times more effectively than does Hep-G2. The measurement of specific radioactivity of cellular PC in pre-labelled 3T3 cells showed it to be similar to that of the secreted PC. However, the specific radioactivity of secreted LPC was markedly lower than that of the cellular PC, which suggests that LPC is being secreted from a PC pool distinct from that used for PC secretion.

• Preventive Nutrition and Food Science
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• 제8권3호
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• pp.284-288
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• 2003

In this study, we investigated the effects of green tea and Pueraria radix tea on the production of Apo B$_{100}$ in Hep G$_2$ liver cells and on the expression of the low density lipoprotein (LDL) receptor. Treatment with green tea resulted in a 60.7% decrease on the Apo B$_{100}$ concentration in Hep G$_2$ cells. Pueraria radix tea decreased Apo B$_{100}$ concentration by 63.5% in Hep G$_2$ cells. Green tea and Pueraria radix tea significantly decreased Apo B$_{100}$ concentration by 64.8% and 61.8%, respectively, in the media. Treatment of the cells with green tea and Pueraria radix tea also significantly decreased the intracellular total cholesterol, but total cholesterol concentrations in the media increased by 26.4% (green tea) and 23.6% (Pueraria radix tea) above that measured in the media of control cells. The addition of green tea and Pueraria radix to the media of the Hep Gz cells increased the LDL receptor binding activities by 84.1% and 79.4%, respectively.

• Nutrition Research and Practice
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• 제11권2호
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• pp.97-104
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• 2017

BACKGROUND/OBJECTIVE: Although Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Asian, its functionality and mechanism of action. The aim of this study was to determine the protective effect of ethanol extract of AK (AK-Ex) on acute hepatotoxicity induced by acetaminophen (AAP) in HepG2 human hepatocellular liver carcinoma cells and HepaRG human hepatic progenitor cells. MATERIALS/METHODS: AK-Ex was prepared HepG2 and HepaRG cells were cultured with various concentrations and 30 mM AAP. The protective effects of AK-Ex against AAP-induced hepatotoxicity in HepG2 and HepaRG cells were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, lactate dehydrogenase (LDH) assay, flow cytometry, and Western blotting. RESULTS: AK-Ex, when administered prior to AAP, increased cell growth and decreased leakage of LDH in a dose-dependent manner in HepG2 and HepaRG cells against AAP-induced hepatotoxicity. AK-Ex increased the level of Bcl-2 and decreased the levels of Bax, Bok and Bik decreased the permeability of the mitochondrial membrane in HepG2 cells intoxicated with AAP. AK-Ex decreased the cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of caspase-9, -7, and -3. CONCLUSIONS: These results demonstrate that AK-Ex downregulates apoptosis via intrinsic and extrinsic pathways against AAP-induced hepatotoxicity. We suggest that AK could be a useful preventive agent against AAP-induced apoptosis in hepatocytes.

• 한방안이비인후피부과학회지
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• 제19권3호통권31호
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• pp.22-33
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• 2006

Objective : Angiogenesis induced by hypoxia and inflammation are an essential process of solid tumors and psoriasis. We researched the HIF-1 ${\alpha}$ (hypoxia inducible factor 1 alpha), VEGF(Vascular Endothelial Growth Factor), survival related PI3K-Akt, and inflammation related COX-2 protein expressions to get the information of the mechanism and effects of Rehmannia glutinosa in HepG2 and HaCaT cell lines. Method : To investigate the roles of the Rehmannia glutinosa extract, we performed MTS assay and western blots using HaCaT cells and HepG2 cells. HaCaT cells and HepG2 cells were treated with $50{\mu}g/ml$ and $100{\mu}g/ml$ Rehmannia glutinosa extracts. After 4hrs, HaCaT cells were treated with IGF-II protein for 24hrs and HepG2 cells were treated with $CoCl_2$. Results : 1. We could ohserve that the reduction of the protein level of HIT-1 ${\alpha}$ induced by IGF-II in HaCaT cells. 2. We Could ohserve that the decreased PI3K-Akt and COX-2 expression level by Rehmannia glutinosa extracts treated in HaCaT cells independently ith ERK1/2. 3. We could observe that the reduction of the protein level of HIF-1 ${\alpha}$ induced by $CoCl_2$ in HepG2 cells. Conclusion : These results suggest that Rehmannia glutinosa extracts contributes to the anti-survival pathway and anti-inflammatory activities. Also, we could assume that Rehmannia glutinosa act as anti-inflanmmatory or anti-hypoxia agents via reduction of COX-2 and HIF-1 ${\alpha}$.