• 한국식품과학회지
• /
• 제42권2호
• /
• pp.210-216
• /
• 2010

혈당강하 효과가 있다고 알려진 해당근 추출물을 이용하여 AGEs 생성 저해에 따른 초기 동맥경화증에 대한 효과에 대하여 검토하였다. 먼저 해당근 추출물이 AGEs에 의하여 생성이 촉진된 ROS를 제거하는 효과가 있는지를 확인하기 위하여 항산화 활성을 측정하였다. 총 플라보노이드 함량을 측정한 결과 해당근의 메탄올 추출물은 $128.1{\pm}2.0\;{\mu}g$ quercetin equivalents(QE)/mg DM,총 폴리페놀 함량은 $345.2{\pm}5.7\;{\mu}g$ gallic acid equivalents(GAE)/mg DM으로 나타났다. 환원력 측정을 위한 FRAP assay는 $2.19{\pm}0.1\;mM$ $FeSO_4{\cdot}7H_2O$/mg DM으로 $25.5{\pm}0.3$ $FeSO_4{\cdot}7H_2O$/mg DM 인 ascorbic acid에 비해 약 9% 정도의 환원력을 가지고 있었으며, 전자공여능의 경우 $DPPHSC_{50}$값이 $34.2{\pm}0.1\;{\mu}g$ DM/mL로 대조군인 ascorbic acid의 $6.8{\pm}0.1\;{\mu}g$ DM/mL과 비교하여 약 20% 정도의 높은 항산화력을 갖고 있었다. 또한, HPLC 분석을 통해 해당근 생물 100 g을 기준으로 240 mg의 EGCG와 50 mg의 kaempferol을 함유하는 것으로 나타났다. AGEs에 의해 유도된 HUVEC의 ROS 생성 저해 효과는 해당근 추출물 100, $500\;{\mu}g/mL$ 처리 시 각각 63, 77%로 나타났다. 또한, monocyte adherent assay에서 해당근 추출물은 $100\;{\mu}g/mL$ 처리시 정상을 0%로 하였을 때 AGEs에 의해 유도된 단핵구 부착을 33%, $500\;{\mu}g/mL$ 처리시 약 75% 정도로 농도 의존적으로 부착을 저해하는 것을 관찰할 수 있었으며, 유도되지 않은 HUVEC의 저항은 $113{\Omega}{\cdot}cm^2$ 에서 glycer-AGEs 처리 시 $88{\Omega}{\cdot}cm^2$로 낮아진 것을 해당근 추출물을 $100\;{\mu}g/mL$ 처리 시 약 $102{\Omega}{\cdot}cm^2$, $500\;{\mu}g/mL$ 처리시 약 $106{\Omega}{\cdot}cm^2$로 저항의 감소를 억제하는 것을 관찰할 수 있었다.

• Journal of Ginseng Research
• /
• 제45권2호
• /
• pp.344-353
• /
• 2021

Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were grown in normal or KRGE-supplemented medium. Furthermore, they were transfected with heme oxygenase-1 (HO-1) gene or treated with its inhibitor, a NF-κB inhibitor, and a miR-155-5p mimic or inhibitor. Senescence-associated characteristics of endothelial cells were determined by biochemical and immunohistochemical analyses. Results: Treatment of HUVECs with KRGE resulted in delayed onset and progression of senescence-associated characteristics, such as increased lysosomal acidic β-galactosidase and decreased telomerase activity, angiogenic dysfunction, and abnormal cell morphology. KRGE preserved the levels of anti-senescent factors, such as eNOS-derived NO, MnSOD, and cyclins D and A: however, it decreased the levels of senescence-promoting factors, such as ROS, activated NF-κB, endothelial cell inflammation, and p21 expression. The beneficial effects of KRGE were due to the induction of HO-1 and the inhibition of NF-κB-dependent biogenesis of miR-155-5p that led to the downregulation of eNOS. Moreover, treatment with inhibitors of HO-1, NF-κB, and miR-155-5p abolished the anti-senescence effects of KRGE. Conclusion: KRGE delayed or prevented HUVEC senescence through a signaling cascade involving the induction of HO-1, the inhibition of NF-κB-dependent miR-155-5p biogenesis, and the maintenance of the eNOS/NO axis activity, suggesting that it may protect against vascular diseases associated with endothelial senescence.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권1호
• /
• pp.1-13
• /
• 2016

The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions.

