• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.544-559
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• 2007

Objectives : This study was designed to evaluate the anti-diabetes and vasoelasticity effects of Mori Folium and Aurantii Fructus in streptozotocin-induced type II diabetes mellitus model. Methods : The anti-diabetic effect of Mori Folium and Aurantii Fructus on rats induced with diabetes by streptozotocin was investigated through analyses of changes in body weight, blood glucose, urine volume of rats, viability of human umbilical vein endothelial cells(HUVECs), and elasticity of descending thoracic aorta in rats. The subjects in this study were divided into four groups(n=15): a normal group without any treatment (Con), a normal group with Mori Folium and Aurantii Fructus treatment(Con+P), a diabetes group induced by streptozotocin(STZ), and a Mori Folium and Aurantii Fructus treatment group under diabetes induced by streptozotocin(STZ+P). Rats were administered streptozotocin to induce diabetes. Results : The study showed that Mori Folium and Aurantii Fructus significantly reduced highly increased blood glucose levels(p<0.01) and prevented the diabetic rats from weight loss(p<0.01) and polyurea(p<0.05), Mori Folium and Aurantii Fructus also recovered decreased viability of HUVECs(p<0.01) and damaged elasticity of aorta induced by the streptozotocin (p<0.01). Conclusions: It was concluded from the results that Mori Folium and Aurantii Fructus have a distinct anti-diabetes effect and they also prevent damage of blood vessel induced by diabetes. resulting in prevention of cardiovascular diseases ascribed to diabetes.

• The Korean Journal of Food And Nutrition
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• v.31 no.3
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• pp.328-334
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• 2018

The purpose of this study was to examine the effects of Maca water and/or ethanol extract on the nitric oxide (NO) production in human umbilical vein endothelial cells HUVAC and on erectile dysfunction in rats. Maca was extracted due to both solutions, which are water and ethanol. Each Maca extract was applied to HUVAC, and NO production was checked. Additionally, three different dosages (250, 500 and 1,000 mg/kg) of Maca ethanol extract was administered to Sprague-Dawley rats for 4 weeks. All rats were sacrificed and each sample was collected for analysis. The control rats received only the saline vehicle. The NO production of HUVAC was significantly increased by domestic and homemade Maca water extracted at $60^{\circ}C$ group. Both NO generation and testosterone release were not influenced due to the oral administration of Maca. In the EtOH group rats, the number of sperm was reduced compared to that of the control group. All Maca groups had a high number of sperm and each sperm count had increased as a result of the Maca extract dose. The results of this research suggest that Maca has a positive effect on male erectile dysfunction, which need to be examined further in future studies.

• The Journal of Internal Korean Medicine
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• v.37 no.4
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• pp.591-600
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• 2016

Objective: This study aimed to examine the relaxation effects and underlying mechanisms of Cynomorii herba (CH) extract in isolated rabbit corpus cavernous tissues.Methods: We experimented with CH extract (0.01-3.0 mg/mL). Nω-nitro-L-arginine (L-NNA) was experimented before the CH extract to contracted strips induced by phenylephrine (PE, 1 μM)and compared with nonexperimented. In addition, we experimented with calcium chloride (Ca²⁺, 1 mM) after pretreatment of the CH extract in Ca²⁺-free Krebs-Ringer solution to contracted strips induced by PE. The cell viability and nitric oxide (NO) concentration of human umbilical vein endothelial cells (HUVECs) were measured by an methylthiazol-2-yl-2, 5-diphenyl tetrazoliumbromide (MTT) assay and Griess reagent system. The ratio of smooth muscles to collagen fibers, in addition to eNOS- and PDE-5-positive reactions, was examined by histochemical and immunohistochemical staining.Results: The CH extract significantly induced the relaxation of the cavernous strips, and the pretreatment with L-NNA inhibited CH extract-induced relaxation. The L-NNA pretreatment reduced the increased contraction induced by the addition of Ca²⁺in Ca²⁺-free solution. Furthermore, the NO concentration of the HUVECs increased. When the CH extract was applied to the corpus cavernosum of the penis (CCP) of Sprague Dawley rats, the ratio of smooth muscles to collagen fibers by PE and the formation of eNOS around the helicine artery increased. However, the CH extract treatment decreased PDE-5 positive reactions.Conclusions: These results show that the relaxation effects induced by the CH extract are associated with the suppression of the influx of extracellular Ca²⁺ via the production of NO and eNOS and inhibition of PDE-5.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.467-473
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• 2024

In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.

