• The Korea Journal of Herbology
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• v.24 no.4
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• pp.77-86
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• 2009

Objectives : The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Nelumbo nucifera leaves (NNL) on the proliferation and migration of HASMC. Additionally, the mechanisms involved in any observed effects were also evaluated. Methods : Apoptotic cells were measured by staining with FITC-labeled annexin V, followed by flow cytometric analysis. The expression level of apoptosis related proteins was confirmed by western blot. And MMP-9 activity was measured by gelatin zymography and MMP-9 expression was measured by ELISA Results : NNL completely inhibited the proliferation of HASMC via induction of the expression of apoptotic proteins including annexin V, cleaved poly ADP-ribose polymerase (PARP), and caspase-3 and -8. NNL treatment resulted in the release of cytochrome c into cytosol, a loss of mitochondrial membrane potential, a decrease in Bcl-2 and Bcl-xL and an increase in Bax expression. NNL also blocked HASMC migration via suppression of MMP-9. Conclusions : Taken together, these results indicate that NNL has the potential for use as an anti-artherosclerosis agent.

• The Korea Journal of Herbology
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• v.24 no.4
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• pp.55-62
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• 2009

Objectives : This study was designed to investigate the effects of an aqueous extract from Buddleja officinalis Maxim (ABO) on vascular dysfunction in low-density lipoprotein receptor deficient (LDLr KO) mice. Methods : Present study showed that LDLr KO mice were fed a high fat diet consisting of 60 kcal% fat, with or without 200 mg/day/kg ABO of diet, for 14 weeks. Results : High fat diet-LDLr KO mice were treated with ABO were completely normalized by lowering glucose. ABO reduced intima/media thickness in a high fat diet-LDLr KO mice without affecting plasma cholesterol and triglyceride levels. ABO caused endothelium-dependent relaxation in the acetylcholine-precontracted aorta of high fat diet-LDLr KO mice. ABO increased eNOS expression, while decreased cell adhesion molecules expression in high fat diet-LDLr KO mice. Conclusions : In conclusion, chronic treatment with ABO improved hyperglycemia and endothelium-dependent vascular relaxation as well as exhibited anti-inflammatory effect in diabetic atherosclerotic mouse model, independent of effects on plasma lipids.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1055-1060
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• 2004

Apoptosis is the ability of cells to self-destruct by the activation of an intrinsic cellular suicide program when the cells are no longer needed or when they are seriously damaged. Morphologically, apoptosis is characterized by the appearance of membrane blebbing, cell shrinkage, chromatin condensation, DNA cleavage, and the fragmentation of the cell membrane-bound apoptotic bodies. Siegesbeckia glabrescens Makino (Siegesbeckiae Herba, SG) has been widely used as treatments for arthritis, and fever, as well as detoxification properties. The present studies were undertaken to evaluate if SG has an anti-apoptotic property. Cell viability was measured by XTT and tryphan blue stain. Morphological characteristic of human aortic smooth muscle cells(HASMC) were visualized with a phase-contrast microscope. SG significantly reduced HASMC, but not human umbilical vein endothelial cell(HUVEC), viability in a dose-dependent manner. Confluent untreated cells at 24hrs showed normal morphology, flat with a uniform polygonal shape. SG-treated cells (0.5㎎/㎖) at 24hrs showed apoptotic morphology. Cells became irregular with elongated lamellipodia, and exhibited condensed chromatin in nuclei with occasional endoucleation. There was an increase in the number of apoptotic cells rounding-up and being detached from the substrate. TUNEL staining of SG-treated cells showed dark-brown stains in nuclei and cytosol. Caspases are central components of the machinery responsible for apoptosis and are generally divided into two categories; the initiator caspases, which include caspases-2,-8,-9, and -10, and the effector caspases, which include caspases-3,-6, and -7. SG decreased anti-caspase-3 protein expression, which means activation of caspases-3 activity. It has been reported that there is a link between NO formation and apoptosis. NO production was accelerated by SG treatment in HASMC. L-NNA, NOS inhibitor, inhibited SG-induced apoptosis. These results, therefore, indicated that both caspases-3 and NO production are involved in apoptosis in smooth muscle cells. According to these results, SG may have a potential effect in the treatment of hypertensive atherosclerosis.

• Herbal Formula Science
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• v.25 no.4
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• Journal of Life Science
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• v.19 no.7
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• pp.976-982
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• 2009

Little is known about the cardiovascular roles of alliin, a functional component in garlic that has been used as food material. Thus, we examined a broad range of cardiovascular activities of alliin in this study. From our in vitro experiments, alliin was determined to act as a stimulant to induce endothelial cell proliferation and endothelial cell migration. Since endothelial cell proliferation and migration are highly associated with angiogenesis and wound healing, alliin is suggested as a regulator to control angiogenesis and wound healing. In addition, alliin was elucidated to prevent lipopolysaccharide (LPS)-induced adhesion of THP-1 leukocytes to endothelial cells and LPS-induced homotypic THP-1 cell aggregation. These inhibitory effects indicate that alliin is likely to act as an anti-atherosclerotic and anti-thrombotic factor, because leukocytic adhesion to endothelial cells and homotypic leukocyte aggregation are highly associated with atherosclerosis and thrombosis, respectively. Our additional findings show that alliin has no effect on the production of nitric oxide (NO), an important vasoregulator. In conclusion, alliin is suggested as a regulator for controlling various cardiovascular functions.