• Clinical and Experimental Pediatrics
• /
• 제45권3호
• /
• pp.295-301
• /
• 2002

미세혈관의 모든 분절(세동맥, 모세혈관, 세정맥)에 있는 내피세포의 기능은 허혈-재관류(ischemia-reperfusion)에 노출시 장애가 발생하게 되는데, 세동맥에서는 혈관확장 능력이 떨어지고, 모세혈관에서는 체액 여과 및 백혈구에 의한 혈관의 막힘(leukocyte plugging)이 증가되며, 세정맥에서는 백혈구-내피세포 접착(leukocyte-endothelial cell adhesion)과 단백의 혈관 외 누출이 증가한다. 활성 산소(reactive oxygen species)와 nitric oxide의 생산의 불균형은 이들 반응을 촉진시키며, 심혈관 질환의 위험 인자인 hypercholesterolemia, 당뇨병, 고혈압 등은 I/R에 대한 미세혈관 반응을 더욱 악화시킨다.

• 고려인삼학회:학술대회논문집
• /
• 고려인삼학회 2008년도 춘계 학술대회
• /
• pp.85-85
• /
• 2008

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권3호
• /
• pp.185-195
• /
• 2000

Vascular diseases are significant complications of diabetes mellitus (DM), and the endothelial cells may play a pivotal role in the development of vascular disease in DM. Endothelin-1 (ET-1) released from endothelium is a potent vasoconstrictor peptide and circulating level of ET-1 is increased in a variety of disease states. The purpose of this study was to determine the changes of responsiveness to ET-1 in DM, and we experimented on the changes in the ET-1-induced contraction, levels of nitrite and lipid peroxidation, and ET-1 immunoreactivity in aorta from streptozotocin-induced DM rats. DM was induced by single injection of streptozotocin (55 mg/kg, i.p.). The immunoreactive ET-1 levels in endothelial layer of thoracic aorta were much higher in DM rats than control rats. Nitrite in tissue homogenate was decreased and plasma nitrite was increased in DM rats. Malondialdehyde (MDA) was significantly increased in DM rats and cGMP was not significantly different between control and DM rats. ET-1 produced concentration- dependent contractile responses that are significantly attenuated in DM rats compared to controls. In the presence of selective $ET_A$ receptor antagonist BQ610, the maximum contraction was decreased and the concentration ratios for BQ610 yielded $pA_2$ values of 7.3 (slope, 0.65) in control rats, whereas BQ610 had no antagonistic effect on ET-1-induced contraction in DM rats. However, pretreatment with BQ788, an $ET_B$ receptor antagonist, maximum response was decreased and the dose-response curves for ET-1 were shifted to the right in both groups and $pA_2$ values were 7.9 and 7.7 (slope, 1.05 in control and DM rats), respectively. IRL 1620 and sarafotoxin S6c, $ET_B$ agonists, induced relaxation in control rats but not in DM rats. These results indicate that endothelial cell dysfunction and enhanced immunoreactivity of ET-1 have been found in DM rat and ET-1-induced contraction was attenuated in DM rat. These attenuated responses might be at least in part caused by the alteration of $ET_A$ receptor properties (e.g. desensitization), and partly related with an alteration in intracellular mechanism for contraction to ET-1.

• 동의생리병리학회지
• /
• 제20권6호
• /
• pp.1658-1663
• /
• 2006

Panax notoginseng (Buck) F.H chen. root (PNS) is used as a therapeutic agent to stop haemorrhages and a tonic to promote health in Korean and Chinses medicine. The pharmacokinetic profiles of the main PNS are still not accurately investigated. Our preliminary aim is to elucidate the pharmacokinetics features of the PNS in rats. Objective of this study is to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). No has been found to be a modulator of the adhesive interactions between platelet and endothelial cells. Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg pre day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-${\alpha}$ and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an No synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-${\alpha}$ levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-${\alpha}$ production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect like corticosteroid effect.

