• Nutritional Sciences
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• v.4 no.1
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• pp.26-33
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• 2001

Animal and clinical studies as well as epidemiological data have provided convincing evidence that n-3 polyunsaturated fatty acids can protect against atherosclerosis. However, the effects of the fatty acids on atherogenesis are contradictory. This discrepancy could derive from great susceptibility of the fatty acids to oxidation. We investigated the effect of eicosapentaenoic aced(EPA) on cellular atherogenesis via the scavenger receptor of THP-1 derived macrophages. THP-1 cells were fully differentiated into macrophages by incubating with phorbol 12-myristate 13-acetate for seven days. Atherogenic features of EPA were compared by subsitituting for linoleic acid (LA). Macrophages were also incubated without treatment of the fatty acids as controls. EPA (5-50 nmol/mL) was not cytotoxic and did not measurably induce cellular oxidation compared to bovine serum albumin (BSA) vehicle or identical doses of LA. EPA increased macrophage uptake and degradation of acetylated LDL(AcLDL) up to 14% and 88%, respectively. EPA increased markedly total cellular sterol synthesis and heparin-releasable lipoprotein lipase activity of macrophages, indicating that EPA may enhance accumulation of cellular cholesteryl ester and possibly facilitate formation of foam cells. These results demonstrate that EPA promotes the modified LDL-triggered atherosclerotic process by the modulation of the scavenger receptor and the activation of LPL in macrophages.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.770-775
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• 2014

The green microalga of the genus Nannochloropsis (class Eustigmatophyceae) is a leading candidate for biofuel production due to its ability to accumulate high oil content (28.7% of cellular ash-free dry weight). We investigated the anti-inflammatory and anticancer activities of sterol-rich fraction from nannochloropsis oculata n-hexane (NOH) extract after saponification of the microalga. Among the fractions with n-hexane, chloroform and ethyl acetate, the n-hexane fraction showed the highest anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophage as well as anticancer activity against human leukemia HL-60 cells without the cytotoxity. And the sterol-rich fraction was obtained from the n-hexane fraction by open silica column under the gradient solvent condition with 100% hexane (1L), hexane : ethyl acetate (20 : 1, 10 : 1, 5 : 1, 1 : 1, v/v). Among the four fractions (NOH-1~4), especially NOH-1 contained the highest content of sterols. NOH1 showed the highest HL-60 (about 85%) and NO inhibitory activities at the concentration of $100{\mu}g/mL$. These results demonstrated that the sterol-rich fraction from N. oculata might be a useful candidate as anti-inflammatory and anticancer agents for anti-inflammatory and anticancer activity.

• Biomedical Science Letters
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• v.6 no.4
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• pp.237-244
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• 2000

It has been reported that plasma membrane activity of the spermatozoa may be susceptible to be influenced by extracellular osmolality and such membranous changes involve infracellular molecular changes, special regard to the structure of membranous lipids, and the accompanying ion-channel of which are closely related with their fluidity of $Ca^{2+}$ and HCO$^{-}_{3}$. It is of common recognition that a certain kind of sterol acceptor player an important to induce lipid fluctuation of the sperm plasma membrane which have been influenced by BSA administration and came in effect to outflow of cholesterol from the spermatozoa and resulted in changes of ionic fluidity to facilitate adenylyl cyclase, and to induce protein tyrosine phosphorylation by increase of cAMP and activation of PKA. Thus it seems likely that an augmentation of the acrosomal reaction is closely related with protein tyrosine phosphorylation. The following experimental results were obtained in the present study; Under the high osmolality conditions, the spermatozoa motility declined significantly and the structural change of the plasma membrane diminished to confirm that the response degrees to the osmolality depended upon the water transfer volume through the plasma membrane and the changes of cellular volume. Those experimental results suggest that a physiological parameter such as low temperature condition played an important role for presentation of spermatozoa and that inducement of spermatozoa activation for reinforcement of protein tyrosine phosphorylation. On the other hand, it seemed likely that the BSA administration as one of sterol accepters might represent a key role also under the high osmolality condition and their result also suggests that osmolality change, special regard to high osmolality condition may play an important role also in the processes of signal transmission.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1649-1654
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• 2016

