Korean red ginseng (KRG) has been shown to enhance endothelium-dependent vasorelaxation in experimental animals; however, little is known about its pharmacological effects on vascular stiffness in patients with coronary artery disease (CAD). This randomized, double-blind, placebo-controlled crossover trial was carried out to determine whether KRG has beneficial effects on arterial stiffness, cardiovascular risk factors such as plasma lipid profiles and blood pressure (BP), and Rho-associated kinase (ROCK) activity. Twenty patients (mean age, 62.5 years) with stable angina pectoris were given KRG (2.7 g/day) and a placebo alternatively for 10 weeks. Blood biochemical analysis and pulse wave velocity (PWV) recording were performed on day 0 and after the completion of each treatment. ROCK activity was assessed based on the level of phospho-$Thr^{853}$ in the myosin-binding subunit of myosin light chain phosphatase, determined by Western blot analysis of peripheral blood mononuclear cells. KRG significantly decreased the systolic BP, brachial ankle PWV, and heart femoral PWV in the patients (all p<0.05), but did not significantly alter the serum lipid profiles, including triglycerides and total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. The ROCK activity tended to decrease (p=0.068) following KRG treatment. The placebo did not significantly alter any of the variables. In conclusion, KRG decreased systolic BP and arterial stiffness, probably via the inhibition of ROCK activity, in patients with CAD, but had a neutral effect on serum lipid profiles. Our data suggest that KRG has a therapeutic effect on CAD.
To determine the correlation between mast cells(MCs) and neoangiogenesis in the growth and progression of cervical cancer, we investigated mast cell density(MCD), microvessel density(MVD) and the expression of vascular epithelial growth factor(VEGF) in cervical intraepithelial neoplasia and invasive suqamous cell carcinoma of the uterine cervix. Forty-five cervical intraepithelial neoplasia(CIN I, II and III), 15 microinvasive carcinomas, 15 invasive squamous cell carcinomas and 20 normal cervical epithelia were included in this study. MCs were stained with anti-c-Kit antibody and alcian blue, microvessels with anti-factor VIII antibody and VEGF with anti-VEGF antibody. The adjacent fields of both normal and neoplastic epithelium were used for counting MCs and microvessels. Computerized image analysis was used to evaluate MCD and MVD. MCD and MVD were the mean numbers per $1mm^2$ counted in 5-10 high and low power fields respectively. In both c-Kit and alcian blue stained sections, MCD progressively increased along the continuum from CIN I to invasive squamous cell carcinoma(p<0.001). MVD increased significantly with cervical neoplasia progression, from CIN to invasive squamous cell carcinoma (p<0.001). In double c-Kit and Factor VIII-stained sections, MCs were mainly present in the areas adjacent to newly formed blood vessels. However, there were no significant differences in MCD and MVD between normal epithelum and CIN I. A strong correlation was also observed between MCD and MVD. In double VEGF and alcian blue-stained sections, VEGF was expressed in only MCs. Strong VEGF-positive MCs were particularly abundant around the tumorous region. Our results suggest that MCs may upregulate neoangiogenesis by VGEF secretion in the development and progression of cervical neoplasia.
