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1.
Pharmacol Res ; 177: 106050, 2022 03.
Article in English | MEDLINE | ID: mdl-34973468

ABSTRACT

Sorafenib is a clinically useful multiple kinase inhibitor for the treatment of kidney cancer, liver cancer and acute myelocytic leukemia, while it has shown weak efficacy in suppressing breast cancer. Since sirtuin2 (SIRT2) is an important epigenetic regulator and associated with several cancer types including breast cancer, development and evaluation of new SIRT2 inhibitors to probe their therapeutic potentials is currently desirable. A highly selective SIRT2 inhibitor named I was previously developed by us, which showed activity to inhibit non-small cell lung cancer cell lines in vitro. We herein report expanded screening of I and its structurally similar inactive compound II against other cancer cell lines, and found that I had a wide spectrum of anticancer activity while II had no such effects. The I-sorafenib combination treatment exerted obvious synergistic reduction on cell viability of MCF-7 cells. We observed that the combination treatment could suppress cell proliferation, survival and migration, arrest cell cycle at G0/G1 phase, and induce apoptosis in MCF-7 cells, when compared with the single treatment. In vivo studies revealed that the combination treatment showed stronger tumor growth inhibition (87%), comparing with I-(42.8%) or sorafenib-solely-treated groups (61.1%) in MCF-7 xenograft model. In conclusion, this work clearly revealed a potential synthetic lethality effect for I combined with sorafenib, and will probably offer a new strategy at least for breast cancer treatment.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Cell Proliferation , Female , Humans , Lung Neoplasms/drug therapy , Niacinamide/pharmacology , Niacinamide/therapeutic use , Phenylurea Compounds/pharmacology , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Sirtuin 2 , Sorafenib/pharmacology , Sorafenib/therapeutic use , Synthetic Lethal Mutations , Xenograft Model Antitumor Assays
2.
Eur J Cardiovasc Nurs ; 19(7): 609-618, 2020 10.
Article in English | MEDLINE | ID: mdl-32338530

ABSTRACT

BACKGROUND: Sedentary behaviours may be related to factors such as self-efficacy, mood and social support. However, there is a paucity of longitudinal follow-up studies examining factors related to sedentary behaviour from physical-psychosocial perspectives in patients with heart failure. AIMS: The purpose of this study was to explore the multidimensional associated factors and impacts of sedentary behaviour in heart failure patients. METHODS: A longitudinal design was used. A convenience sample of 128 heart failure patients recruited from two large medical centres in northern Taiwan was obtained. Patients were interviewed with structured questionnaires to assess physical activity, symptom distress, exercise self-efficacy, anxiety and depression, social support, sleep quality and quality of life before discharge and at 3 and 6 months after discharge. RESULTS: Heart failure patients reported low physical activity and tended to be sedentary. Sedentary behaviour was gradually reduced from hospitalization to 6 months after discharge. Sleep quality, quality of life, analgesic use, symptom distress and exercise self-efficacy were significant associated factors that explained 42.1-51% of the variance in sedentary behaviour. Patients with high sedentary behaviour had significantly greater depression and poorer sleep and quality of life than those with low sedentary behaviour at hospitalization and showed a significant improvement in depression at 3 and 6 months after discharge. CONCLUSION: Sedentary behaviour is common in heart failure patients and has impacts on depression and quality of life. An appropriate physical activity programme focusing on disease self-management and enhancing self-efficacy is needed for heart failure patients to improve their sedentary behaviour and quality of life.


Subject(s)
Exercise/psychology , Heart Failure/psychology , Quality of Life/psychology , Risk Assessment/methods , Sedentary Behavior , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Male , Middle Aged , Surveys and Questionnaires , Taiwan
3.
J Clin Nurs ; 27(3-4): 876-882, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29076613