Tea derived from the leaves and buds of Camellia sinensis (Theaceae) is consumed worldwide. Green tea contains various components with specific health-promoting effects, and is believed to exert protective effects against diseases including cancer, diabetes and hepatitis, as well as obesity. Of the various tea components, the polyphenol catechins have been the subject of extensive investigation and among the catechins, (-)-epigallocatechin gallate has the strongest bioactivity in most cases. Our research group has postulated that hepatocyte nuclear factor-$4{\alpha}$, sterol regulatory element-binding proteins, and tumor necrosis factor-${\alpha}$ are targets of green tea constituents including (-)-epigallocatechin gallate for their anti-diabetes, anti-obesity, and anti-hepatitis effects, respectively. Published papers were reviewed to determine whether the observed changes in these factors can be correlated with anti-cancer effects of green tea. Two major action mechanisms of (-)-epigallocatechin gallate have been proposed; one associated with its anti-oxidative properties and the other with its pro-oxidative activity. When reactive oxygen species are assumed to be involved, our findings that (-)-epigallocatechin gallate downregulated hepatocyte nuclear factor-$4{\alpha}$, sterol regulatory element-binding proteins, and tumor necrosis factor-${\alpha}$ may explain the anti-cancer effect of green tea as well. However, further studies are required to elucidate which determinant directs (-)-epigallocatechin gallate action as an anti-oxidant or a pro-oxidant for favorable activity.

• Journal of Ginseng Research
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• v.29 no.4
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• pp.159-166
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• 2005

Ginsenosides, a group of Panax ginseng saponins, exert the lowering effects of plasma cholesterol levels in animals. We had reported earlier that ginsenoside Rb2 upregulate low-density lipoprotein receptor (LDLR) expression via a mechanism that is dependent of the activation of sterol response element binding protein 2 (SREBP-2) expression. This study was conducted to determine the effects of ginsenoside Rb2 on the expression of the hepatic LDLR expression at cellular levels using HepG2 cells, and to evaluate whether the sterol response element binding protein 1 (SREBP-l) was involved in the regulation of LDLR expression. Incubation of HepG2 cells in serum-free medium supplemented with cholesterol $(10{\mu}g/ml)$ for 8 hours decreased the mRNAs of LDLR mRNA by $12\%$ and SREBP-l mRNA by $35\%$. Ginsenoside Rb2 antagonized the repressive effects of cholesterol and increased both LDLR and SREBP-l mRNA expression to 1.5- and 2-fold, respectively. Furthermore, Western blot and confocal microscopic analyses with SREBP-l polyclonal antibody revealed that ginsenoside Rb2 enhanced the maturation of the SREBP-1 from the inactive precursor form in ER membrane to the active transcription factor form in nucleus. These results suggest that ginsenoside Rb2 upregulates LDLR expression via a mechanism that is dependent of the activation of not only SREBP-2 expression, but also SREBP-1 expression and maturation, and also indicate that the pharmacological value of ginsenoside Rb2 may be distinguished from that of lovastatin which is reported that it upregulate LDLR through SREBP-2 only, not through SREBP-1.

• BMB Reports
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• v.43 no.2
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• pp.140-145
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• 2010

The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regulation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramatically increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-$\alpha$ (C/EBP-$\alpha$) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regulatory- element-binding protein (SREBP)-1c protein were induced on day 4. Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Collectively, our findings suggest that the adipogenic differentiation of porcine muscle satellite cells and a succeeding extensive adipogenesis, which is triggered by high glucose, is initiated by the mTOR signal pathway through the activation of SREBP-1c protein. This process is previously uncharacterized and suggests a cellular mechanism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.