Kim, Dong-Ik;Park, Hee-Jung;Eo, Hyun-Seoun;Suh, Soo-Won;Hong, Ji-Hee;Lee, Min-Jae;Kim, Jong-Sung;Jang, In-Sung;Kim, Byung-Soo
Journal of Microbiology and Biotechnology
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제14권4호
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pp.707-714
/
2004
How to improve the cell culture method on scaffolds is important in the tissue engineering fileld. In this study, we optimized seeding and culture methods to vascular smooth muscle cells (VSMCs) on biodegradable polymer scaffold. The primary culture of VSMCs obtained from canine external jugular vein was accomplished by applying the explant-derived method. The primary cultured VSMCs were seeded into scaffolds and then cultured by using various different methods; static or dynamic seeding, static or dynamic culture. The difference in proliferative response of VSMCs was analyzed with an alamar blue assay. Cell-polymer construct was examined by histochemical method and scanning electron microscopy. Mesh type scaffold ($10 \times 10 \times0.4 mm$) was made of polyglycolic acid (PGA) suture thread. The PGA mesh type scaffold was 45% in porosity, and 0.03 g in weight. The primary cultured VSMCs were confirmed with immunohistochemical staining using monoclonal anti-$\alpha$-smooth muscle actin. The density and distribution of proliferated VSMCs within the scaffold and cellular adherence on the surface of the scaffold showed better results in the static seeding condition than in the dynamic condition. Under the same condition of seeding method as the static condition, the dynamic culture condition showed enhanced proliferation rates of the VSMCs when compared to the static culture condition. In conclusion, to improve the VSMCs proliferation in vitro, static seeding is better than the dynamic condition. In the culture condition, however, culture under the dynamic status is better than the static condition. This was a pilot study to manufacture artificial vascular vessel by tissue engineering.
Vascular changes in the periodontal ligament of the rat incisors following application of experimental orthodontic forces were examined by the India ink perfusion method. 57 rats were used for this experiment. The rats were divided into experimental group (54 rats) and control group (3 rats). 54 experimental rats were divided into group I (27 rats) and group II (27 rats). The right and left upper incisors of group. I and group II rats were separated distally with forces of 20gm, 70gm respectively. The vascular changes of periodontal ligament were observed histologically by means of light microscope after 1, 2 and 3 days of tooth movement and 1,3,5,8,14, and 21 days after removal of orthodontic force. The results were as follows; 1. After one day of tooth movement, occlusion of blood vessels, hyalinization of periodontal ligament and resorption of alveolar bone adjacent to the alveolar crest on pressure side were observed. Above the tissue changes on the pressure side of group II were more severe than those of group I. Especially, septal bone of group II was separated after 2 days of tooth movement. 2. In tension zones, periodontal space was widened and periodontal fibers were orientated in the direction of puil. The blood vessels of periodontal ligament were distended. New bone deposition was seen along the inner surface of the alveolus after 2 days of tooth movement. 3. After 3 days of tooth movement, deposition of new bone was seen along the periosteal surface of alveolar bone on pressure side, progressing with increasing after removal of orthodontic force. Remodelling of the new bone was occurred 5 days after removal of orthodontic force. 4. 3 days after removal of orthodontic force, invasion of blood vessels into the marginal periodontal ligament on pressure side was observed clearly and the vessels below the epithelial attachment were increased. 5. After removal of orthodontic force, hyalinized structures disappeared concomittantly with an invasion of blood vessels from the neighboring periodontal ligament. 14 days after removal of orthodontic force, the vessels in the periodontal ligament of group I were finished the vascular rearrangement. 21 days after removal of orthodontic force, the vessels in the periodontal ligament of group II were finished the vascular rearrangement.
Cirsium japonicum water extracts has been used to treat vascular related diseases. We have previously reported that Cirsium japonicum extracts activated estrogen receptors. It is widely known that estrogen increases the high density lipoprotein cholesterol and decrease the low density lipoprotein cholesterol on the lipid profile. But effects of Cirsium japonicum on lipid profile are not reported yet. Therefore, we have studied the effects of Cirsium japonicum on the lipid content in ovariectomized rats. Thirty Sprague-Dawley (SD) rats of $210{\pm}20\;g$ were studied for 10 weeks. The rats were divided into five groups; (I) sham, no ovariectomized rats plus olive oil, (II) ovariectomized rats plus olive oil, (III) ovariectomized rats plus 0.5 mg/kg $17{\beta}$-estradiol (E2) in olive oil, (IV) ovariectomized rats plus 0.5 mg/kg Cirsium japonicum in olive oil, and (V) ovariectomized rats plus 5 mg/kg Cirsium japonicum in olive oil. Treatment with Cirsium japonicum or E2 induced significant reduction in total cholesterol, low density lipoprotein cholesterol/total cholesterol, total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol compared to control group as well as increase in uterine weight. However, changes in triglycerides levels were different. Our results suggest that Cirsium japonicum is functionally similar to E2 in vivo as well as in vitro.