ABSTRACT

AIMS AND OBJECTIVES: To investigate the relationship of nurse practitioners' social support as well as other factors associated with perceived self-efficacy. BACKGROUND: There is a growing demand for nurse practitioners in Taiwan, for whom self-perceived efficacy is associated with performance. Nevertheless, research on the self-efficacy and social support of nurse practitioners is limited. DESIGN: This is a cross-sectional survey study. METHODS: Questionnaires were distributed to nurse practitioners in seven hospitals in northern Taiwan from May 2015 to March 2016. In total, data from 335 (78% return rate) certified nurse practitioners were analysed. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS) and the Job Content Questionnaire (JCQ), and perceived self-efficacy was measured by the General Self-Efficacy Scale (GSE). Data were analysed by ANOVAs with post hoc test and multiple linear regression. RESULTS: The mean score for self-efficacy was 27.60 ± 6.17. Support scores were 11.574 ± 2.37 for supervisors, 12.795 ± 1.92 for coworkers and 64.07 ± 10.16 for family, friends and significant others. nurse practitioners in the high monthly salary group had significantly higher self-efficacy than nurse practitioners in the medium and low monthly salary group (F = 8.99; p < .01). Social support from coworkers (ß = 0.18, p < .01) and family, friends and significant others (ß = 0.15, p < .01) and a higher monthly salary were significant factors. CONCLUSIONS: The self-efficacy of nurse practitioners in hospitals in Taiwan is insufficient. Monthly salary and levels of social support were found to contribute to nurse practitioners' self-efficacy. Thus, to enhance nurse practitioners' self-efficacy and work performance, nursing leaders should address these issues. RELEVANCE TO CLINICAL PRACTICE: The findings inform hospital administrators to be aware of the importance of salary in relation to nurse practitioners' perceptions of social support and self-efficacy.


Subject(s)
Nurse Practitioners/psychology , Self Efficacy , Social Support , Adult , Critical Care Nursing , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Salaries and Fringe Benefits/classification , Surveys and Questionnaires , Taiwan
4.
Can J Physiol Pharmacol ; 95(7): 811-818, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28177667

ABSTRACT

Accumulating lines of evidence indicate that high leptin levels are associated with adverse cardiovascular health in obese individuals. Proatherogenic effects of leptin include endothelial cell activation and vascular smooth muscle cell proliferation and migration. Ursolic acid (UA) has been reported to exhibit multiple biological effects including antioxidant and anti-inflammatory properties. In this study, we investigated the effect of UA on leptin-induced biological responses in rat vascular smooth muscle cells (VSMCs). A-10 VSMCs were treated with leptin in the presence or absence of UA. Intracellular reactive oxygen species (ROS) was probed by 2',7'-dichlorofluorescein diacetate. The expression of extracellular signal-regulated kinase (ERK)1/2, phospho-(ERK)1/2, nuclear factor-kappa B (NF-κB) p65 and p50, and matrix metalloproteinase-2 (MMP2) was determined by Western blotting. Immunocytochemistry and confocal laser scanning microscopy were also used for the detection of NF-κB. The secretion of MMP2 was detected by gelatin zymography. UA exhibited antioxidant activities in vitro. In rat VSMCs, UA effectively inhibited cell growth and the activity of MMP2 induced by leptin. These suppressive effects appeared by decreasing the activation of (ERK)1/2, the nuclear expression and translocation of NF-κB, and the production of ROS. UA appeared to inhibit leptin-induced atherosclerosis, which may prevent the development of obesity-induced cardiovascular diseases.


Subject(s)
Antioxidants/pharmacology , Leptin/pharmacology , Muscle, Smooth, Vascular/cytology , Triterpenes/pharmacology , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Enzymologic/drug effects , Matrix Metalloproteinase 2/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , NF-kappa B p50 Subunit/metabolism , Phosphoproteins/metabolism , Rats , Reactive Oxygen Species/metabolism , Transcription Factor RelA/metabolism , Ursolic Acid
5.
Can J Physiol Pharmacol ; 94(6): 627-33, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26991492

ABSTRACT

The metabolic disturbance of obesity is one of the most common risk factors of atherosclerosis. Resistin, an obesity-induced adipokine, can induce the expression of cell adhesion molecules and the attachment of monocytes to endothelial cells, which play an important role in the development of atherosclerosis. Ursolic acid, a pentacyclic triterpenoid found in fruits and many herbs, exhibits an array of biological effects such as anti-inflammatory and antioxidative properties. The aim of this study was to investigate the potential underlying mechanisms of the effect of ursolic acid on resistin-induced adhesion of U937 cells to human umbilical vein endothelial cells (HUVECs). Our data indicated that ursolic acid suppressed the adhesion of U937 to HUVECs and downregulated the expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and E-selectin, in resistin-induced HUVECs by decreasing the production of intracellular reaction oxygen species (ROS) and attenuating the nuclear translocation of NFκB. Ursolic acid appeared to inhibit resistin-induced atherosclerosis, suggesting that ursolic acid may play a protective role in obesity-induced cardiovascular diseases.