• Journal of Ginseng Research
• /
• 제32권3호
• /
• pp.244-249
• /
• 2008

Vascular inflammation is an important step in the development of cardiovascular disorder. Since it has not been known whether Korean red ginseng has a role to play on the vascular inflammation, we investigated the effects of Korean red ginseng extract (KRGE) on monocyte adhesion and its underlying signaling mechanism. Monocyte adhesion assay and Western blot were conducted on the human umbilical vein endothelial cells to study monocyte adhesion and the expression of adhesion molecules. Intracellular calcium was measured with Fura-2 fluorescent staining, and superoxide production was measured with lucigenin chemiluminescence in the endothelial cells. KRGE inhibits tumor necrosis factor (TNF)-alpha-induced monocyte adhesion on the endothelial cells at the range of $0.03{\sim}1$ mg/ml. TNF-alpha-induced vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 expression were inhibited by the pretreatment of KRGE in the endothelial cells. KRGE also inhibits TNF-alpha-induced intracellular calcium and the superoxide production in the endothelial cells. This study first demonstrated that KRGE inhibits TNF-alpha-induced monocyte adhesion by inhibiting the adhesion molecule expression, intracellular calcium and superoxide production in the endothelial cells. Therefore, the anti-inflammatory function of KRGE may be contributed to protecting the endothelial dysfunction in the vascular inflammatory disorders.

• Journal of Korean Neurosurgical Society
• /
• 제59권6호
• /
• pp.544-550
• /
• 2016

Objective : Cerebral endothelial cells have unique biological features and are fascinating candidate cells for stroke therapy. Methods : In order to understand the molecular mechanisms of human cerebral endothelial cell (hCMEC/D3) transplantation in a rat stroke model, we performed proteomic analysis using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein expression was confirmed by quantitative real-time PCR and Western blot. Results : Several protein spots were identified by gel electrophoresis in the sham, cerebral ischemia (CI), and CI with hCMEC/D3 treatment cerebral ischemia with cell transplantation (CT) groups, and we identified 14 differentially expressed proteins in the CT group. Proteins involved in mitochondrial dysfunction (paraplegin matrix AAA peptidase subunit, SPG7), neuroinflammation (peroxiredoxin 6, PRDX6), and neuronal death (zinc finger protein 90, ZFP90) were markedly reduced in the CT group compared with the CI group. The expression of chloride intracellular channel 4 proteins involved in post-ischemic vasculogenesis was significantly decreased in the CI group but comparable to sham in the CT group. Conclusion : These results contribute to our understanding of the early phase processes that follow cerebral endothelial cell treatment in CI. Moreover, some of the identified proteins may present promising new targets for stroke therapy.

• Journal of Ginseng Research
• /
• 제21권2호
• /
• pp.119-124
• /
• 1997

Chronic hypertension is associated with impaired endothelial function such as reduced synthesis/release of endothelium-derived relaxing factor(EDRF, nitric oxide) and increased synthesis/release of endothelium-derived contracting factor(EDCF) including prostaglandin endoperoxide($PGH_2$) , superoxide anion both in animals and in humans. We have previously shown that ginsenosides lower the blood pressure and enhance the release of nitric oxide(NO) from endothelial cells in the rat aorta of the normotensive rats. The aim of the present study is to examine whether in vivo treatment of spontaneously hypertensive rats(SHRs) with protopanaxatriol ginsenosides(PPT) reduces the blood pressure and improves endothelial function in the isolated thoracic aorta of SHR. In addition, the contractile response to $PGH_2$ and superoxide anion in the aorta treated with PPT was assessed. SHRs at the age of 16 weeks were savaged with PPT(30 mg/kg/ day) for 2 weeks and systolic blood pressure was measured by the tail-cuff method. Whereas blood pressure was significantly increased in SHRs by 5.4 mmHg during this period of treatment, treatment of SHRs with PPT blocked the elevation of blood pressure. Endothelium-dependent relaxation to acetylcholine was significantly increased in the PPT-treated animals. $PGH_2$- and oxygen-derived free radical-induced contractions were significantly suppressed in aortic rings without endothelium from PPT-treated SHR. These findings indicate that PPT reduces the blood pressure of SHR, which may be associated with either increase of NO release or by antagonizing superoxide anion and PGH2 in the aortic smooth muscle.