• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.213-219
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• 2011

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.

• Herbal Formula Science
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• v.26 no.3
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• pp.183-193
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• 2018

Objectives : In Traditional Korean Medicine, Epimedium koreanum Nakai has diverse pharmacological activities to treat impotence, forgetfulness, cataract and exophthalmos. Present study investigated anti-fibrogenic effects of E. koreanum water extract (EKE) in hepatic stellate cells (HSCs). Methods : To study anti-fibrogenic effects of EKE, LX-2 cells, a human immortalized HSCs, were pre-treated with $3-300{\mu}g/mL$ of EKE, and then subsequently exposed to 5 ng/mL of transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$). Expression level of ${\alpha}-smooth$ muscle actin was determined by immunoblot analysis. Phosphorylation of Smad, transactivation of Smad, and expression of plasminogen activator inhibitor-1 (PAI-1) were monitored to investigate the effect of EKE on $TGF-{\beta}1-mediated$ signaling pathway. Results : Up to $100{\mu}g/mL$, EKE did not show any cytotoxicity on LX-2 cells. Pre-treatment of EKE ($100{\mu}g/mL$) significantly inhibited ${\alpha}-smooth$ muscle actin expression induced by $TGF-{\beta}1$. In addition, EKE significantly decreased Smad2 and Smad3 phosphorylations, Smad binding element-driven luciferase activity and PAI-1 expression by $TGF-{\beta}1$. Of three flavonoid compounds found in EKE, only quercertin ($30{\mu}M$) attenuated $TGF-{\beta}1-mediated$ PAI-1 expression. Conclusion : These results suggest that EKE has an ability to suppress fibrogenic process in HSCs via inhibition of $TGF-{\beta}1/Smad$ signaling pathway.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.49-55
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• 2013

Objectives : Mori Folium was popularly used as one of the traditional medicinal herbs. Although M. Folium has been cultivated for rearing silkworm historically, it's use has been expanded as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. However, little has been known about the effect of M. Folium on liver fibrosis. Therefore, we would like to explore an anti-fibrogenic potential of M. Folium extract (MFE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the effects of MFE on the transforming growth factor ${\beta}1$ ($TGF{\beta}1$)-induced liver fibrosis in LX-2 cells. Cell viability, Smad binding element-driven luciferase activity, phosphorylations level of Smad 2/3, and expression level of $TGF{\beta}1$-dependent target genes were monitored in the MFE-treated LX-2 cells. Results : Up to 30 ${\mu}g/ml$ MFE treatment did not show any possible toxic effect in LX-2 cells. MFE inhibited $TGF{\beta}1$-inducible Smad binding element-driven luciferase activity and decreased the $TGF{\beta}1$-inducible phosphorylations of Smad 2 and Smad 3 in hepatic stellate cell in a dose dependent manner. Furthermore, increases of plasminogen activator inhibitor type 1, $TGF{\beta}1$ and matrix metalloproteinases 2 genes by $TGF{\beta}1$ were also attenuated by MFE treatment. Conclusions : These findings suggested that MFE would be used as a potential therapeutic agent for the treatment liver fibrosis, which might be mediated by the inhibition of $TGF{\beta}1$-inducible Smad 2/3 transactivation and target genes expression.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.45-53
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• 2013

Korean red ginseng, the processed root of Panax ginseng Meyer, has been frequently used for various therapeutic purposes in oriental medicine. The present study investigated the possible effect of Korean red ginseng extract (RGE) for the treatment of liver fibrosis in mice injected with carbon tetrachloride ($CCl_4$) for 4 wk. Liver injuries were assessed by blood biochemistry and histopathology in mice treated with $CCl_4$ alone or $CCl_4$+ RGE (30, 100, and 300 mg/kg). Concomitant treatment with RGE and $CCl_4$ (three times/wk for 4 wk) effectively inhibited liver fibrosis as evidenced by decreases in plasma alanine and aspartate aminotransferases, as well as by the percentages of degenerative regions, numbers of degenerative hepatocytes, and collagen accumulation in hepatic parenchyma. Treatment with $CCl_4$ for 4 wk increased mRNA levels of transforming growth factor ${\beta}1$ and plasminogen activator inhibitor 1 in fibrogenic liver, whereas RGE (30, 100, and 300 mg/kg) significantly blocked the induction of fibrogenic genes by $CCl_4$. Similarly, RGE also prevented transforming growth factor ${\beta}1$-mediated induction of fibrogenic genes in human hepatic stellate cell lines. More importantly, RGE markedly reduced the number of ${\alpha}$-smooth muscle actin-positive cells in liver tissue. This study implies that RGE efficaciously protects against the liver fibrosis induced by chronic $CCl_4$ treatment, and may therefore have potential to treat liver disease.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.116-126
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• 2023