Subject(s)
Cardiotonic Agents/pharmacology , Cardiovascular Diseases/metabolism , Endothelium, Vascular/drug effects , Obesity/metabolism , Triterpenes/pharmacology , Cardiotonic Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/etiology , Cell Adhesion/drug effects , Cell Adhesion/physiology , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Dose-Response Relationship, Drug , Endothelium, Vascular/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Monocytes/drug effects , Monocytes/metabolism , Obesity/complications , Obesity/drug therapy , Triterpenes/therapeutic use , U937 Cells , Ursolic Acid
6.
J Food Drug Anal ; 24(3): 556-563, 2016 07.
Article in English | MEDLINE | ID: mdl-28911561

ABSTRACT

Atherosclerosis plays a key role in the development of cardiovascular diseases, and is often associated with oxidative stress and local inflammation. Thymol, a major polyphenolic compound in thyme, exhibits antioxidant and anti-inflammatory properties. In this study, we measured the in vitro antioxidant activity of thymol, and investigated the effect of thymol on high-fat-diet-induced hyperlipidemia and atherosclerosis. New Zealand white rabbits were fed with regular chow, high-fat and high-cholesterol diet (HC), T3, or T6 (HC with thymol supplementation at 3 mg/kg/d or 6 mg/kg/d, respectively) for 8 weeks. Aortic intimal thickening, serum lipid parameters, multiple inflammatory markers, proinflammatory cytokines, and atherosclerosis-associated indicators were significantly increased in the HC group but decreased upon thymol supplementation. In summary, thymol exhibits antioxidant activity, and may suppress the progression of high-fat-diet-induced hyperlipidemia and atherosclerosis by reducing aortic intimal lipid lesion, lowering serum lipids and oxidative stress, and alleviating inflammation-related responses.


Subject(s)
Oxidative Stress , Animals , Antioxidants , Gene Expression , Hypercholesterolemia , Inflammation , Rabbits , Thymol
7.
Br J Nutr ; 113(6): 975-83, 2015 Mar 28.
Article in English | MEDLINE | ID: mdl-25746049

ABSTRACT

Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother-offspring cohort were assayed at 26-28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.


Subject(s)
Child Development , Fatty Acids, Omega-3/therapeutic use , Fatty Acids, Omega-6/therapeutic use , Fetal Development , Hypersensitivity/prevention & control , Lactation , Maternal Nutritional Physiological Phenomena , Adult , Cohort Studies , Eczema/etiology , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/adverse effects , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-6/administration & dosage , Fatty Acids, Omega-6/adverse effects , Fatty Acids, Omega-6/blood , Female , Follow-Up Studies , Humans , Hypersensitivity/epidemiology , Hypersensitivity/etiology , Hypersensitivity/physiopathology , Infant, Newborn , Male , Pregnancy , Pregnancy Trimester, Second/blood , Prevalence , Prospective Studies , Respiratory Sounds/etiology , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/etiology , Rhinitis, Allergic/physiopathology , Rhinitis, Allergic/prevention & control , Risk , Singapore/epidemiology , Skin Tests
8.
J Nutr Sci Vitaminol (Tokyo) ; 58(5): 309-18, 2012.
Article in English | MEDLINE | ID: mdl-23327965

