• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.1
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• pp.73-78
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• 2012

Excessive intake of trans fats is known to be a risk factor for cardiovascular diseases. Previously, we have shown that green tea extract (GTE) lowers the intestinal absorption of lipids and lipid-soluble compounds in rats. This study was conducted to investigate a possible role of GTE on the lymphatic absorption of elaidic acid, a major trans fat in the diet. Adult male Sprague-Dawley rats with lymph duct cannula were infused via an intraduodenal catheter at 3.0 mL/hr for 8 hr with a lipid emulsion containing $180.0{\mu}mol$ elaidic acid, $400.0{\mu}mol$ triolein, $20.7{\mu}mol$ cholesterol, $3.1{\mu}mol$ ${\alpha}$-tocopherol, and $396.0{\mu}mol$ sodium-taurocholate with or without (control) GTE in a 24 mL PBS buffer (pH, 6.4). Simultaneously, lymph was collected hourly for 8 hr via the lymph duct cannula. There was a significant difference in lymph flow by GTE. Also, the lymphatic absorption of elaidic acid for 8 hr was significantly lower in rats infused with GTE than in those not infused with GTE. Similarly, GTE infusion decreased the lymphatic outputs of cholesterol, oleic acid, and phospholipids, compared with the controls. These findings provide clear evidence that GTE has an inhibitory effect on the intestinal absorption of elaidic acid and other lipids. Our work here provides the foundation for further studies to examine and evaluate dietary strategies to ameliorate dietary trans fats from the diet.

• BMB Reports
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• v.51 no.5
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• pp.255-260
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• 2018

Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• Korean Journal of Pharmacognosy
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• v.36 no.4 s.143
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• pp.318-323
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• 2005

The leaves (KPL) of Kalopanax pictus (KP) are used as a vegetable or a functional food in Korean society. The stem bark (Kalopanacis Cortex, KPS) has been traditionally used to treat neurotic pain, rheumatoid arthritis and diabetic disease. This research was undertaken to demonstrate that the leaf extract of KP (KPL) has also the antinociceptive and antiinflammatory effects like the extract (KPS) of Kalopanacis Cortex and to compare the activity levels of several extracts obtained from KP. Antinociceptive and antiinflammatory effects were measured against the extracts described as followings; KPL-1 (the MeOH extract obtained from the leaf shoot of KP collected on May), KPL-2 (the MeOH extract from KP collected on June), KPL-3 (the MeOH ectract from KP with no thorns), KPS-1 (MeOH extract from KPS of a Korean habitat), KPS-2 (MeOH extract from KPS of a Chinese habitat). The antimociceptive test undertaken by acetic acid-induced writhing, hot plate-, and tail-flick methods using mice. The anti-inflammatory test was also undertaken by measuring the edema in the carrageenan-induced test. The order of activity potency in the antinociceptive and antiinflammatory assays was commonly shown as followings: KPL-3>KPS>1>KPS-2>KPL-1>KPL-2. This order was also observed in acetic acid-induced vascular permeability test. The antiinflammatory activity in carrageenan-induced assay was also observed as the following order: KPL-3>KPS- 1>PS-2>KPL-1>KPL-2. In addition, adjuvant-induced rats were used for a model to assess the oxidative stress. Treatment of the rat with the extracts reduced serum thiobarbituric acid-reactive substances (TBARS), hydroxy radical(OH) and superoxide dismutase(SOD) activity caused by FCA together together with the inhibition of hepatic TBARS level and lipofuscin content. The above finding suggests that the leaf extract has the antinociceptive and antinflammatory activity. It is also suggested that KPL-3 with more potent activity than other tested extracts could be developed for a new available biomaterial.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.462-470
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• 2012

Mountain cultivated ginseng (MCG) is a type of Panax ginseng C. A. Mayer, grown in the mountains by artificial seeding. In general, it has been known that the biophysical activities of MCG is greater than that of ginseng. However, the in vivo efficacy of MCG on cancer has not been studied. In this study, we investigated the anti-carcinogenic effect of MCG and ginseng using the 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanoylphorbol- 13-acetate (TPA) two stage mouse skin carcinogenesis model. Six weeks of female ICR mice were divided into control, MCG, and ginseng diet groups and were subjected into two different experimental protocols. In the first study, each experimental diet was fed with TPA promotion for 24 weeks. The result showed that supplementation of MCG reduced tumor incidence, tumor multiplicity, and tumor size compared to those of the control and ginseng groups. In the second study, 3 groups of mice were supplied with each diet 4 weeks before DMBA tumor initiation, until the end of experiment. The result showed that tumor incidence, tumor multiplicity, and tumor size were reduced in the ginseng diet group compared to those of the control and MCG groups. TPA-induced BrdU incorporation was also significantly reduced in the ginseng diet group. Taken together, these results suggest that MCG is chemotherapeutic, whereas ginseng has a chemopreventative effect on mouse skin cancer.

• Journal of Life Science
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• v.20 no.7
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• pp.969-976
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• 2010

In vivo studies of KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) were performed in pithed rats, conscious angiotensin II (AII) challenged normotensive rats, renal hypertensive rats (RHRs) and furosemide-treated beagle dogs. KR-31125 induced a non-parallel right shift in the dose-pressor response curve to AII ($ID_{50}$: 0.095 mg/kg) with a dose-dependent reduction in the maximum responses in pithed rats. Compared to losartan, this antagonistic effect was about 18 times more potent, presenting competitive antagonism. Other agonists such as norepinephrine and vasopressin did not alter the responses induced by KR-31125. Orally administered KR-31125 had no agonistic effect and dose-dependently inhibited the pressor response to AII with a slightly weaker potency ($ID_{50}$: 0.25 and 0.47 mg/kg, respectively) in the AII-challenged normotensive rat model, but with a more rapid onset of action than losartan (time to $E_{max}$: 30 min for KR-31125 and 6 hr for losartan). KR-31125 produced a dose-dependent antihypertensive effect with a higher potency than losartan in RHRs, and these effects were confirmed in furosemide-treated dogs where they presented a dose-dependent and long-lasting (>8 hr) antihypertensive effect with a rapid onset of action (time to $E_{max}$: 2-4 hr), as well as a 20-fold greater potency than losartan. These results suggest that KR-31125 is a potent, orally active $AT_1$ receptor antagonist that can be applied to the development of new diagnostic and research tools as an added exploratory potential of $AT_1$ receptor antagonist.

