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1.
Iran J Immunol ; 17(1): 64-74, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32224542

ABSTRACT

BACKGROUND: Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol. OBJECTIVE: To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L. (TT) on the proteome and expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the human umbilical vein endothelial cell (HUVEC) and human bone marrow endothelial cell (HBMEC) lines. METHODS: Two cell lines were cultured and induced with lipopolysaccharide (LPS). The primed cells were then treated with aqueous extract and saponin fraction of TT. The protein profile of the endothelial cells was assessed under normal and LPS-induced conditions using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 2D gel electrophoresis (2-DE). The levels of VCAM-1, ICAM-1, and E-selectin were estimated by use of western blotting. RESULTS: LPS-induced HUVECs and HBMECs were shown to significantly increase the expression of ICAM-1, VCAM-1, and E-selectin in comparison to control groups. Our findings revealed that TT extract resulted in significantly more reduced levels of proteome (80 spots) as well as all the three mentioned proteins compared with the effect of saponin fraction alone. CONCLUSION: TT extract and its saponin fraction exerted anti-inflammatory effects on HUVEC and HBMEC lines and reduced the expression of ICAM-1, VCAM-1, and E-selectin. However, the anti-inflammatory effect of aqueous extract was greater than that of saponin fraction. Therefore, TT could be considered as a potential candidate for the treatment or prevention of atherosclerosis.


Subject(s)
E-Selectin/drug effects , Endothelial Cells/drug effects , Intercellular Adhesion Molecule-1/drug effects , Plant Extracts/pharmacology , Saponins/pharmacology , Vascular Cell Adhesion Molecule-1/drug effects , Anti-Inflammatory Agents/pharmacology , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cells, Cultured , E-Selectin/biosynthesis , Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Proteome/drug effects , Tribulus , Vascular Cell Adhesion Molecule-1/biosynthesis
2.
J Drugs Dermatol ; 15(3): 319-23, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26954317

ABSTRACT

INTRODUCTION: Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat. METHODS: A PubMed search for the term "indigo naturalis" was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed. RESULTS: Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated. CONCLUSION: Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Nail Diseases/drug therapy , Phytotherapy/methods , Psoriasis/drug therapy , Administration, Topical , Cell Proliferation/drug effects , Cytokines/drug effects , Cytokines/metabolism , Drugs, Chinese Herbal/adverse effects , Drugs, Chinese Herbal/economics , Epidermis/drug effects , Humans , Indigofera , Indoles/adverse effects , Indoles/therapeutic use , Keratinocytes/drug effects , Oils/adverse effects , Oils/therapeutic use , Ointments/adverse effects , Ointments/therapeutic use , Phytotherapy/adverse effects , Phytotherapy/economics , Randomized Controlled Trials as Topic , Severity of Illness Index , Signal Transduction/drug effects , Skin/drug effects , Treatment Outcome , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/metabolism
3.
J Pharmacol Exp Ther ; 344(1): 41-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23033374

ABSTRACT

Raising high-density lipoprotein (HDL) levels is proposed as an attractive target to treat cardiovascular disease. However, a number of clinical studies examining the effect of HDL-raising therapies have been prematurely halted due to futility. Therefore there is a need for alternative therapies. Infusion of reconstituted HDL (rHDL) particles is still considered as a viable approach to increasing HDL levels. In this study we have profiled the anti-inflammatory effects of a trimeric-HDL particle. We show that trimeric apoA-I and rHDL particles promote cholesterol efflux to a similar rate as native apoA-I particles in both ABCA1-dependent and -independent pathways. Trimeric particles inhibited ICAM-1 and VCAM-1 expression and the ability of the endothelium to capture monocytes under shear flow. Monocyte activation, CD11b-dependent adhesion, and monocyte recruitment under shear flow conditions were perturbed by the trimeric particles. Our data suggest that trimeric rHDL particles can be constructed without any loss of function, preserving the anti-inflammatory effects of HDL that are key to its in vivo actions.