ABSTRACT

Vitamin A is a key micronutrient required during crucial stages of embryonic development and vitamin A deficiency (VAD) results in embryonic heart malformation. The pleiotropic functions of vitamin A are mediated by specific nuclear receptors: the retinoic acid receptors (RARα, -ß, and -γ) and the retinoic X receptors (RXRα, -ß, and -γ). The action of nuclear receptors has been implicated in controlling of cell proliferation, differentiation and apoptosis, and the expressions of these receptor genes are regulated by retinoic acid levels during the early stages of embryonic development. GATA-4 is one of the earliest transcription factors expressed in developing cardiac cells. However, the functional links of specific nuclear receptors to heart development in VAD embryos are not clearly understood. In our study, weaning female Sprague-Dawley rats were fed a modified diet containing different concentrations of vitamin A according to the American Institute of Nutrition 93 Growth Purified Diet. After 10-wk feeding, the female rats were mated with normal male rats, and a portion of them were transferred to a diet with enough added vitamin A for the pregnancy cycle. The embryo hearts were dissected out at embryonic day 13.5 (E13.5) to study the expression of RARs, RXRs and GATA-4. The embryo hearts from E18.5 were for observation of ultrastructural changes. In comparison to vitamin A supplemented groups, the embryo hearts from vitamin A insufficient groups exhibited ultrastructural changes and significantly lower expression of GATA-4, RARα, and -γ, and higher expression of RXRα and -ß. Our findings suggest that the down-regulation of RARs and the up-regulation of RXRs resulted from VAD affected GATA-4 gene expression, which resulted in ultrastructural changes in embryo hearts due to maternal insufficiency of vitamin A during pregnancy.


Subject(s)
GATA4 Transcription Factor/metabolism , Heart/embryology , Maternal Nutritional Physiological Phenomena , Receptors, Retinoic Acid/metabolism , Vitamin A Deficiency/embryology , Vitamin A/administration & dosage , Animals , Cell Differentiation , Dietary Supplements , Down-Regulation , Female , GATA4 Transcription Factor/genetics , Heart/physiopathology , Immunohistochemistry , Male , Microscopy, Electron, Transmission , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, Retinoic Acid/genetics , Retinoid X Receptors/genetics , Retinoid X Receptors/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Up-Regulation
9.
Arch Dermatol Res ; 302(10): 717-24, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20717830

ABSTRACT

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) in the dermis. It is a late spreading skin overgrowth and may be considered a plastic surgeon's nightmare. In nature, curcuminoid is composed of curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (bDMC). Curcuminoids have been found to inhibit fibrosis. However, their role in the synthesis of ECM in the keloid fibroblasts (KFs) has remained unclear. In this series of studies, a total of seven primary KFs cultures were used as the KFs model for investigating the inhibitory effect of curcuminoids on the expression of ECM and TGF-ß1. A sensitive and reproducible HPLC method was developed to provide a quantitative analysis on the cellular uptake of curcuminoids onto the KF cells. The level of ECM in the primary KFs was elevated. The elevation of ECM and TGF-ß1/p-SMAD-2 level was substantially blocked by the cellular uptake of curcumin in a dose-dependent manner in all the seven primary KFs. The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin.


Subject(s)
Curcumin/pharmacology , Fibroblasts/drug effects , Keloid/drug therapy , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism , Adult , Aged , Cell Culture Techniques , Cells, Cultured , Chromatography, High Pressure Liquid , Curcumin/analogs & derivatives , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Female , Fibroblasts/immunology , Fibroblasts/metabolism , Fibroblasts/pathology , Humans , Keloid/genetics , Keloid/metabolism , Keloid/pathology , Male , Middle Aged , Signal Transduction/drug effects , Smad Proteins/genetics , Transforming Growth Factor beta/genetics , Up-Regulation/drug effects
10.
Eur J Nutr ; 49(5): 267-75, 2010 Aug.
Article in English | MEDLINE | ID: mdl-19937041

ABSTRACT

BACKGROUND: Expression of cell adhesion molecules (CAM) on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. Chlorogenic acid is a phenolic compound present in coffee, apples, pears, berries, almonds, artichokes, and aubergines. Previous studies have indicated that CA possesses antioxidant activity in vitro. AIM: We investigated the effects of chlorogenic acid and probucol on monocyte-like adhesion, adhesion molecule expression, NF-kappaB translocation and ROS production in IL-1beta-induced human umbilical vein endothelial cells (HUVECs). RESULTS: According to the results of the MTT assay, we chose 25 and 50 mumol/L to perform the experiments. Chlorogenic acid dose-dependently suppressed IL-1beta-induced mRNA expression of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1 and endothelial cell selectin. Chlorogenic acid also suppressed the IL-1beta-induced production of ROS. We also observed that chlorogenic acid attenuated or blocked IL-1beta-induced nuclear translocation of nuclear factor-kappaB subunits p50 and p65, which in turn attenuated CAM expression at the transcription level. Furthermore, chlorogenic acid significantly reduced the adhesion of human monocyte cells (U937) to IL-1beta-treated HUVECs in a dose-response manner. These results are similar to that of probucol. CONCLUSIONS: We conclude that chlorogenic acid exhibit anti-inflammatory effects in HUVECs by inhibition of U937 monocyte-like adhesion, adhesion molecule expression, NF-kappaB translocation, and ROS production. The anti-inflammatory activity of chlorogenic acid in HUVECs suggests that chlorogenic acid could be useful in the prevention of atherosclerosis.


