• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.8
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• pp.477-484
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• 2019

Several types of scavenger receptors, including the Collectin-Placenta 1 (CL-P1) receptorthat is present in mammals, are molecules that are expressed on the surfaces of endothelial cells, macrophages and smooth muscle cells. These molecules are cell surface glycoproteins that can be conjugated to oxidized low density lipoprotein (oxLDL). Among these molecules, the effect of quercetin on CL-P1 activation has been confirmed. Quercetin is known as an antioxidant that stops oxidation because it acts to remove free radicals that are responsible for the oxidation reaction. In this study, fragments from the transcription start site of the mouse CL-P1 gene promoter to the -500th base were cloned using DNA polymerase. These fragments were then introduced into macrophage like RAW264.7 cells and fibroblast-like NIH3T3 cells to study the effect of quercetin on the CL-P1 gene expression. As a result, we found that bases ranging from -250 to -350 in the anterior part where gene expression starts are important for producing CL-P1 protein. Among them, the DNA mutation experiments we performed confirmed that the E2F binding sites are critical for producing the CL-P1 protein? In addition, when quercetin was added to the RAW264.7 culture medium, which was a culture of adherent cells, observedthe phenomenon of the cells falling off from the surface of the culture container.

• Korean Journal of Food Science and Technology
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• v.51 no.3
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• pp.272-277
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• 2019

The effects of medium-chain enriched diacylglycerol (MCE-DAG) oil on hepatic cholesterol homeostasis were investigated. HepG2 hepatocytes were treated with either 0.5, 1.0, or $1.5{\mu}g/mL$ of MCE-DAG for 48 h. There was no evidence of cytotoxicity by MCE-DAG up to $1.5{\mu}g/mL$. The level of proteins for cholesterol uptake including CLATHRIN and LDL receptor increased by MCE-DAG in a dose-dependent manner (p<0.05). Furthermore, proprotein convertase subtilisin/kexin type 9, an inhibitor of LDLR, was dose-dependently diminished (p<0.05), indicating cholesterol clearance raised. MCE-DAG significantly increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acetyl-CoA acetyltransferase2 (p<0.05), required for cholesterol synthesis, and their transcriptional regulator sterol regulatory element-binding protein2 (p<0.05). These findings suggest that given conditions of prolonged sterol fasting in the current study activated both hepatic cholesterol synthesis and clearance by MCE-DAG. However, total intracellular level of cholesterol was not altered by MCE-DAG. Taken together, MCE-DAG has the potential to prevent hypercholesterolemia by increasing hepatic cholesterol uptake without affecting intracellular cholesterol level.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.81-93
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• 2021

Objectives The objective of the study was to investigate effects of ChondroT by improvement of blood metabolites in high-fat diet (HFD)-induced hyperlipidemia rat model. Methods Sprague-Dawley rats were randomly assigned to intact, control, simvastatin, and CT100, CT200 and CT400 (each n=6). For observing cholesterol change, animals were first fed high fat diet for 5 weeks and then high fat diet and drugs for 3 weeks. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were analyzed by obtained blood collection. Further, amplified leptin, peroxisome proliferator activated receptor (PPAR) and adiponectin DNA were observed by reverse transcription polymerase chain reaction analysis. Results Observing the effect of ChondroT on the change of lipid metabolism in hyperlipidemia-induced rats, triglyceride and total cholesterol were significantly decreased in SV100 group, HDL-C was significantly increased in SV100, CT100 and CT200 groups, and LDL-C was significantly decreased in SV100, CT100, CT200 and CT400 groups, compared to the control group. Leptin level in hyperlipidemia-induced rats was significantly decreased in CT100 and CT200 groups, compared to the control group. The effect of ChondroT on adiponectin level in hyperlipidemia-induced rats was significantly increased in SV100, CT100 and CT200 groups. PPAR level in hyperlipidemia-induced rats was significantly decreased in SV100, CT200 and CT400 groups. Platelete activating factor level in hyperlipidemia-induced rats was significantly decreased in CT100 and CT200 groups. Conclusions Based on these results, it could be suggested that ChondroT has certain effects of improving blood metabolites in HFD-induced hyperlipidemia.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.2
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• pp.102-114
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• 2022

Objectives: We investigated the effects of Allii Fistulosi Bulbus (AFB) on high fat diet (HFD)-induced obesity in mice and the regulation of energy metabolism in muscle tissues of mice. Methods: The C57BL/6 mice (6 weeks, male) were fed a HFD for 8 weeks and then administrated with AFB extract at 500 mg/kg (p.o.) once daily for 4 weeks. The body weight (BW), muscle weight, calorie intake, fasting blood glucose (FBG) and serum glucose, insulin, and low-density lipoprotein-cholesterol (LDL-C) levels were measured in mice. It was also observed the histological changes of pancreas, liver, and fat tissues with hematoxylin and eosin staining. It was investigated the phosphorylation of insulin receptor substrate 1 (IRS-1), Ser/Thr kinase (AKT), and adenosine monophosphate-activated protein kinase (AMPK), and the expression of phosphoinositide 3-kinase, glucose transporter type 4 (GLUT4), and sirtuin1 (Sirt1) in gastrocnemius tissues by western blot, respectively. Results: The increases of BWs, calorie intakes and FBG levels in obesity mice were decreased significantly by the administration of AFB extract. The AFB extract administration was reduced significantly serum levels of glucose, insulin, and LDL-C in obesity mice. The AFB extract inhibited lipid accumulation in liver tissues, hyperplasia of pancreatic islets, and enlargement of fat tissues in obesity mice. The phosphorylation of IRS-1 and AKT was increased significantly in muscle tissues and AMPK phosphorylation and the GLUT4 and Sirt1 expression were decreased significantly in muscle tissues after the AFB administration. Conclusions: Our study indicates that AFB extract improves symptoms of obesity through regulation of energy regulating proteins in muscle tissues.