Subject(s)
Anti-Inflammatory Agents , Apolipoprotein A-I/chemistry , Apolipoprotein A-I/pharmacology , Lipoproteins, HDL/pharmacology , CD11b Antigen/biosynthesis , Cell Adhesion/drug effects , Cell Adhesion Molecules , Cell Separation , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Flow Cytometry , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Immunohistochemistry , Intercellular Adhesion Molecule-1/drug effects , Liposomes , Monocytes/metabolism , Particle Size , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology , Vascular Cell Adhesion Molecule-1/drug effects
4.
BJU Int ; 110(6 Pt B): E301-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22520557

ABSTRACT

UNLABELLED: What's known on the subject? and What does the study add? Pervasive inflammatory infiltrates, mainly composed of chronically activated T cells and monocytes/macrophages, have been observed in benign prostatic hyperplasia (BPH). Permixon®, a hexanic lipidosterolic extract of Serenoa repens (hexanic LSESr) used to treat urinary dysfunction in BPH patients, has anti-inflammatory activities. This paper provides new insights into the anti-inflammatory properties of Permixon®. We report that hexanic LSESr inhibits early steps of leukocyte infiltration in vitro by downregulating MCP-1/CCL2 and VCAM-1 expression. OBJECTIVE: To investigate the mechanisms by which hexanic lipidosterolic extract of Serenoa repens (hexanic LSESr) may prevent leukocyte infiltration in benign prostatic hyperplasia by studying its impact on monocyte chemoattractant protein 1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) and vascular cell adhesion molecule 1 (VCAM-1) expression in vitro. MATERIALS AND METHODS: After pretreatment with hexanic LSESr, human prostate (epithelial and myofibroblastic) cells and vascular endothelial cells were stimulated with proinflammatory cytokines. MCP-1/CCL2 and VCAM-1 mRNA expression was quantified by real-time PCR. ELISA kits were used to determine MCP-1/CCL2 levels in culture supernatants and VCAM-1 expression in living cells. RESULTS: Hexanic LSESr reduced MCP-1/CCL2 mRNA levels in both epithelial (BPH-1) and myofibroblastic (WPMY-1) prostate cell lines. Hexanic LSESr downregulated MCP1/CCL2 secretion by WPMY-1 cells in a concentration-dependent manner, more efficiently than Serenoa repens extracts obtained by supercritical carbon dioxide extraction. Hexanic LSESr inhibited tumour-necrosis-factor-α-induced MCP-1/CCL2 secretion by the human vascular endothelial cell line EAhy.926, as well as surface VCAM-1 protein expression, in a concentration-dependent manner. CONCLUSIONS: Hexanic LSESr impedes key steps of monocyte and T cell attraction and adherence by inhibiting MCP-1/CCL2 and VCAM-1 expression by human prostate and vascular cells in an inflammatory environment. These findings provide new insights into the anti-inflammatory effects of the hexanic lipidosterolic extract of Serenoa repens, Permixon®, in benign prostatic hyperplasia.


Subject(s)
Chemokine CCL2/antagonists & inhibitors , Chemokine CCL2/biosynthesis , Hexanes/pharmacology , Plant Extracts/pharmacology , Serenoa , Vascular Cell Adhesion Molecule-1/biosynthesis , Vascular Cell Adhesion Molecule-1/drug effects , Cells, Cultured , Humans
5.
Climacteric ; 15(2): 186-94, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22066752