Subject(s)
Cell Adhesion Molecules/genetics , Chlorogenic Acid/pharmacology , Endothelial Cells/metabolism , Interleukin-1beta/pharmacology , Up-Regulation/drug effects , Antioxidants/pharmacology , Cell Adhesion/drug effects , Cell Line , Cells, Cultured , E-Selectin/genetics , Endothelial Cells/drug effects , Gene Expression/drug effects , Humans , Intercellular Adhesion Molecule-1/genetics , Monocytes/physiology , NF-kappa B/antagonists & inhibitors , Probucol/pharmacology , RNA, Messenger/analysis , Reactive Oxygen Species/antagonists & inhibitors , Umbilical Veins/cytology , Vascular Cell Adhesion Molecule-1/genetics
11.
Eur J Nutr ; 48(2): 101-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19142568

ABSTRACT

BACKGROUND: Expression of cell adhesion molecules on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. AIM OF THE STUDY: We investigated the effects of carnosic acid on the adhesion of U937 cells to IL-1beta-treated human umbilical vein endothelial cells (HUVECs), as well as on the expression of adhesion molecules. RESULTS: Our data showed that pretreatment with 10 and 20 micromol/l carnosic acid significantly reduced the number of U937 cells adhering to IL-1beta-treated HUVECs. In addition, we found that 20 micromol/l carnosic was more effective than 10 micromol/l carnosic acid at inhibiting expression of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin), the nuclear translocation of NF-kappaB subunits p65 and p50, and the production of ROS in IL-1beta-stimulated HUVECs. CONCLUSIONS: We conclude that carnosic acid inhibits IL-1beta-induced ICAM-1, VCAM-1 and E-selectin expression in HUVECs through a mechanism that involves NFkappaB. We propose that the reduction in binding of human monocytic cell line U937 to IL-1beta-treated HUVECs is due to the anti-inflammatory properties of carnosic acid.


Subject(s)
Abietanes/pharmacology , Cell Adhesion Molecules/analysis , Cell Adhesion/drug effects , Endothelial Cells , Interleukin-1beta/pharmacology , Monocytes/physiology , Plant Extracts/pharmacology , Cell Survival/drug effects , E-Selectin/analysis , Humans , Intercellular Adhesion Molecule-1/analysis , NF-kappa B/metabolism , Reactive Oxygen Species/antagonists & inhibitors , U937 Cells , Umbilical Veins/cytology , Vascular Cell Adhesion Molecule-1/analysis
12.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 5): m576, 2009 Apr 25.
Article in English | MEDLINE | ID: mdl-21583804

ABSTRACT

The title compound, [Zn(C(8)H(4)O(4))(C(5)H(8)N(2))(3)], has a neutral monomeric structure in which one terephthalate dianion and three 2-ethyl-1H-imidazole ligands coordinate to the Zn(II) ion in a distorted tetra-hedral geometry. The methyl group of one of the ethyl groups is disordered over two positions with occupancies of 0.66 (2) and 0.34 (2). In the crystal structure, mol-ecules are linked into a three-dimensional hydrogen-bonded network by inter-molecular N-H⋯O interactions involving the uncoordinated carboxyl-ate O atoms.

13.
Br J Nutr ; 100(4): 731-8, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18298869

ABSTRACT

The migration and matrix metalloproteinase (MMP) activation of vascular smooth muscle cells may play key roles in the development of atherosclerosis. Carnosic acid (CA) is a phenolic compound found in herbs, including rosemary and sage. Previous studies indicated that CA possesses antioxidant activity in vitro. In this study, we investigated the effects of CA on TNF-alpha-induced cell migration, the formation of intracellular reactive oxygen species, the translocation of NF-kappaB and the activation and expression of MMP-9 in human aortic smooth muscle cells (HASMC). The Matrigel migration assay showed that CA (10 and 20 micromol/l) effectively inhibited TNF-alpha-induced migration of HASMC as compared with the control group. To explain this inhibitory effect, MMP-9 was assayed by gelatin zymography and Western blot. The results indicated that CA inhibited MMP-9 activity and expression. Furthermore, the production of reactive oxygen species and the nuclear translocation of NF-kappaB p50 and p65 induced by TNF-alpha were dose-dependently suppressed by CA pretreament. These results indicate that CA has anti-inflammatory properties and may prevent the migration of HASMC by suppressing MMP-9 expression through down-regulation of NF-kappaB.


