• Nutrition Research and Practice
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• v.17 no.6
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• pp.1099-1112
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• 2023

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

• Journal of Nutrition and Health
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• v.31 no.9
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• pp.1411-1421
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• 1998

The purpose of this study was to investigate the effects of apo E polymorphisms and dietary counseling on the levels of plasma lipids in hyperlipidemic patients. The changes of serum lipids were assessed f3r 34 hyperlipidemic out-patients who changed their basal diet containing 20.1% fat(236.0mg cholesterol/day), 15.7% protein, and 64.2% carbohydrate to a diet containing 18.3% fat(109.8mg cholesterol/day), 15.7% protein, and 66.0% carbohydrate for 12 weeks. At the beginning of this study, the levels of plasma LDL-cholesterol were high according to apo E genotypes in the following order : E2/3

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.110-114
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• 2004

Apolipoprotein E is the major lipid-carrier protein in the brain, and several studies provided evidence that apolipoprotein E(ApoE) epsilon4 allele can be considered a genetic risk factor for Alzheimer's disease(AD). Inheritance of the APOE gene has three alleles: ${\varepsilon}2$, ${\varepsilon}3$ and ${\varepsilon}4$. There are six possible genotypes: ${\varepsilon}2/{\varepsilon}2$, ${\varepsilon}3/{\varepsilon}3$, ${\varepsilon}4/{\varepsilon}4$, ${\varepsilon}2/{\varepsilon}3$, ${\varepsilon}2/{\varepsilon}4$, ${\varepsilon}3/{\varepsilon}4$. AD is characterized by a progressive loss of function and death of nerve cells in several areas of the brain. The ${\varepsilon}4$ allele is associated with a risk for developing AD. People with the ${\varepsilon}4/{\varepsilon}4$ genotype have the highest risk, but people with the ${\varepsilon}2/{\varepsilon}4$ or ${\varepsilon}3/{\varepsilon}4$ genotypes are also likely to develop the disease. 64.3% of people carry the is ${\varepsilon}3/{\varepsilon}3$ genotype, 22.1% carry the second ${\varepsilon}3/{\varepsilon}4$ genotype but, ${\varepsilon}2/{\varepsilon}2$ genotype is not usually found of people carry the 3.6% is ${\varepsilon}4/{\varepsilon}4$ genotype in a total of a test group of 140 people. The ratio of ${\varepsilon}4/{\varepsilon}4$ genotype related directly with AD is less than the ${\varepsilon}3/{\varepsilon}3$ genotype, but the ${\varepsilon}2/{\varepsilon}4$ and ${\varepsilon}3/{\varepsilon}4$ genotype ratio of indirect AD risk is 25.7% in the group of people, regardless. Thus, we have referred to the benefit from the treatment of AD through apoE genotype diagnosis.

• Korean Journal of Biological Psychiatry
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• v.27 no.2
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• pp.94-100
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• 2020

Objectives Amyloid β positron emission tomography (Aβ PET) is widely used as a diagnostic tool in patients who have symptoms of cognitive impairment, however, this diagnostic examination is too expensive. Thus, predicting the positivity of Aβ PET before patients undergo the examination is essential. We aimed to analyze clinical predictors of patients who underwent Aβ PET retrospectively, and to develop a predicting model of Aβ PET positivity. Methods 468 patients who underwent Aβ PET with cognitive impairment were recruited and their clinical indicators were analyzed retrospectively. We specified the primary outcome as Aβ PET positivity, and included variables such as age, sex, body mass index, diastolic blood pressure, systolic blood pressure, education, dementia family history, Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Box (CDR-SB), hypertension (HTN), diabetes mellitus (DM) and presence of apolipoprotein E (ApoE) E4 as potential predictors. We developed three final models of amyloid positivity prediction for total subjects, mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia using a multivariate stepwise logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) value was calculated for the ROC curve. Results Aβ PET negative patients were 49.6% (n = 232), and Aβ PET positive patients were 50.4% (n = 236). In the final model of all subjects, older age, female sex, presence of ApoE E4 and lower MMSE are associated with Aβ PET positivity. The AUC value was 0.296. In the final model of MCI subjects (n = 244), older age and presence of ApoE E4 are associated with Aβ PET positivity. The AUC value was 0.725. In the final model of AD subjects (n = 173), lower MMSE scores, the presence of ApoE E4 and history of HTN are associated with Aβ PET positivity. The AUC value was 0.681. Conclusions The cerebral amyloid positivity model, which was based on commonly available clinical indicators, can be useful for prediction of amyloid PET positivity in MCI or AD patients.

