• Journal of Ginseng Research
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• 제37권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5403-5408
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• 2013

Objective: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. Methods: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. Results: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP-9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). Conclusions: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.

• Nutrition Research and Practice
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• 제15권4호
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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.

• 대한본초학회지
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• 제28권4호
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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.

• Biomolecules & Therapeutics
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• 제31권1호
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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.

• Journal of Ginseng Research
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• 제27권3호
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• pp.110-114
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• 2003

Objective; Antistress effect of Korean red ginseng (RG) on postmenopausal women with severe climacteric syndrome (CS) were evaluated from the viewpoint of traditional KAMPO-medicine and Western medicine. Methods; All patients with CS were treated with daily oral administration of 6g RG for 30 days. Nine patients with CS were evaluated with the use of diagnostic scores for KI-deficiency (deficiency of vital energy) and OKETSU (blood stagnation) syndrome from the viewpoint of KAMPO-medicine. In the same patients with CS, peripheral blood levels of ${\beta}$-endorphin and total plasminogen activator inhibitor-1 (t-PAI-1) were measured before and after treatment with RG. In another group, 12 patients with CS, psychological test using CMI, STAI and SDS were performed from the viewpoint of Western medicine. Stress related hormones, such as ACTH, cortisol and DHEA-S in those 12 patients with CS were also measured before and after treatment with RG. Results; KI-deficiency score and OKETSU score in patients with CS were significantly (p<0.001) higher than those in patients without CS. After treatment with RG, both scores were markedly (p<0.001) decreased compared to before treatment with RG. ${\beta}$-endorphin levels in patients with CS were significantly (p<0.05) higher than those in patients without CS. Total PAI-levels in patients with CS were increased before treatment with RG. No significant difference, however, were observed between patients with and without CS. After treatment with RG, both levels of ${\beta}$-endorphin and total PAI-1 in patients with CS were significantly (p<0.001 and p<0.05, respectively) decreased compared to before treatment with RG. CMI and STAI scores in patients with CS were significantly (p<0.05) higher than those in patients without CS. SDS scores in patients with CS were also markedly (p<0.00l) higher than in those without CS. After treatment with RG, all scores decreased within normal range. DHEA-S levels in patients with CS were about a half of those without CS. Consequently, cortisol/DHEA-S (C/D) ratio was significantly(p<0.001) higher in patients with CS than in those without CS. Although the decreased DHEA-S levels were not restored to the levels in patients without CS, the C/D ratio decreased significantly (p<0.05) after treatment with RG. Conclusion; Reinforcement of vital energy and improvement of stagnant blood circulations by oral administration of RG were elucidated from the viewpoint of traditional KAMPO-medicine. From the viewpoint of Western medicine, effect of RG on postmenopsusal women with CS seemed to be brought about in part by not only an improvement of psychoneuroendocrine dysfunctions but also an amelioration of blood coagulation systems.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• 대한지역사회영양학회지
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• 제6권1호
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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.

• Nutritional Sciences
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• 제1권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4067-4073
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• 2012

Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator activated receptor$receptor{\gamma}$ ($PPAR{\gamma}$) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-$A^{\mathcal{Y}}$ obesity and diabetes model mice, and tried to clarify mechanisms by which the $PPAR{\gamma}$ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF/mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-$A^{\mathcal{Y}}$ mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.