Subject(s)
Abietanes/pharmacology , Antioxidants/pharmacology , Matrix Metalloproteinase 9/metabolism , Myocytes, Smooth Muscle/drug effects , Plant Extracts/pharmacology , Salvia miltiorrhiza , Abietanes/chemistry , Analysis of Variance , Antioxidants/chemistry , Aorta , Atherosclerosis/metabolism , Cell Movement/drug effects , Cells, Cultured , Depression, Chemical , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Gene Expression , Humans , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/genetics , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/enzymology , NF-kappa B/metabolism , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/pharmacology
14.
Br J Nutr ; 99(4): 709-14, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18184451

ABSTRACT

Proliferation of intimal vascular smooth muscle cells is an important component in the development of atherosclerosis. Ellagic acid is a phenolic compound present in fruits (raspberries, blueberries, strawberries) and walnuts. The present study investigated the effect of ellagic acid on the oxidised LDL (ox-LDL)-induced proliferation of rat aortic smooth muscle cells (RASMC). The study found that ellagic acid significantly inhibited ox-LDL-induced proliferation of RASMC and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Furthermore, ellagic acid also blocked the ox-LDL-induced (inducible) cell-cycle progression and down regulation of the expression of proliferating cell nuclear antigen (PCNA) in RASMC. Therefore, ellagic acid reduced the amount of ox-LDL-induced proliferation of RASMC via inactivation of the ERK pathway and suppression of PCNA expression. These results may significantly advance the understanding of the role that antioxidants play in the prevention of atherosclerosis.


Subject(s)
Antioxidants/pharmacology , Ellagic Acid/pharmacology , Mitogen-Activated Protein Kinase 3/metabolism , Myocytes, Smooth Muscle/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Animals , Aorta , Biomarkers/analysis , Blotting, Western/methods , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Enzyme Activation/drug effects , Flow Cytometry , Humans , Lipoproteins, LDL/metabolism , Lipoproteins, LDL/pharmacology , Mitogen-Activated Protein Kinase 3/analysis , Myocytes, Smooth Muscle/drug effects , Phosphorylation , Proliferating Cell Nuclear Antigen/analysis , Rats
15.
Protein Pept Lett ; 14(8): 836-8, 2007.
Article in English | MEDLINE | ID: mdl-17979829

ABSTRACT

The thrC gene of Streptococcus mutans encodes threonine synthase, which is a potential target for drug design. To study the structure and function of the enzyme, the thrC gene was amplified from Streptococcus mutans genomic DNA and cloned into the expression vector pET28alpha. The protein was expressed in Escherichia coli in soluble form and purified to homogeneity. Crystals suitable for X-ray diffraction were obtained by hanging-drop vapor diffusion method. The crystal diffracted to 2.5 A and belonged to space group P3(1) or P3(2), with unit cell parameters a=b=60.39 A, c=118.62 A.


Subject(s)
Carbon-Oxygen Lyases/chemistry , Carbon-Oxygen Lyases/isolation & purification , Streptococcus mutans/enzymology , Amino Acid Sequence , Crystallization , Crystallography, X-Ray , Escherichia coli/metabolism , Molecular Sequence Data , Sequence Alignment
16.
Br J Nutr ; 97(4): 692-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17349082