• Journal of Nutrition and Health
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• v.36 no.9
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• pp.908-917
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• 2003

It has been proposed that oxidative modification of LDL (oxLDL) plays a significant role in the pathogenicity of atherogenesis. We tested the hypothesis that chitin and chitosan may function as antioxidants with respect to 0.1 mg cholesterol/ml LDL incubated with 5 $\mu$ M Cu$^2$$^{+}$alone or in the P338Dl mouse macrophage system using L-ascorbic acid as a standard classical antioxidant. The degree of oxLDL formation was ascertained by the relative electrophoretic mobility (rEM) in the combination of thiobarbituric acid reactive substances (TBARS) levels, and the cytotoxicity of oxLDL was detected by macrophage viability. The oxLDL uptake and foam cell formation of macrophages were measured by Oil Red O staining. Incubation with Cu$^2$$^{+}$and macrophages increased rEM of LDL and stimulated TBARS formation. Culture of macrophages with LDL in the presence 5 $\mu$ M Cu$^2$$^{+}$induced macrophage death. In cell-free system 200 $\mu$g/ml water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation. Water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation near-completely relative to L-ascorbic acid, whereas water-soluble chitin and chitin-oligosaccharide had no measurable antioxidant effect. In macrophage system water-soluble chitosan and chitosan-oligosaccharide blocked oxidation of LDL with a significant increase in cell viability, and decreased TBARS in medium. As for the inhibitory effect on macrophage foam cell formation, chitosan and its oligosaccharide, but not watersoluble chitin, revealed the effectiveness. The endothelial expression of lectin-like oxLDL receptor-1 (LOX-1) was tested by Western blot analysis, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide blocked LOX-1 expression. These results indicate that water-soluble chitosan and its oligosaccharide showed the inhibitory effect on Cu$^2$$^{+}$-induced LDL oxidation of macrophages, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide had blocking effect on oxLDL receptor expression in the human umbilical vein endothelial system. Thus, water-soluble chitosan and its oligosaccharides possess anti-atherogenic potentials possibly through the inhibition of macrophage LDL oxidation or endothelial oxLDL receptor expression depending on chemical types.l types.

• Journal of Life Science
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• v.33 no.9
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• pp.703-712
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• 2023

Angiogenesis, the formation of blood vessels from pre-existing vessels, is a multistep process regulated by modulators of angiogenesis. It is essential for various physiological processes, such as embryonic development, chronic inflammation, and wound repair. Dysregulation of angiogenesis causes many diseases, such as cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. However, the number of effective anti-angiogenic drugs is limited. Recent research has focused on identifying potential drug candidates from natural sources. For example, marine natural products have been shown to have anti-cancer, anti-oxidant, anti-inflammatory, antiviral, and wound-healing effects. Thus, this study aimed to describe the angiogenesis inhibitory effect of Hizikia fusiforms (brown algae) extract. The hexane extract of H. fusiformis has shown inhibitory effects on in vitro angiogenesis assays, such as cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVECs). The hexane extract of H. fusiformis (HFH) inhibited in vivo angiogenesis in a mouse Matrigel gel plug assay. In addition, the protein expression of vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal kinase, and AKT serine/threonine kinase 1 decreased following treatment with H. fusiformis extracts. Our results demonstrated that the hexane extract of H. fusiformis (HFH) inhibits angiogenesis in vitro and in vivo.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4369-4376
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• 2015