• BMB Reports
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• v.54 no.3
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• pp.170-175
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• 2021

Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA＋ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA＋ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.2
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• pp.236-244
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• 2006

This study was designed to determine the effects of daidzein (DE) on hepatic lipid metabolism in chicks fed with low protein (LP) diet based on casein. In experiment 1, the male chicks were fed with one of the three levels of dietary protein containing 10.95%, 21.9% and 43.8% protein content for 2 days. In experiment 2, the chicks were fed one of the three levels of protein with or without DE at 1,000 mg/kg diet for 2 days. Experiment 3 was conducted to compare DE (LP+DE) with estradiol (LP+E2) in chicks fed with LP diet for 7 days. Plasma lipid profiles, hepatic lipid profiles, activities of hepatic malic enzyme and isocitrate dehydrogenase (ICDH) were measured. Transcriptions of hepatic fatty acid synthase, apolipoprotein-B (APO-B), and fructose bisphosphatase mRNA were measured by RT-PCR. Increasing dietary protein levels markedly decreased the concentrations of plasma triglycerides, hepatic total lipids, hepatic TG, and the mRNA transcriptions while the increased dietary protein levels increased hepatic ICDH activities in experiment 1. In experiment 2, the effects of dietary protein levels on blood and hepatic lipid content were more prominent than those of the additional DE. Interestingly, plasma TG levels were affected by DE supplementation (p<0.05). In experiment 3, DE inhibited APO-B mRNA expressions and stimulated the accumulation of lipid in the liver through mechanisms different from E2. In this study, we demonstrate that DE has beneficial effects on blood lipid profiles, but that it inhibits APO-B mRNA transcription and aggravates the fatty liver induced by LP diet in chicks.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1071-1079
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• 2006

The purpose of this study was to observe the effects of the feeding physiological activity substance in feral peach(Prunus Persica Batsch var. davidiana Max.) extract intake on the improvement of the lipid compositions, apolipoprotein and blood pressure level in spontaneously hypertensive rats(SHR, Wistar strain, male) fed the experimental diets for 33 days. Concentrations of total cholesterol, triglyceride(TG), LDL-cholesterol, free cholesterol and atherosclerotic index in serum were significantly lower in the feral peach extract intake groups[groups 5g% Ex.(basal diet+feral peach 5.0g% extract), 10g% Ex.(basal diet+feral peach 10.0g% extract)] than those in the group Control(basal diet+water). In the ratio of HDL-cholesterol concentration to total cholesterol and HDL-cholesterol concentration, feral peach 5.0g%, 10.0g% extract intake groups(group 5g% Ex. and 10g% Ex.) were higher percentage than in the group Control. However, concentrations of total cholesterol and TC in liver and brain were significantly lower in the groups 5g% Ex. and 10g% Ex. than those in the group Control. But the concentrations of apolipoprotein (Apo) A-I and Apo A-II in serum were significantly higher in the feral peach 5.0g% and 10.0g% extract intake groups(5g% Ex. and 10g% Ex.) than in the control group. However, concentrations of Apo C-II, Apo C-III, Apo E and ratio of Apo B to Apo A-I in serum were fairly reduced in the groups 5g% Ex. and 10g% Ex. than in the control group. The levels of systolic and diastolic blood pressure were significantly lower in feral peach 5g% Ex. and 10g% Ex. groups than control group. However, no significance was found in the effect of among the groups(groups 5g% Ex. and 10g% Ex.). From these results, physiological activity substance in feral peach(Prunus persica Batsch var. davidiana Max.) extracts were effective on the improvement of the lipid compositions and cardiovascular heart disease, hypertension in spontaneously hypertensive rats. And particularly, feral peach extracts were more effective as a therapeutic regimen for the control of blood pressure in hypertension.

• Proceedings of the KSAR Conference
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• 2002.06a
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• pp.82-82
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• 2002

The Wnt signaling pathway plays pivotal roles in embryonic development and oncogenesis through various signaling molecules inculding Frizzled receptor, recently characterized LRP5/6 and Dickkopf protein. Although Wnt signaling has been characterized in both developmental and oncogenic processes, little is known about its function in the normal adult. The ability of LRP5 to bind apolipoprotein E(apoE) and the abundant expression of LRP5 transcripts in hepatocytes, raise the possibility that LRP5 plays a role in the hepatic clearance of ApoE-containing chylomicron remonants, a major plasma lipoprotein carrying diet-derived cholesterol. (omitted)

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.161-170
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• 2017

Background: There is recent evidence that insulin resistance is responsible for increasing the risk of developing cognitive dysfunction. To systematically review the influence of intranasal insulin treatment on the cognitive function in Alzheimer's disease patients. Methods: Randomized controlled trials comparing the cognitive effects of intranasal insulin therapy in Alzheimer's disease patients with controlled interventions were retrieved from Pubmed, Medline, Embase and Cochrane library. Meta-analysis was conducted on the cognitive measurements with a subgroup analysis by dose, gender and apolipoprotein E allele 4 (ApoE ${\varepsilon}4$) status. Results: Seven randomized controlled trials were eligible for inclusion. Intranasal insulin had a positive influence on the cognitive function as compared to placebo without a statistical significance (standardized mean difference; SMD = 0.109; 95% confidence interval; CI -0.04 to 0.26; P=0.14). In subgroup analysis, a 20 IU dose of intranasal insulin induced a significant improvement in cognitive function (SMD = 0.14; 95% CI 0.05 to 0.24; P=0.004), but 40 IU did not show this effect (SMD = -0.01; 95% CI -0.11 to 0.09; P=0.82). ApoE ${\varepsilon}4$ positive patients showed a significant decline in cognitive function as compared to ApoE ${\varepsilon}4$ positive patients in the control group (SMD = -0.213; 95% CI -0.38 to -0.04; P=0.015). Such an effect was not apparent in ApoE ${\varepsilon}4$ negative patients. Gender had no influence on the cognitive outcomes. Conclusion: The results indicate that intranasal insulin may have beneficial effect in improving the cognitive function in Alzheimer's disease patients.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.