ABSTRACT

Expression of cell adhesion molecules by endothelium and the attachment of monocytes to endothelium may play a major role in atherosclerosis. Ellagic acid (EA) is a phenolic compound found in fruits and nuts including raspberries, strawberries, grapes and walnuts. Previous studies have indicated that EA possesses antioxidant activity in vitro. In the present study, we investigated the effects of EA on the formation of intracellular reactive oxygen species, the translocation of NFkappaB and expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 and endothelial leucocyte adhesion molecule (E-selectin) induced by IL-1beta in human umbilical vein endothelial cells (HUVEC). We found that EA significantly reduced the binding of human monocytic cell line, U937, to IL-1beta-treated HUVEC. The production of reactive oxygen species by IL-1beta was dose-dependently suppressed by EA. Supplementation with increasing doses of EA up to 50 micromol/l was most effective in inhibiting the expression of VCAM-1 and E-selectin. Furthermore, the inhibition of IL-1beta-induced adhesion molecule expression by EA was manifested by the suppression of nuclear translocation of p65 and p50. In conclusion, EA inhibits IL-1beta-induced nuclear translocation of p65 and p50, thereby suppressing the expression of VCAM-1 and E-selectin, resulting in decreased monocyte adhesion. Thus, EA has anti-inflammatory properties and may play an important role in the prevention of atherosclerosis.


Subject(s)
Cell Adhesion Molecules/biosynthesis , Ellagic Acid/pharmacology , Endothelium, Vascular/drug effects , Interleukin-1beta/antagonists & inhibitors , Cell Adhesion/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , E-Selectin/metabolism , Endothelium, Vascular/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Interleukin-1beta/pharmacology , Reactive Oxygen Species/metabolism , U937 Cells , Umbilical Veins/drug effects , Umbilical Veins/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
17.
J Cardiovasc Pharmacol ; 47(3): 463-8, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16633091

ABSTRACT

Oxidative stress and apoptosis are 2 major characteristics of the progression of atherosclerosis. Both lovastatin and Magnolia officinalis are hypocholesterolemic agents. Therefore, we investigated the effect of M. officinalis extract on the prevention of atherosclerosis in comparison with lovastatin. Twenty hyperlipidemic rabbits were served one of the following diets: a high-fat and cholesterol diet (cholesterol group, 10% corn oil and 0.5% cholesterol), a high fat and cholesterol diet supplemented with M. officinalis extract (300 mg/kg) or lovastatin (6 mg/kg). The plasma lipids, oxidative stress (measured by free radical, malondialdehyde, and oxidative DNA damage), and arterial lesions significantly decreased in the M. officinalis and lovastatin groups when compared with the cholesterol group. Moreover, the expressions of Fas ligand, caspase 8, and caspase 9 in the aortic arches were also markedly lowered after M. officinalis and lovastatin supplements. Therefore, the results indicate that the antiatherogenic effect of M. officinalis is involved with a suppression of oxidative stress and with the down-regulation of apoptosis-related gene expression in hyperlipidemic rabbits.


Subject(s)
Aorta, Thoracic/drug effects , Apoptosis/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hyperlipidemias/drug therapy , Lovastatin/pharmacology , Magnolia , Oxidative Stress/drug effects , Plant Extracts/pharmacology , 8-Hydroxy-2'-Deoxyguanosine , Animals , Aorta, Thoracic/metabolism , Aorta, Thoracic/pathology , Caspase 8 , Caspase 9 , Caspases/genetics , Cholesterol/blood , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Fas Ligand Protein , Gene Expression Regulation/drug effects , Hyperlipidemias/metabolism , Hyperlipidemias/pathology , Malondialdehyde/blood , Membrane Glycoproteins/genetics , Rabbits , Tumor Necrosis Factors/genetics
18.
J Nutr Biochem ; 16(11): 675-81, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16081267

ABSTRACT

Oxidative stress is one of the major risk factors for coronary artery disease. Ellagic acid is a phenolic compound present in fruits and nuts, and has been found to have antioxidative property. Twenty-four New Zealand white (NZW) rabbits were assigned randomly into four dietary groups. The normal group was fed regular rabbit chow, and the cholesterol group was fed a high fat and cholesterol diet. The ellagic acid (E) group and probucol group were fed the same diet as the cholesterol group plus the addition of 1% (w/w diet) ellagic acid and probucol, respectively. Oxidative stress [as measured by plasma lipids, oxygen free radicals and thiobarbituric acid reactive substances (TBARS)] increased in the cholesterol group compared with the normal group; however, it decreased in the probucol and E groups compared with the cholesterol group. Forty-five percent of the intimal surface of the thoracic aorta was covered with atherosclerotic lesions in the cholesterol group, but only 2-3% was covered in the E and probucol groups. The aortic level of 8-(OH)dG and the expression of caspase-8, caspase-9 and Fas ligand were also suppressed after ellagic acid supplement. These results indicated that ellagic acid could prevent atherosclerosis via suppression of oxidative stress and apoptosis in hyperlipidemic rabbits.