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.32-32
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• 2003

소 난자의 체외성숙 과정에서 세포질 내 단백질의 생산과 축적의 변화는 핵 및 세포질 성숙과 밀접한 관계가 있다는 보고가 있지만, 난자의 성숙과 관련된 특정 단백질의 종류에 대한 보고는 없었다. 따라서 본 연구는 한우 난자의 체외성숙과 관련된 단백질의 생산 및 축적의 변화와 그 종류에 대해서 검토하였다. 체외성숙 시간(4.5, 9, 13.5, 18 및 24시간)에 따른 배양액 내의 단백질 합성의 변화는 2D gel electrophoresis를 이용하였고, 단백질 spot에 대해서는 peptide mass fingerprinting(PMF) 방법을 이용하였다. 또한 단백질 측정 시간에 신선 체외성숙 배양액으로 교환 후 난포란의 핵성숙과 배발달율을 검토하였다. 그 결과 한우 난포란의 체외성숙 시간에 따라 배양액에서 단백질의 양 및 질적인 변화를 확인하였다. 그리고 총 296개 단백질 spot들을 확인하였고, 그 중 30개 spot에서 유의적인 변화가 인정되었다. 또한 유의적인 변화를 보인 spot에 대한 PMF 분석을 통하여 Apolipoprotein A-1 precursor, Alpha enolase, Aldose reductase, 43kDa collectin precursor, Heat shock 27kDa protein, Plasminogen activator inhibitor-1 precursor, Thrombospondin 1 및 Transitional endoplasmic reticulum ATPase가 동정되었다 그리고 총 단백질 합성 경향은 0∼4.5 시간에는 감소하였고, 13.5∼18시간에 증가 한 후 다시 감소하는 경향을 나타내었으며, 단백질의 종류도 시간대별로 현저한 변화가 있었다. 한편 단백질을 측정하는 시기에 신선 체외성숙 배양액으로 교환한 후 난포란의 핵성숙 및 배발달율을 검토한 결과 18시간 체외성숙군에서 9시간째의 교환이 유의적으로 높은 핵성숙을 나타내었으나, 배발달율에서는 유의성이 인정되지 않았다. 그러나 24시간 체외성숙군에서 18시간째의 배양액 교환은 8세포기 및 배반포 발달율이 유의적(P<0.05)으로 높았다. 연구 결과로부터 소 난자의 체외성숙 시간에 따른 단백질 합성 경향의 차이를 확인하였고, 유의적인 변화를 나타낸 8가지의 단백질을 분리할 수 있었으며, 향후 이들 작용기전에 대한 연구가 필요하다고 사료된다.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• Nutritional Sciences
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• v.1 no.1
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• pp.70-76
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• 1998

This study was designed to investigate the relationship between body mass index (BMI) and dietary intake, and the relationship between BMI and plasma lipid levels in Korean adults. This study was conducted from January 1 to December 31 of 1997. It consisted of 3781 subjects (men 2402, women : 1379) with the majority between the ages of 40 and 59. The dietary assessment was based upon a twenty-four-hour food record. Subjects were classified into one of four reference BMI groups : underweight ($\leq 20 kg/m^2$), normal (20.1-25.0 kg/$m^2$), overweight (25.1-30.0 kg/$m^2$), and obese (>30 kg/$m^2$). The biochemical assessment included measurements of plasma total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglyceride (TG), lipoprotein (a), and plasminogen activator inhibitor-1 (PAI-1). The BMI study showed that 60.5% of the men measured were normal and 32.6% of the men were overweight and/or obese subjects. Sixty-four percent of the women were normal and 20.3% of the women measured were overweight and/o. obese subjects. With respect to the daily energy intake of the men and women subjects, the levels of daily energy intake appeared to increase as values of BMI increased. Men of the overweight group had significantly higher protein, fat and cholesterol intake than those of the normal or the underweight groups. The alcohol intake of the men in the overweight group was also significantly higher than that of the men in the underweight group. With respect to percent energy intake of macronutrients, there was no significant difference between the four BMI groups and percent energy intake for all the subjects in the study. The ratio of percent energy intake of carbohydrates : protein : fat : alcohol of the normal women group was 62 : 17 : 20 : 1, respectively. Women apparently had a higher intake of carbohydrates than men (52 : 17 : 19 : 10). With respect to the levels of plasma TC, LDL-C, TG, and HDL-C, the levels of plasma TC, LDL-C and TC appeared to increase as the values of BMI increased, while the level of HDL-C appeared to decrease as values of BMI increased. Levels of lipoprotein (a) appeared to be inversely related to the values of BMI, and levels of PAI-1 appeared to increase as values of BMI increased. The results of this study demonstrate that there is a relationship between dietary intake and BMI, and that there is a relationship between BMI and blood lipids levels.