• The Journal of Internal Korean Medicine
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• v.39 no.3
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• pp.302-312
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• 2018

Objectives: This study was performed to investigate the effects of two herbal medicines, Agastachis Herba and Lysimachiae Herba, on a cellular model of non-alcoholic fatty liver diseases (NFLDs). Methods: HepG2 cells were treated with palmitic acid and with various concentrations of Agastachis Herba (AH) or Lysimachiae Herba (LH) extract in water. The lipotoxicity was assessed using EZ-cytox, and the lipoapoptosis was assessed using cell death detection ELISA. Intracellular lipids were measured by oil red O staining. The efficacy of AH and LH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in HepG2 cells was measured by reverse transcription polymerase chain reaction (RT-PCR). Results: Both AH and LH extracts increased lipoapoptosis and decreased lipotoxicity and levels of SREBP-1c, ACC, and FAS (SREBP-1c, ACC, and FAS are factors in lipid synthesis). In the oil red O staining experiment, both extracts also reduced intracellular lipid accumulation; in this instance, LH's efficacy was superior to that of AH. Conclusions: According to the results, both AH and LH are likely to contribute to non-alcoholic fatty liver disease, as both interfere with lipid synthesis.

• Herbal Formula Science
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• v.24 no.2
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• pp.100-107
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• 2016

Objectives : The purpose of this study is to evaluate the anti-lipogenic effect of Sobuncheong-eum on non-alcoholic fatty liver disease in free fatty acid induced cellular model. Methods : HepG2 cells were treated with palmitate for 24h to overload intracellular triglyceride (TG) content in the presence or absence of Sobuncheong-eum extract. After palmitate treatment, Intracellular TG content was measured with TG assay kit. Several lipogenesis related markers, including AMP-activated protein kinase (AMPK), sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), were assessed using Western-blot analyses and RT-PCR. Results : Palmitate markedly increased intracellular TG in HepG2 cells, and which were alleviated by coadministered Sobuncheong-eum extract. Sobuncheong-eum extract activated AMPK, which plays a key role in reducing hepatic lipid accumulation, and reduced lipogenic fators, SREBP-1c, ACC, and FAS. Conclusions : Taken together, it is conceivable that Sobuncheong-eum has an potential to alleviate steatosis, and which may be mediated by activating AMPK at least in part.

• Molecules and Cells
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• v.19 no.2
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• pp.279-282
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• 2005

In mammals, 7-dehydrocholesterol reductase (Dhcr7) is the terminal enzyme in cholesterol biosynthesis. We previously reported that the Dhcr7 proximal promoter (-179 to +1), which contains CpG islands, is responsible for sterol-mediated expression of the rat gene. In the present study, we examined whether methylation of this region affects the transcriptional activity of the Dhcr7 gene. In vitro DNA methylation of the Dhcr7 promoter and luciferase-reporter assays showed that DNA methylation of the CpG islands suppressed transcription. Furthermore, treatment of the methylated Dhcr7 promoter with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-CdR), reversed the suppression of promoter activity. These results indicate that methylation of the CpG islands is an important transcriptional regulatory mechanism in the Dhcr7 promoter.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.74-79
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• 2015

Objectives: Here we investigated the anti-lipogenic potential of kaurenoic acid (KA), a diterpene derived from Aralia continentalis, in a cellular model of non-alcoholic fatty liver disease. Methods: HepG2 cells were treated with palmitate for 24h to induce intracellular lipid accumulation. To assess the influence of KA on steatotic HepG2 cells, various concentration of KA was co-administered. After palmitate treatment, Intracellular triglyceride content was measured. Expression level of several lipogenic genes, sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1) were measured using Western-blot analyses or RT-PCR. Results: Palmitate markedly increased intracellular triglyceride level and expression of related lipogenic genes in HepG2 cells, and which was relieved by co-administered KA. Conclusions: It is conceivable that that KA may have a pharmacological potential to reduce lipid accumulation in non-alcoholic fatty liver disease.