• Journal of Life Science
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• v.33 no.12
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• pp.967-977
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• 2023

Rubus crataegifolius (RC) is a traditional Asian medicinal plant belonging to the Rosaceae family. The fruits of RC are known to prevent adult diseases through antioxidants. In this study, the effects of RC extract (RCex) on obesity and nonalcoholic fatty liver disease (NAFLD) were evaluated in animal models. Twenty-eight male C57BL/6J mice were induced to become obese for 8 weeks and then the extract was orally administered for 8 weeks. RCex reduced body weight, adipose tissue, liver weight. RCex improved biochemical biomarkers including lipid metabolism (alanine aminotransferase (ALT), aspartate aminotransferase (AST), plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol). The activation of AMP-activated protein kinase (AMPK) reduced the expression of adipogenesis genes (liver × receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthesis (FAS), acetyl-CoA carboxylase 1 (ACC1) and the effect of enhancing carnitine palmitoyltransferase (CPT) activity by RCex was verified. RCex also influence on plasma production of hormones (adiponectin & leptin) related on energy expenditure and metabolism. In addition, we confirmed that RCex improved glucose intolerance in HFD-induced obese rats. RCex was first demonstrated to have anti-obesity as well as anti-NAFLD effects by regulating fatty acid oxidation and fatty acid synthesis by phosphorylation of AMPK. This suggests that RCex could be a good supplement for the prevention of obesity and related NAFLD.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.77-81
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• 2010

Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR $\alpha$), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.

• 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.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.871-886
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• 2008

Objective : Gypsum fibrosum has been traditionally used in treatment of febrile diseases and recently been shown to have anti-inflammatory effect. Chronic renal failure has a serious clinical symptoms including proteinuria, azotemia, anemia, and hyperlipidemia and has characteristic histopathological changes, glomerular hypertrophy, infiltration of inflammatory cells, and crescentic sclerosis, We investigated the effects of gypsum fibrosum on renal functional and histopathological disorder in chronic renal failure rat model induced 5/6 nephrectomy. Methods : Using Sprague-Dawley rats, CRF was induced by 5/6 nephrectomy. The rats were divided into 3 groups, normal, conrol, and gypsum administered orally with gypsum fibrosum 500mg/kg/day. Body weight, 24 hr proteinuria, hematologic analysis, and histological morphologic changes were followed up after 8 weeks. The glomerular macrophage/monocyte infiltration, $TGF-{\beta}_1$, type IV collagen, and angiotensin II type1 receptor($AT_1$) were evaluated by immunohistochemistry. Resuls : In the CRF control group, functional parameters and histopathologic changes clearly indicated the development of CRF. 24 hr proteinuria significantly increased in the CRF control group over the normal group, and serum creatinine level was lower in the gypsum group than in the control group, LDL-cholesterol was significantly lower in the gypsum group than in the control group. Morphological investigations showed a variety of characteristic features of CRF, glomerular hypertrophy, increasing cellular density of glomerulus, deposition of extra-cellular matrix, fibrotic change, and glomerular sclerosis in the control group, but in the gypsum group, these features diminished significantly. In observation of renal type IV collagen and $AT_1$ expression, positive area significantly increased in the control group over the normal group, and it significantly decreased in the gypsum group compared to the control group. Conclusions : Our findings suggest that gypsum fibrosum inhibits $AT_1$ and type IV collagen expression in renal tissues and attenuates progression of glomerulosclerosis and interstitial fibrosis in chronic renal failure rats, which lead to amelioration of renal function. From these results, we suggest that gypsum fibrosum may have renoprotective effects and could be a useful remedy agent for treating chronic renal failure.

• The Journal of Internal Korean Medicine
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• v.35 no.4
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• pp.519-531
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• 2014

Objectives: Diabetic nephropathy is the most common cause of end stage renal disease. Transforming growth factor (TGF)-${\beta}1$, type IV collagen, advanced glycation end-products (AGEs), and angiotensin II type 1 receptor (AT1) are the main factors of diabetic nephropathy. We investigated the effects of Prunus on renal function and histopathological changes of diabetic nephropathy rat model induced by unilateral nephrectomy and streptozotocin. Methods: Diabetes was induced in male Sprague-Dawley rats ($290{\pm}10g$) by injecting streptozotocin (55 mg/kg) into the tail vein after unilateral nephrectomy. Rats were divided into 3 groups (n=6): normal, control, and Prunus. After 8 weeks of oral administration of Prunus extract on the Prunus group from 3 days after streptozotocin injection, we checked weight, 24 hrs urine, blood biochemistry and renal tissue to evaluate renal function and histopathological changes by examining parameters including albuminuria, BUN, creatinine, cholesterol, low density lipoprotein (LDL), triglyceride, TGF-${\beta}1$, type IV collagen, AGEs, and AT1. We also measured mRNA expression of TGF-${\beta}1$, type IV collagen, AGEs, and AT1 by Real Time polymerase chain reaction (RT-PCR). Results: Prunus decreased the amount of 24 hrs proteinuria, and inhibited histopathological changes of diabetic nephropathy including the expression and accumulation of TGF-${\beta}1$, type IV collagen and AGEs which could promote development of diabetic nephropathy. Prunus also inhibited mRNA expression of TGF-${\beta}1$, type IV collagen. Conclusions: These findings suggest that Prunus might protect the renal function and inhibit the development of renal injury by regulating factors including TGF-${\beta}1$, type IV collagen, AGEs, except AT1, so Prunus can be used for diabetic patients to prevent the progression of diabetic nephropathy.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.198-205
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• 2017

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.