Subject(s)
Apoptosis/drug effects , Ellagic Acid/pharmacology , Hyperlipidemias/drug therapy , Oxidative Stress/drug effects , 8-Hydroxy-2'-Deoxyguanosine , Animals , Anticholesteremic Agents/pharmacology , Antioxidants/pharmacology , Aorta, Thoracic/pathology , Atherosclerosis/prevention & control , Caspase 8 , Caspase 9 , Caspases/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Fas Ligand Protein , Free Radical Scavengers/metabolism , Hyperlipidemias/metabolism , Hyperlipidemias/pathology , Lipids/blood , Membrane Glycoproteins/metabolism , Probucol/pharmacology , Rabbits , Thiobarbituric Acid Reactive Substances/metabolism , Tumor Necrosis Factors/metabolism
19.
Can J Physiol Pharmacol ; 83(5): 423-30, 2005 May.
Article in English | MEDLINE | ID: mdl-15897924

ABSTRACT

Hyperlipidemia may induce oxidative stress, which is important in the pathogenesis of atherosclerosis. Dioscorea rhizome (DR) is the powdered form of yams, and possesses antioxidant and hypolipidemic function. We therefore investigated the antioxidative and antiatherogenic effects of DR on hyperlipidemic rabbits. The control group was fed chow containing 0.5% cholesterol and 10% corn oil. The probucol and DR groups were fed the same diet as the control group but with the addition of 100 mg probucol/kg chow and 200 mg DR/kg chow, respectively. Total cholesterol and triacylglycerol plasma levels, RBC hemolysis T50, lucigenin chemiluminescence, and luminol chemiluminescence increased in the control group compared with the normal group, and decreased in the probucol and DR groups compared with the control group. The activity of antioxidant enzymes superoxide dismutase and catalase was significantly higher in the probucol and DR group than in the control group. The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver DNA was lower in the probucol and DR group than in the control group. Eighty percent of the intimal surface of the thoracic aorta was covered with atherosclerotic lesions in the control group but only 40% of the surface was covered in the DR group. These results suggest that supplementation with DR reduces oxidative stress and attenuates atherosclerosis in hyperlipidemic rabbits.


Subject(s)
Anticholesteremic Agents/pharmacology , Antioxidants/pharmacology , Atherosclerosis/prevention & control , Dioscorea , Hyperlipidemias/drug therapy , Liver/drug effects , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/pharmacology , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/pathology , Atherosclerosis/pathology , Catalase/metabolism , Dietary Fats , Free Radicals/blood , Free Radicals/metabolism , Glutathione Peroxidase/metabolism , Hemolysis/drug effects , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Lipids/blood , Liver/enzymology , Luminescent Measurements , Male , Probucol/pharmacology , Rabbits , Rhizome/chemistry , Superoxide Dismutase/metabolism
20.
Biol Pharm Bull ; 27(6): 802-5, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15187421

ABSTRACT

Forty hyperlipidemic patients, smokers and non-smokers, were studied. Subjects received 15 g young barley leaf extract (BL) or 60 g adlay daily for four weeks. Overnight fasting blood samples were drawn immediately prior to and after four weeks of supplementation. Blood samples were analyzed for plasma lipid profiles and their susceptibility to low-density lipoprotein (LDL) oxidation. The plasma total and LDL-cholesterol (LDL-C) levels were reduced following treatment with either BL or adlay; furthermore, the lag phase of LDL oxidation increased after either supplementation. However, it seemed that BL had stronger antioxidative effect on the prevention of LDL oxidation than adlay. Our results also indicated that the antioxidative effect was less pronounced in smokers than in non-smokers. Therefore, supplementation with BL or adlay can decrease plasma lipids and inhibit LDL oxidation in hyperlipidemic smokers and/or non-smokers.


Subject(s)
Coix , Hordeum , Hyperlipidemias/blood , Lipids/blood , Lipoproteins, LDL/blood , Smoking/blood , Adult , Aged , Analysis of Variance , Humans , Hyperlipidemias/drug therapy , Male , Middle Aged , Oxidation-Reduction/drug effects , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Leaves , Smoking/drug therapy
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