• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.123-129
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• 2009

Aprotinin is used clinically in cardiopulmonary bypass surgery to reduce transfusion requirements and the inflammatory response. The mechanism of action for the anti-inflammatory effects of aprotinin is still unclear. We examined our hypothesis whether inhibitory effects of aprotinin on cytokine-induced inducible nitric oxide synthase (iNOS) expression (IL-$l\beta$ plus TNF-$\alpha$), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-l induction in rat VSMCs. Aprotinin induced HO-l protein expression in a dose-dependent manner, which was potentiated during inflammatory condition. Aprotinin reduced cytokine mixture (CM)-induced iNOS expression in a dose dependent manner. Furthermore, aprotinin reduced CM-induced ROS generation, cell proliferation, and phosphorylation of JNK but not of P38 and ERK1/2 kinases. Aprotinin effects were reversed by pre-treatment with the HO-l inhibitor, tin protoporphyrin IX (SnPPIX). HO-l is therefore closely involved in inflammatory-stimulated VSMC proliferation through the regulation of ROS generation and JNK phosphorylation. Our results suggest a new molecular basis for aprotinin anti-inflammatory properties.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1132-1138
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• 2009

Vascular inflammation is an important event in the development of vascular diseases such as tumor progression and atherosclerosis. This study was to investigate the inhibitory effects of WK-38, a new herbal prescription for the treatment of atherosclerosis, on vascular inflammation in human umbilical vein endothelial cells (HUVEC). WK-38 is composed of Rhei Rhizoma, Magonoliae Cortex, Moutan Cortez Radicis. Pretreatment with WK-38 was significantly blocked TNF-$\alpha$-induced expression level of cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and endothelial cell selectin (E-selectin) in a dose-dependent manner. TNF-$\alpha$-induced cell adhesion in co-cultured U937 and HUVEC was also blocked by pretreatment with WK-38. Moreover, WK-38 significantly suppressed p65 NF-${\kappa}B$ translocation into the nucleus by TNF-$\alpha$ as well as the phosphorylation and degradation of $I{\kappa}B-{\alpha}$. In conclusion, the present data suggested that WK-38 could suppress TNF-$\alpha$-induced vascular inflammatory process, though inhibition of NF-${\kappa}B$ activation in HUVEC.

• Clinical and Experimental Pediatrics
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• v.57 no.11
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• pp.472-478
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• 2014

Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term.

• Fisheries and Aquatic Sciences
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• v.25 no.2
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• pp.90-100
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• 2022

Cardiovascular diseases (CVDs) have posed serious public health problems, accounting for nearly 30% of mortality worldwide and their incidence is still increasing. Therefore, new treatment resources are necessary to prevent or manage the ever-increasing population of patients with CVDs. Sea cucumber is well known for its medical and health benefit effects, but it is not well known what/how effect it has on vascular disease. In the present study, we examined the protect effect of sea cucumber, Apostichopus japonicus 80% ethanol extract (AJE) on zebrafish embryo with the stimulation of free fatty acid, palmitate (PA). In vivo study showed that AJE can attenuate PA-induced toxicity through relieving the rapid heartbeat, increasing the survival rate and reducing the malformation in both wild type and Tg (fli1a:eGFP) transgenic zebrafish lines. Additionally, compare with PA treated embryos, the yolk sac area, body length, axial vascular segment (AVS) and intersegmental vessel (ISV) of the co-treatment group of AJE and PA were comparable to the control group. Moreover, AJE lowered the expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and inflammation-related genes induced by PA, and inhibited PA-induced vascular development disorders. Our data preliminarily verify that AJE could be a candidate resource for the prevention or therapy of CVDs.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.3
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• pp.20-31
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• 2019

Objectives: The seeds from Arctium lappa have been considered for its various pharmacological properties, which include anti-carcinogenic, anti-inflammatory, anti-diabetic, and anti-viral activities. Methods: In the present study, we investigated the anti-inflammatory effect of the ethanol extract from the seeds of Arctium lappa L (EAL) on cytokine-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC). Results: Pretreatment with EAL significantly decreased tumor necrosis factor alpha ($TNF-{\alpha}$)-induced cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) in a dose-dependent manner. Cell adhesion assay showed that pretreatment with EAL suppressed HUVEC-monocyte adhesion by $TNF-{\alpha}$ over $1{\mu}g/ml$ concentration. We investigated the involvement of nuclear transcription factor kappa-B ($NF-{\kappa}B$) in $TNF-{\alpha}$-induced vascular inflammation. $NF-{\kappa}B$ p65 nuclear expression was induced by $TNF-{\alpha}$, however, pretreatment with EAL was attenuated that nuclear translocation. In cytoplasm, EAL was also attenuated $TNF-{\alpha}$-induced decrease of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) expression. Moreover, EAL significantly decreased $TNF-{\alpha}$-induced production of intracellular reactive oxygen species (ROS). Conclusions: Taken together, our findings suggest that seeds of Arctium lappa L could be a therapeutic herb for prevention of cardiovascular diseases throughout the inhibition of vascular endothelial inflammation.

• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1061-1066
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• 2003

The fruit of Actinidia polygama (AP) has long been used as a folk medicine in Korea for treating pain, rheumatic arthritis and inflammation. The present investigation was carried out to determine the in vivo and in vitro anti-inflammatory activity of AP using several animal models of inflammation. The 70% ethanol extract of the fruit of AP significantly inhibited acetic acidinduced, vascular permeability in a dose dependent manner (23%, 38%, and 41 % inhibition at doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg, respectively). This effect was maintained in AP water-soluble fraction (APW). The APW fraction also showed significant inhibitory activity against the rat paw edema induced by a single treatment of carrageenan. In vitro experiments were performed to demonstrate the inhibitory activities of APW (100 $\mu$ g/ml) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production. The results showed that APW dose-dependently suppressed LPS-induced NO production in RAW 264.7 macrophages without a notable cytotoxic effect and also decreased inducible NO synthase (iNOS) protein expression. APW also showed a significant inhibitory effect in LPS-induced $PGE_2$ production and cyclooxygenase-2 (COX-2) expression.

• IMMUNE NETWORK
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• v.24 no.1
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• pp.10.1-10.17
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• 2024

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

• BMB Reports
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• v.48 no.9
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• pp.519-524
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• 2015

Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether three structurally related polyphenols found in the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS) and activation of nuclear factor (NF)-κB. Remarkably, all of the above mentioned vascular inflammatory effects of HG were attenuated by pretreatment with baicalin, baicalein, and wogonin. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications, therefore, our results suggest that baicalin, baicalein, and wogonin may have significant therapeutic benefits against diabetic complications and atherosclerosis. [BMB Reports 2015; 48(9): 519-524]

• Herbal Formula Science
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• v.20 no.1
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• pp.1-11
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• 2012

Objectives : This experimental study was designed to investigate the inhibitory effects of combination with Korean red ginseng and Gastrodia rhizoma on vascular dysfunction in high-fat/cholesterol diet-induced hyperlipidemia. Methods : Sprague-Dawley rats were fed with 7.5% cocoa butter and 1.25% cholesterol for 10 weeks, with Panax ginseng (PG), and mixtures of Panax ginseng and Gastrodia rhizoma (PGM), respectively. Results : Chronic treatment with PG and PGM significantly decreased body weight. The aortic expression of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were markedly increased in hyperlipidemia rats. Interestingly, PGM significantly decreased cell adhesion molecules expression. However, there was no significant decrease in PG group. In addition, PG and PGM group inhibited high-fat/cholesterol diet-induced cytokine such as monocyte chemoattractant protein (MCP-1) mRNA expression. Furthermore, PG and PGM group significantly decreased c-reactive protein protein (CRP) level. Especially, PGM significantly accentuated the decrease of MCP-1 mRNA expression and CRP level. Conclusions : the present study provides an evidence that combination with Panax ginseng and Gastrodia rhizoma enhances anti-vascular protective effects through suppression of vascular inflammation in hyperlipidemic rats.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.51 no.2
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• pp.127-134
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• 2018

Arteriosclerosis is the major cause of coronary artery and cerebrovascular disease, which are leading causes of death. Pro-inflammatory cytokines induce injury to vascular endothelial cells by increasing cell adhesion molecules, leading to vascular inflammation, a major risk factor for the development of arteriosclerosis. In the current study, we investigated the inhibitory effect of enzymatic hydrolysate from Japanese mud shrimp Upogebia major on the inflammation of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$)-stimulated human umbilical vein endothelial cells (HUVECs). We first evaluated the antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities of eight U. major enzymatic hydrolysates: alcalase, papain, ${\alpha}$-chymotrypsin (${\alpha}-Chy$), trypsin, pepsin, neutrase, protamex and flavourzyme. Of these, ${\alpha}-Chy$ exhibited potent antioxidant and ACE inhibitory activities. The ${\alpha}-Chy$ hydrolysate was fractionated by two ultrafiltration membranes of 3 and 10 kDa. The ${\alpha}-Chy$ hydrolysate of U. major and its molecular weight cut-off fractions resulted in a significant reduction in NO production and a decrease in cell adhesion molecules [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial-selectin (E-selectin)] and pro-inflammatory cytokines [interleukin-6 (IL-6), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1)] in $TNF-{\alpha}$-stimulated HUVECs. These results suggest that enzymatic hydrolysate from U. major can be used in the control and prevention of vascular inflammation and arteriosclerosis.