• Journal of Microbiology and Biotechnology
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• v.26 no.6
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• pp.1140-1147
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• 2016

The plasma and serum of Crocodylus siamensis have previously been reported to exhibit potent antimicrobial, antioxidant, and anti-inflammatory activities. During wound healing, these biological properties play a crucial role for supporting the formation of new tissue around the injured skin in the recovery process. Thus, this study aimed to evaluate the wound healing properties of C. siamensis plasma and serum. The collected data demonstrate that crocodile plasma and serum were able to activate in vitro proliferation and migration of HaCaT, a human keratinocyte cell line, which represents an essential phase in the wound healing process. With respect to investigating cell migration, a scratch wound experiment was performed which revealed the ability of plasma and serum to decrease the gap of wounds in a dose-dependent manner. Consistent with the in vitro results, remarkably enhanced wound repair was also observed in a mouse excisional skin wound model after treatment with plasma or serum. The effects of C. siamensis plasma and serum on wound healing were further elucidated by treating wound infections by Staphylococcus aureus ATCC 25923 on mice skin coupled with a histological method. The results indicate that crocodile plasma and serum promote the prevention of wound infection and boost the re-epithelialization necessary for the formation of new skin. Therefore, this work represents the first study to demonstrate the efficiency of C. siamensis plasma and serum with respect to their wound healing properties and strongly supports the utilization of C. siamensis plasma and serum as therapeutic products for injured skin treatment.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.2
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• pp.76-83
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• 2006

Epidemiological studies have indicated that the ubiquitous consumption of seaweeds is a protective factor against some types of cancer. Previous results showed that the administration of seaweed powder or extract reduced the incidence rate of chemically induced tumorigenesis using in vivo animal model. Recently, we reported that the extracts of Gloiopeltis furcata, a kind of Korean edible seaweed, caused he cell growth inhibition of various human cancer cell lines, among them methanol extract exhibited a relatively strong antiproliferative activity. However, the molecular mechanisms of this seaweed in malignant cells have been poorly studied until now. To elucidate this problem, we investigated the effects of methanol extract of G. furcata (MEGF) on the growth inhibition in several human cancer cell lines, and further we analyzed the effects of this extract were tested on the activity of apoptosis induction in human leukemic cells. The results demonstrated that MEGF treatment resulted in the morphological changes and the growth inhibition in a dose-dependent manner. Furthermore, MEGF potently suppresses the growth of human leukemic U937 cells by induction of apoptosis, which was associated with induction of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in a tumor suppressor p53-independent fashion and up-regulation of Fas/FasL system. Further studies will be needed to identify the active compounds that confer the anticancer activity of MEGF. Once such compounds are identified, the mechanisms by which they exert their effects can begin to be characterized.

• Molecules and Cells
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• v.27 no.1
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• pp.105-111
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• 2009

Gammaherpesvirus infection of the central nervous system (CNS) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. However, little is known about the interactions between the virus and the CNS in vitro or in vivo. Murine gammaherpesvirus 68 (MHV-68 or ${\gamma}HV-68$) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and replication. In the present study, we show the successful infection of cultured neuronal cells, microglia, and astrocytes with MHV-68 to various extents. Upon intracerebroventricular injection of a recombinant virus (MHV-68/LacZ) into 4-5-week-old and 9-10-week-old mice, the 4-5-week-old mice displayed high mortality within 5-7 days, while the majority of the 9-10-week-old mice survived until the end of the experimental period. Until a peak at 3-4 days post-infection, viral DNA replication and gene expression were similar in the brains of both mouse groups, but only the 9-10-week-old mice were able to subdue viral DNA replication and gene expression after 5 days post-infection. Pro-inflammatory cytokine mRNAs of tumor necrosis factor-${\alpha}$, interleukin $1{\beta}$, and interleukin 6 were highly induced in the brains of the 4-5-week-old mice, suggesting their possible contributions as neurotoxic factors in the age-dependent control of MHV-68 replication of the CNS.

• Korean Journal of Food Science and Technology
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• v.48 no.4
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• pp.384-391
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• 2016

In previous studies, we confirmed that the ethanol extract of Polygonatum sibiricum (ID1216) has anti-obesity effects on high-fat diet-fed mice. To identify the obesity-related genes affected by ID1216, we studied its effects both in vivo and in vitro. In mice, single administration of ID1216 increased the expression of obesity-related genes including sirtuin1 (SIRT1), peroxisome proliferator-activated receptor ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$) and peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) compared to that in mice administered the vehicle; their downstream genes (uncoupling proteins, acyl-CoA oxidase, adipocyte protein 2, and hormone-sensitive lipase) were also increased by ID1216. In fully differentiated 3T3-L1 adipocytes, ID1216 showed the same effects on anti-obesity genes as those in the animal model. Based on these results, we propose that ID1216 has anti-obesity effects by regulating the $SIRT1-PGC1{\alpha}-PPAR{\alpha}$ pathway and their downstream genes, thereby controlling energy and lipid metabolisms.