• Journal of Life Science
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• v.22 no.10
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• pp.1371-1377
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• 2012

Fibrosis in kidney by internal and external factors causes progressive loss of renal function. Renal fibrosis is the inevitable consequence of an excessive accumulation of the extracellular matrix. TGF-${\beta}$ plays an important role in the process of renal fibrosis and stimulates the synthesis of profibrotic factors, including collagens, fibronectin, and plasminogen activator inhibitor (PAI-1). We examined the effect of Moringa oleifera Lam (moringa) extracts in a rat kidney fibrosis model. We found that moringa root extract suppresses protein expression/mRNA levels of Type I collagen, fibronectin, and PAI-1 induced by TGF-${\beta}$ in renal fibroblasts. Moringa root extract selectively inhibited phosphorylation of TGF-${\beta}$-induced $T{\beta}RII$ and the downstream signaling pathway (e.g., Smad4), and phospho-ERK, but not JNK, p38, or PI3K/AKT. These results suggest that moringa root extract can act against TGF-${\beta}$-induced renal fibrosis in rat kidney fibroblast cells by a mechanism related to its antifibrotic activity, which regulates expression of fibronectin, Type I collagen, and PAI-1 through $T{\beta}RII$-Smad2/3-Smad4 and ERK. Therefore, moringa root extract is an effective substance for fibrosis therapy and provides a new therapeutic strategy for diseases associated with elevated profibrotic factor synthesis.

• Korean Journal of Community Nutrition
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• v.6 no.1
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• pp.51-68
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• 2001

This investigation studied the relationship between Body Mass Index(BMI) and dietary intake, levels of serum lipid, lipoprotein(a) and plasminogen activator inhibitor-1(PAI-1) of 28.449 Korean adults(16.937 men, 11.542 women) from 1995 to 1999. The dietary assessment was conducted using 24-hour dietary records and food frequency questionnaires. During this five year study, the BMI normal-weight group, as a percentage of the annual test population, decreased from 68.0% to 60.2%, while the BMI overweight and obese groups collectively increased from 25.0% to 29.7%. The levels of serum total cholesterol (TC), LDL-cholesterol(LDL-C), Triacylglycerol(TG) and PAI-1 increased as the values of BMI increased, while the levels of HDL-cholesterol(HDL-C) and lipoprotein(a)(men only) appeared to decrease as values of BMI increased. The levels of daily energy intake also increased as values of BMI increased in both men and women. The obese group had significantly higher levels of carbohydrate, protein, fat(men only), and cholesterol intake than those of the normal-weight, underweight, and overweight groups. In men, BMI positively correlated with the levels of macronutrients and cholesterol intake(p＜0.001), % energy of protein, fat, and alcohol intake(p＜0.001), and the levels of serum TC, LDL-C, TG and PAI-1(p＜0.001), while BMI negatively correlated with % energy of carbohydrate intake, and the levels of Lp(a) and HDL-C(p＜0.001). In women, BMI negatively correlated with level of cholesterol(p＜0.01), fat(p＜0.001), alcohol intake(p＜0.05),% energy of fat (p＜0.001), % energy of alcohol intake and level of and HDL-C(p＜0.001). Subjects who had serum TC, LDL-C, HDL-C, and TG levels greater than the standard reference values(TC＞240mg/㎗, LDL-C＞130mg/㎗, HDL-C＞35, TG＞200mg/㎗) exhibited a higher intake of the three macronutrients, iron, calcium, meat, milk and fatty foods than those subjects who had serum lipid concentrations less-than-or-equal-to the standard reference values. Overall, there was positive correlation between the high risk factors of vascular disease variables, dietary intake, and BMI. Prevalence of hypertension and high blood sugar were increased as BMI increased, but the prevalence of hypertension is decreased as the year goes by. These findings showed that dietary intake, level of serum lipids and other vascular disease risk factors increased as BIM increased. Therefore, middle or upper class Korean adults who have high BMI should improve their eating habits. This involve reducing alcohol, animal fat, high carbohydrate foods, and overall food intake, and balancing intake in order to lower vascular disease risk factors, including obesity.