• Nutrition Research and Practice
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• 제17권6호
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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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• 제31권9호
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• pp.1411-1421
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• 1998

본 연구에서는 경희의료원 내과에 내원하고 있는 고지혈증 환자를 대상으로 12주 동안 영양상담을 통하여 식사조절을 실시하였으며. 이들 환자들의 apo E 유전자 다형성의 분포양상을 조사하였다 또한 그들의 식습관 분석과 더불어 영양상담 및 교육에 의한 식사조절이 apo E 유전자 다형성에 따라 혈중 지질 농도에 미치는 효과를 관찰함으로써, apo E 유전자 다형성과 식사 조절 후 혈청 지질 농도와의 상호 연관성을 조사하여 다음과 같은 결과를 얻었다. 1) 고지혈증 환자의 apo E 유전자 다형성의 분포양상을 살펴보면 apo E3/3가 70.6% . apo E3/4가 23.5%. 그리고 apo E2/3가 5.8%의 분포를 나타냈다. 일반적 특성인 연령, 몸무게, BMI, %IBW, WHR. 그리고 혈압에서는 apo E 유전자형에 따른 차이가 나타나지 않았으나 12주의 식사조절 후 모든 환자들에서 몸무게, BMI, %IBW, WHR, 그리고 혈압 감소의 경향을 보였다. 2) 고지혈증 환자가 평소 섭취하고 있는 식사 종류는 밥과 면류, 국류, 나물 및 무침류, 구이 및 조림류, 전류 및 볶음요리, 찌게류로 조사되었다. 3) 고지혈증 환자는 영양상담 후 포화지방과 콜레스테롤이 많은 음식의 섭취빈도가 감소하였고, 짠 음식 중 알, 젓갈류의 섭취가 감소하였다. 단음식과 인스턴트 식품의 섭취빈도도 감소하였다. 튀긴음식 섭취와 간식의 빈도도 감소하여 고지혈증 환자를 대상으로 실시한 12주간의 영양상담은 환자들의 식습관과 식품섭취 개선에 좋은 효과를 보였다. 4) 고지혈증 환자의 영양상담 전 식사는 탄수화물 : 단백질 : 지방의 비율이 64.2 : 15.7 : 20.1이었던 반면, 상담 후에는 그 비율이 66.0 : 15.7 : 18.3으로 지방의 섭취비율이 다소 낮아졌다. 또한 영양상담 이전의 콜레스테를 섭취는 236.0mg/day이었으며, 상담 후에는 109.8mg/day로 섭취량이 감소하였다. 5) 영양상담 전의 혈청 LDL-콜레스테롤은 apo E3/4군에서 164.2m조dl, E3/3군에서 133.4mg/dl 그리고 E2/3군에서 112.2mg/dl로 apo E3/4군에서 가장 높았고, 그 다음이 E3/3, 그리고 E2/3의 순으로 나타났으며 , 상담 후 apo E3/4에서 가장 많이 감소하였다. (13.3%) 영양상담 후. 혈청 총 콜레스테롤은 ape E3/4에서 15.6%, E3/3에서 8.5% 감소하였다(p<0.01). 혈청 중성지방과 VLDL-콜레스테를 수준도 모든 군에서 감소하였으며, 특히 3/3군에서 유의성있게 감소하였다. 그러나 HDL-콜레스테를 농도에는 각 군간에 차이없이 증가하는 양상을 보였다. Apo E3/4환자들에서 총 콜레스테롤과 LDL-콜레스테롤이 가장 크게 감소하여 식사조절의 효과가 가장 높은 것으로 나타났다. 6) Apo E 유전자 다형성에 따른 고지혈증환자에서 BMI의 감소량이 클수록 혈청 총 콜레스테를 수준이 비례적으로 감소하였지만(r=0.373, p<0.05), 혈청 중성지방과의 상관관계는 나타나지 않았다. 또한 포화지방의 섭취량이 감소함에 따라 혈청 콜레스테롤농도가 유의적으로 감소하였다(r=0.900, p<0.01).

• 대한임상검사과학회지
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• 제36권2호
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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.

• 생물정신의학
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• 제27권2호
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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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• 제54권3호
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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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• 제19권2호
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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.

• 생명과학회지
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• 제16권7호
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• pp.1071-1079
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• 2006

야생 돌복숭아(Prunus persica Batsch var. davidiana Max.)의 생리활성 추출물질이 선천성 고혈압 흰쥐(SHR)의 지질대사 이상 및 고혈압 예방과 개선효과 등에 생리생화학적 효능이 있을 것으로 추정되어 Wistar 계 수컷 SHR을 사용하여, 기본식이와 물만을 급여한 대조군인 Control군과 SHR에 돌복숭아 5.0g% 추출액을 급여한 군(5g% Ex.군) 및 SHR에 돌복숭아 10.0g% 추출액을 섭취시킨 10g% Ex.군을 33일간 실험 사육하여 혈청 지질성분 및 혈압 저하 효과를 생리적 측면에서 검토하기 위하여 본 실험을 수행하였다. 혈청 중의 총 콜레스테롤 농도, 중성지방, LDL-콜레스테롤, 유리 콜레스테롤 및 동맥경화지수 등에서 돌복숭아 생리활성물질 5.0g%, 10.0g% 추출액을 섭취시킴으로서 유의적인 농도 등의 감소 효과를 보였으며, HDL-콜레스테롤 농도 및 총 콜레스테롤에 대한 HDL-콜레스테롤 비는 상승되는 것으로 나타났다. 한편, 간장 및 뇌 중의 총 콜레스테롤, 중성지방 농도는 돌복숭아 5.0g%, 10.0g% 추출액을 섭취시킨 군에서 감소되는 것으로 나타났다. 반면, 혈청 apolipoprotein(Apo) A-I, Apo A-II 농도 등은 돌복숭아 5.0g%, 10.0g% 추출액을 섭취시킨 군에서 유의적으로 증가되는 것으로 나타났다. 또한 Apo C-II, Apo C-III, Apo E 및 Apo A-I에 대한 Apo B의 농도 비는 감소되었으며, 혈압의 변화는 SHR에 돌복숭아 5.0g% 및 10.0g% 추출액을 섭취시킴으로서 혈압이 저하됨을 관찰할 수가 있었다. 돌복숭아 5.0g% 농도(5g% Ex.군)와 10.0g% 농도(10g% Ex.군)의 추출액 섭취에 따른 두 군간에 각종 지질성분과 apolipoprotein 분획 농도 및 혈압 변화의 비교는 유의적인 차이는 없었다 따라서 야생 돌복숭아 중의 생리활성물질 추출액 섭취가 선천성 고혈압 흰쥐에 대한 혈청 지질개선 및 심장순환기계 질환, 고혈압의 예방과 치료개선에 효과가 있을 것으로 생각된다.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2002년도 춘계학술발표대회 발표논문초록집
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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)

• 한국임상약학회지
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• 제27권3호
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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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• 제79권3호
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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.