ABSTRACT

BACKGROUND: The risks of hormone replacement therapy have led to a search for new alternatives such as phytoestrogens, plant compounds with estrogen-like biological activity. Isoflavones are the phytoestrogens most extensively studied and can be found in soybean, red clover and other plants. Due to this estrogen-like activity, phytoestrogens can have some effect on atherosclerosis. Human umbilical vein endothelial cells (HUVEC) have been extensively used to study the biology and pathobiology of human endothelial cells and most of the knowledge acquired is due to experiments with cultures of these cells. OBJECTIVE: To evaluate the effects of the phytoestrogen extracts from Glycine max soy bean, genistein, formononetin, biochanin A and daidzein, as well as a mixture of these extracts (Mix), on expression of adhesion molecules, VCAM-1, ICAM-1 and E-selectin, by endothelial cell HUVEC, stimulated with lipopolysaccharide. METHODS: HUVEC were cultured in medium EBM(2), pretreated with isoflavones for 24 and 48 h and then stimulated with lipopolysaccharide; in addition, isoflavones were added, after stimulation by lipopolysaccharide, to HUVEC. We evaluated the production of VCAM-1, ICAM-1 and E-selectin on cell surface, by cell-based enzyme immunoassay, and of sVCAM-1, sICAM-1 and sE-selectin in culture supernatant, by ELISA. RESULTS: Genistein, formononetin, biochanin A and daidzein, as well as the Mix were able to reduce VCAM-1, ICAM-1 and E-selectin on cell surface and in culture supernatant. Conclusion Isoflavones extracted from Glycine max soy bean, in vitro, presented antiatherogenic effects, reducing the expression of adhesion molecules and acting as preventive agents as well as therapeutic agents.


Subject(s)
E-Selectin/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Intercellular Adhesion Molecule-1/drug effects , Phytoestrogens/pharmacology , Vascular Cell Adhesion Molecule-1/drug effects , Cells, Cultured , Drug Therapy, Combination , E-Selectin/metabolism , Genistein/pharmacology , Humans , Intercellular Adhesion Molecule-1/metabolism , Isoflavones/pharmacology , Glycine max , Time Factors , Vascular Cell Adhesion Molecule-1/metabolism
6.
Nutr J ; 10: 122, 2011 Nov 07.
Article in English | MEDLINE | ID: mdl-22059644

ABSTRACT

BACKGROUND: Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. METHODS: Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-κB (NF-κB)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). RESULTS: O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. CONCLUSIONS: While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-κB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation.


Subject(s)
Dietary Fats/administration & dosage , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Inflammation/physiopathology , Obesity/physiopathology , Overweight/physiopathology , Adult , Biomarkers/blood , Blood Glucose/analysis , Cross-Over Studies , Dairy Products , Dinoprost/analogs & derivatives , Dinoprost/blood , Female , Humans , Inflammation/diet therapy , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/drug effects , Male , Middle Aged , NF-kappa B/drug effects , NF-kappa B/metabolism , Obesity/diet therapy , Overweight/diet therapy , Oxidative Stress/drug effects , Postprandial Period/drug effects , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/drug effects , Young Adult
7.
Can J Physiol Pharmacol ; 89(11): 811-8, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22029500

ABSTRACT

Resveratrol, a polyphenol compound with anti-inflammatory properties, has been previously evaluated for its beneficial effects in several ulcerative colitis models. However, the current study elucidates the effect of resveratrol on adhesion molecules, as well as its antioxidant efficacy in a trinitrobenzene sulfonic acid (TNBS)-induced ulcerative-colitis model. Colitis was induced by rectal instillation of TNBS, followed by daily per os administration of either sulphasalazine (300 mg/kg) or resveratrol (2 and 10 mg/kg) for 7 days. Administration of resveratrol decreased the ulcerative area and colon mass index; these effects were further supported by the reduction in colon inflammation grades, as well as histolopathological changes, and reflected by the stalling of body mass loss. The anti-inflammatory effects of resveratrol were indicated by lowered myeloperoxidase activity, and by suppressing ICAM-1 and VCAM-1 levels in the colon and serum. In addition, it restored a reduced colonic nitric oxide level and reinstated its redox balance, as evidenced by the suppression of lipid peroxides and prevention of glutathione depletion. The anti-ulcerative effect of the higher dose of resveratrol was comparable with those of sulphasalazine. The study confirms the anti-ulcerative effect of resveratrol in TNBS-induced experimental colitis via reduction of neutrophil infiltration, inhibition of adhesive molecules, and restoration of the nitric oxide level, as well as the redox status.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Adhesion Molecules/antagonists & inhibitors , Colitis, Ulcerative/drug therapy , Colon/drug effects , Inflammation/pathology , Stilbenes/pharmacology , Sulfasalazine/pharmacology , Animals , Body Weight/drug effects , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Colon/pathology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Glutathione/analysis , Glutathione/drug effects , Inflammation/chemically induced , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/drug effects , Intercellular Adhesion Molecule-1/physiology , Lipid Peroxidation/drug effects , Male , Peroxidase/analysis , Peroxidase/drug effects , Rats , Rats, Wistar , Resveratrol , Trinitrobenzenesulfonic Acid/toxicity , Vascular Cell Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/physiology
8.
Planta Med ; 77(16): 1782-7, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21614753