A crucial and causative role in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low density lipoprotein (LDL). The oxidation of LDL involves released free radical driven lipid peroxidation. Several lines of evidence support the role of oxidized LDL in atherogenesis. Epidemiologic studies have demonstrated an association between an increased intake of dietary antioxidant vitamins, such as vitamin E and vitamin C and reduced morbidity and mortality from coronary artery diseases. It is thus hypothesized that dietary antioxidants may help prevent the development and progression of atherosclerosis. The oxidation of LDL has been shown to be reduced by antioxidants, and, in animal models, improved antioxidants may offer possibilities for the prevention of atherosclerosis. The results of several on going long randomized intervention trials will provide valuahle information on the efficacy and safety of improved antioxidants in the prevention of atherosclerosis. This review a evaluates current literature involving antioxidants and vascular disease, with a particular focus on the potential mechanisms.
Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.
Objectives : In Korean medicine, a prescription of Sinsun-yukza-hwan (Shenxian-liuzi-wan, SSY) has been used in clinic for treatment of alopecia via oral. This study was performed to determine transdermal effects of the ethanol extract from SSY on hair growth and -related gene expressions in mice. Methods : We analyzed index compound, 5-hydroxy-methyl-2-furaldehyde (HMF), in SSY extract by ultra performance liquid chromatography (UPLC). 6 weeks old C57BL/6 mice with removed hair were used as an alopecia animal model. Mice were divided into 3 experimental groups including normal (3 water: 1 ethanol: 2 polyethylene glycol mixture as a vehicle), SSY extract and 5% minoxidil (as a positive control), treated groups. SSY was applied topically on the hair-shaved skin of C57BL/6 mice every day for 15 days. The color, thickness and density of hair were monitored every $5^{th}$ day by naked eye, photograph and phototrichogram using folliscope. Also hair growth-associated gene expressions were measured by immunoblotting assay. Results : Hair density of minoxidil or SSY-treated group was significantly increased compared to that of vehicle application on the $15^{th}$ day, respectively. And hair thickness of minoxidil and SSY groups was increased compared to that of vehicle treated group on the $15^{th}$ day, respectively. Induction of insulin-like-growth factor 1(IGF-1) and vascular endothelial growth factor (VEGF) were also significantly accelerated by SSY extract compared to those of vehicle-applied group. Conclusions : These results provide scientific evidence to support the potent multi-application of SSY as a cosmeceutical material for promoting hair growth.
Haggag, Basma S.;Hasanin, Amany H.;Raafat, Mona H.;Kawy, Hala S. Abdel
The Korean Journal of Physiology and Pharmacology
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제18권3호
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pp.269-278
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2014
Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.
Several polyphenolic compounds and complex mixtures were isolated from brown algae species. The 1,1-diphenyl-2-picryhydarzyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) of these compounds were evaluated to determine their physiological usefulness as antioxidants for vascular protection. The antioxidative protection of low-density lipoprotein (LDL) was also evaluated and compared with that of catechin, because the generation of oxidized LDL is one of the most active and specific risk factors contributing to atherogenesis. Oral administration to rats of a commercially available sample ($VNP^{TM}$) containing 30% of these polyphenolic compounds and 70% dietary fiber revealed that the serum reducing capacity measured in terms of FRAP value was significantly elevated 30 min after the treatment, but declined rather quickly thereafter, indicating the good oral absorption of the compounds and their fast binding to the lumenal surface of the blood vessels. An eight-week, human, clinical trial (n=31) of $VNP^{TM}$ showed significant improvement in erectile function measured by IIEF (international index of erectile function) score. These results collectively demonstrated the usefulness of these polyphenolic compounds as fundamental chemopreventive agents against vascular risk factors originating from oxidative stress.
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