• Food Science and Preservation
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• v.23 no.3
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• pp.378-386
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• 2016

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

• Journal of Applied Biological Chemistry
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• v.57 no.1
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• pp.7-15
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• 2014

This study investigated anti-obesity and antioxidant effects of dietary non-fermented soybean crud residue (SCR) and fermented SCR by Monascus pilosus (FSCR) in high-fat induced-obese mice. SCR and FSCR were supplemented with high-fat diet at 2% (wt/wt) dose for 8 weeks. Both SCR and FSCR significantly lowered body weight, epididymal fat weight and weight gain rate compared to high-fat diet control (HC) group and FSCR group showed lowest weight gain rate. In addition, it was observed that serum and hepatic lipid profiles including triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol were significantly improved by supplementing SCR or FSCR. Furthermore, SCR and FSCR administration showed increase of glutathione content and decrease of hepatic lipid peroxide content, serum aminotransferase activity, and hepatic xanthine oxidase activity. On the other hand, activities of reactive oxygen species scavenging enzyme such as superoxide dismutase, glutathione S-transferase and glutathione peroxidase in two test groups were higher than those of HC. Lastly, in comparison with SCR, FSCR was more effective in restoring obesity-related biomarkers to normal level in high-diet induced obese mice. In conclusion, the present study indicates that FSCR could have not only anti-obese effects such as inhibition of abdominal fat accumulation, but also protective effects of cardiovascular disease such as atherosclerosis by decreasing serum and hepatic lipid contents. Furthermore, these results suggest that experimental diets in this study could alleviate hepatic damage caused by overproduction of reactive oxygen spices (ROS) due to obesity via inhibition of ROS generating activities and induction of ROS scavenging activities.

• Journal of Life Science
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• v.30 no.4
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• pp.343-351
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• 2020

Sorbus commixta Hedl. has traditionally been used as a remedy for cough, asthma, and other bronchial disorders. In this study, three major triterpenoids-lupeol, β-sitosterol, and ursolic acid and a coumarin, scopoletin, were isolated from a CHCl₃-soluble fragment of the bark of S. commixta. Their structures were identified by spectroscopic analyses, including mass spectrometry (MS), 1D-, and 2D- nuclear magnetic resonance spectroscopy (NMR), as well as by comparing the data with data reported in the literature. Scopoletin was isolated from this plant for the first time. It is a nutraceutical compound contained in many plants that has been reported to exert diverse biological activities, including anti-inflammatory effects. This study examined the inhibitory effect of scopoletin on TNF-α-induced vascular endothelial inflammation. Unlike the marginal impact of other compounds against low-density lipoprotein (LDL) oxidation and vascular endothelial inflammation, scopoletin showed remarkable activity on LDL oxidation (IC₅₀ = 10.2 μM) and exerted vascular anti-inflammatory effects in EA.hy926 human endothelial cells activated by TNF-α. It suppressed the expression of adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, and blocked the adhesion between THP-1 monocytes and EA. hy926 endothelial cells. It also inhibited TNF-α-induced NF-κB translocation from the cytosol to the nucleus. Moreover, IκBα phosphorylation, which was increased by TNF-α treatment, was reduced after treatment with scopoletin. Thus, scopoletin inhibited TNF-α-induced vascular inflammation in endothelial cells by suppressing the NF-κB signaling pathway. These results demonstrate that owing to its anti-inflammatory activity in the vascular endothelium, scopoletin has the potential to inhibit atherosclerosis development.

• 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.

• Herbal Formula Science
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• v.21 no.2
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• pp.133-143
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• 2013

Objectives : We carry out the simultaneous quantification for quality control of four components in Bangpungtongseong-san (BPTSS) sample. In addition, we assessed the antioxidant effects of BPTSS sample. Methods : The used column for separation and analysis of four compounds was Luna C18 column and column oven temperature was maintained at $40^{\circ}C$. The mobile phase for simultaneous determination consisted of two solvent systems, 1.0% acetic acid in water and 1.0% acetic acid in acetonitrile. High performance liquid chromatography-photodiode array (HPLC-PDA) method for analysis was performed at a flow rate of 1.0 mL/min with PDA detection at 254 and 280 nm. The injection volume was 10 ${\mu}L$. The antioxidant activities of BPTSS were evaluated by measuring free radical scavenging activities on 2,2'-Azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) and 1-1-diphenyl-2-picrylhydrazyl (DPPH). The inhibitory effects on low-density lipoprotein (LDL) oxidation were evaluated by the formation of thiobarbituric acid relative substances (TBARS) and relative electrophoretic mobility (REM). Results : Calibration curves were acquired with $r^2{\geq}0.9999$. The values of limit of detection (LOD) and quantification (LOQ) were 0.06-0.29 ${\mu}g/mL$ and 0.20-0.98 ${\mu}g/mL$, respectively. The amounts of geniposide, liquiritin, baicalin, and glycyrrhizin in BPTSS were 5.06, 7.33, 27.56, and 7.81 mg/g, respectively. The BPTSS showed the radical scavenging activity in a dose-dependent manner. The concentration required for 50% reduction (RC50) against ABTS and DPPH radicals were 72.51 ${\mu}g/mL$ and 128.49 ${\mu}g/mL$. Furthermore, GMGHT reduced the oxidation properties of LDL induced by CuSO4. Conclusions : The established HPLC-PDA method will be helpful to improve quality control of BPTSS. In addition, BPTSS has potentials as therapeutic agent on anti-atherosclerosis.