ABSTRACT

Development of early stage atherosclerosis involves the activation of endothelial cells by oxidized low-density lipoprotein (oxLDL) with subsequent increases in endothelial permeability and expression of adhesion molecules favoring the adherence of monocytes to the endothelium. Cryptotanshinone (CTS), a major compound derived from the Chinese herb Salvia miltiorrhiza, is known for its protective effects against cardiovascular diseases. The aim of this study was to determine whether CTS could prevent the oxLDL-induced early atherosclerotic events. OxLDL (100 µg/mL) was used to increase endothelial permeability and induce monocyte-endothelial cell adhesion in human umbilical vein endothelial cells (HUVECs). Endothelial nitric oxide (NO) concentrations, a permeability-regulating molecule, and expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured. Results show that a) endothelial hyperpermeability was suppressed by 94 % (p < 0.005), b) monocyte adhesion by 105 % (p < 0.01), and c) ICAM-1 and VCAM-1 expressions by 90 % (p < 0.01) and 150 % (p < 0.005), respectively, when CTS was applied. In contrast, CTS increased NO levels by 129 % (p < 0.01) and was found to be noncytotoxic in the concentrations between 1-10 µM. These findings indicate that CTS suppresses an increase in endothelial permeability, likely due to the restoration of NO bioavailability in endothelial cells. They also indicate that CTS may attenuate monocyte adhesion to endothelial cells through the inhibition of adhesion molecules' expression. Thus, CTS may play an important role in the prevention of early or pre-lesional stage of atherosclerosis.


Subject(s)
Atherosclerosis/prevention & control , Drugs, Chinese Herbal/pharmacology , Phenanthrenes/pharmacology , Salvia miltiorrhiza/chemistry , Atherosclerosis/chemically induced , Biological Availability , Cell Adhesion/drug effects , Cell Survival , Cells, Cultured , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/physiology , Humans , Intercellular Adhesion Molecule-1/drug effects , Intercellular Adhesion Molecule-1/metabolism , Lipoproteins, LDL/toxicity , Monocytes/drug effects , Monocytes/physiology , Nitric Oxide/pharmacokinetics , Permeability/drug effects , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/metabolism
9.
Molecules ; 15(9): 6423-35, 2010 Sep 14.
Article in English | MEDLINE | ID: mdl-20877233

ABSTRACT

The use of indigo naturalis to treat psoriasis has proved effective in our previous clinical studies. The present study was designed to examine the anti-inflammatory effect of indigo naturalis in primary cultured human umbilical vein endothelial cells (HUVECs). Pretreatment of cells with indigo naturalis extract attenuated TNF-α-induced increase in Jurkat T cell adhesion to HUVECs as well as decreased the protein and messenger (m)RNA expression levels of vascular cell adhesion molecule-1 (VCAM-1) on HUVECs. Indigo naturalis extract also inhibited the protein expression of activator protein-1 (AP-1)/c-Jun, a critical transcription factor for the activation of VCAM-1 gene expression. Since the reduction of lymphocyte adhesion to vascular cells by indigo naturalis extract could subsequently reduce the inflammatory reactions caused by lymphocyte infiltration in the epidermal layer and help to improve psoriasis, this study provides a potential mechanism for the anti-inflammatory therapeutic effect of indigo naturalis extract in psoriasis.