Background: To investigate in-vitro antagonistic effect of low-dose liquiritigenin on gemcitabine-induced capillary leak syndrome (CLS) in pancreatic adenocarcinoma via inhibiting reactive oxygen species (ROS)-mediated signalling pathways. Materials and Methods: Human pancreatic adenocarcinoma Panc-1 cells and human umbilical vein endothelial cells (HUVECs) were pre-treated using low-dose liquiritigenin for 24 h, then added into gemcitabine and incubated for 48 h. Cell viability, apoptosis rate and ROS levels of Panc-1 cells and HUVECs were respectively detected through methylthiazolyldiphenyl-tetrazoliumbromide (MTT) and flow cytometry. For HUVECs, transendothelial electrical resistance (TEER) and transcellular and paracellular leak were measured using transwell assays, then poly (ADP-ribose) polymerase 1 (PARP-1) and metal matrix proteinase-9 (MMP9) activity were assayed via kits, mRNA expressions of p53 and Rac-1 were determined through quantitative polymerase chain reaction (qPCR); The expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and PARP-1 were measured via western blotting. Results: Low-dose liquiritigenin exerted no effect on gemcitabine-induced changes of cell viability, apoptosis rate and ROS levels in Panc-1 cells, but for HUVECs, liquiritigenin ($3{\mu}M$) could remarkably elevate gemcitabine-induced decrease of cell viability, transepithelial electrical resistance (TEER), pro-MMP9 level and expression of ICAM-1 and VCAM-1 (p<0.01). Meanwhile, it could also significantly decrease gemcitabine-induced increase of transcellular and paracellular leak, ROS level, PARP-1 activity, Act-MMP9 level, mRNA expressions of p53 and Rac-1, expression of PARP-1 and apoptosis rate (p<0.01). Conclusions: Low-dose liquiritigenin exerts an antagonistic effect on gemcitabine-induced leak across HUVECs via inhibiting ROS-mediated signalling pathways, but without affecting gemcitabine-induced Panc-1 cell apoptosis. Therefore, low-dose liquiritigenin might be beneficial to prevent the occurrence of gemcitabine-induced CLS in pancreatic adenocarcinoma.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.41-49
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• 2008

Background : The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo. Materials and methods : To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons. Results : The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons. Conclusion : Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.59-67
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• 2018

Objectives : Ojeoksan, originally recorded in an ancient Korean medicinal book named "Donguibogam" and has been used for the treatment of circulation disorder of blood which was called blood accumulation (血積) in Korean medicine. Therefore, this study was carried out to investigate the beneficial effect of OJS on vascular inflammation in HUVECs. Methods : We evaluated the effect of OJS on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-${\alpha}$ by using Western blot. Results : Pretreatment with OJS decreased the adhesion of HL-60 cells to TNF-${\alpha}$-induced HUVEC. OJS suppressed TNF-${\alpha}$-induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and endothelial cell selectin (E-selectin). Moreover, OJS significantly decreased TNF-${\alpha}$-induced production of intracellular reactive oxygen species (ROS); and inhibited the phosphorylation of $I{\kappa}B-{\alpha}$ in the cytoplasm compared to the experimental group. Pretreatment with OJS inhibited the trans-location of NF-${\kappa}B$ p65 to the nucleus. OJS also inhibited phosphorylation of MAPKs compared to the experimental group. OJS significantly increased the protein expression of Nrf2 and HO-1. Conclusions : Ojeoksan has a protective effect on vascular inflammation, and might be a potential therapeutic agent for early atherosclerosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1134-1141
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• 2002

Adhesion of leukocytes to the activated vascular endothelium and their subsequent recruitment/migration into the artery wall are key features in the pathogenesis of atherosclerosis and inflammatory diseases. These features have been mediated by cell adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) and in tracellular cell adhesion molecule-1 (ICAM-1). This study examined whether flavonoids inhibit the pro-inflammatory cytokine TNF-$\alpha$-induced monocyte adhesion via a modulation of the protein expression of VCAM-1 and ICAM-1 of human umbilical vein endothelial cells (HUVECs). TNF-$\alpha$ markedly increased the adhesion of THP-1 monocytes to endothelial cells and induced the expression of VCAM-1, ICAM-1 and E-selectin proteins in HUVECs. Micromolar concentrations of the flavones luteolin and apigenin and the flavonol quercetin near completely blocked the monocyte adhesion to the activated endothelial cells and the induction of these adhesion molecules. However, equimicromolar catechins of (-)epigallocatechin gallate and (+)catechin, the flavonol myr- icetin and the flavanones of naringin and hesperidin had no effect on TNF-$\alpha$-activated monocyte adhesion. (-)Epigallocatechin gallate, (+) catechin, and naringin did not attenuate the TNF-$\alpha$ induction of these adhesion molecules. Furthermore, culture with luteolin and apigenin strongly blocked the expression of TNF-$\alpha$-induced VCAM-1 mRNA and modestly attenuated ICAM-1 mRNA. Quercetin modestly decreased the TNF-$\alpha$-activated VCAM-1 and ICAM-1 mRNAs. These results demonstrate that flavonoids classified as flavones and flavonols may inhibit monocyte adhesion to the TNF-$\alpha$-activated endothelium, most likely due to a blockade of expression of functional adhesion molecules down-regulated at the transcriptional level, indicating a definite linkage between the chemical structure of flavonoids and the expression of cell adhesion molecules. Furthermore, the antiathero-genic feature of flavonoids appears to be independent of their antioxidant activity.