Subject(s)
Endothelial Cells/drug effects , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Tumor Necrosis Factor-alpha/physiology , Umbilical Veins/cytology , Vascular Cell Adhesion Molecule-1/analysis , Cell Adhesion/drug effects , Humans , Inflammation/drug therapy , Jurkat Cells/drug effects , Jurkat Cells/physiology , Psoriasis/drug therapy , RNA, Messenger/analysis , RNA, Messenger/drug effects , Transcription Factor AP-1/antagonists & inhibitors , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/genetics
10.
J Nat Prod ; 73(7): 1318-22, 2010 Jul 23.
Article in English | MEDLINE | ID: mdl-20557071

ABSTRACT

A super-carbon-chain compound, symbiopolyol (1a), was isolated from a symbiotic dinoflagellate of the jellyfish Mastigias papua. Although a direct comparison between symbiopolyol (1a) and lingshuiol B has not been completed, symbiopolyol (1a) is suggested to be the enantiomer of lingshuiol B. The structure of 1a, including its partial relative configuration, was elucidated on the basis of interpretation of spectroscopic data and chemical transformations. This compound exhibited significant inhibitory activity against the expression of VCAM-1 in human umbilical vein endothelial cells (HUVEC).


Subject(s)
Alkenes/isolation & purification , Alkenes/pharmacology , Dinoflagellida/chemistry , Pyrans/isolation & purification , Pyrans/pharmacology , Scyphozoa/microbiology , Vascular Cell Adhesion Molecule-1/drug effects , Alkenes/chemistry , Animals , Humans , Inhibitory Concentration 50 , Molecular Structure , Pyrans/chemistry , Vascular Cell Adhesion Molecule-1/metabolism
11.
J Nutr Sci Vitaminol (Tokyo) ; 56(2): 87-97, 2010.
Article in English | MEDLINE | ID: mdl-20495289

ABSTRACT

Diabetic encephalopathy is a severe complication in patients with long-term hyperglycemia. Oxidative stress is thought to be closely implicated in this disorder, so in this study, we examined whether grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant derived from grape seeds, could reduce the injuries in the cerebral cortex of diabetic rats by modulating advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-kappaB p65) pathway, which is crucial in oxidative stress. Body weight and serum AGEs were tested; cerebral cortexes were isolated for morphological observations and the pyramidal cell layers were immunohistochemically stained for the detection of RAGE, NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well. For RAGE and NF-kappaB p65, quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) was employed for determination of mRNA levels, and western blot was used to detect protein expression. Our results showed that long term hyperglycemia in diabetic rats caused the degeneration of neurons and the up-regulation of serum AGEs, and also the up-regulation of RAGE, NF-kappaB p65, VCAM-1 and ICAM-1 in the brain. We found that GSPE treatment improved the pathological changes of diabetic rats by modulating the AGEs/RAGE/NF-kappaB p65 pathway. This study enables us to further understand the key role that the AGEs/RAGE/NF-kappaB pathway plays in the pathogenesis of diabetic encephalopathy, and confirms that GSPE might be a therapeutical means to the prevention and treatment of this disorder.


Subject(s)
Brain Diseases, Metabolic/drug therapy , Cerebral Cortex/drug effects , Diabetes Complications/drug therapy , Diabetes Mellitus, Experimental/metabolism , Glycation End Products, Advanced/metabolism , Grape Seed Extract/therapeutic use , NF-kappa B/metabolism , Proanthocyanidins/therapeutic use , Animals , Antioxidants/therapeutic use , Blotting, Western/methods , Body Weight/drug effects , Brain Diseases, Metabolic/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Disease Models, Animal , Glycation End Products, Advanced/blood , Intercellular Adhesion Molecule-1/drug effects , Intercellular Adhesion Molecule-1/metabolism , Male , NF-kappa B/drug effects , Oxidative Stress/drug effects , Rats , Rats, Wistar , Receptor for Advanced Glycation End Products , Receptors, Immunologic/drug effects , Receptors, Immunologic/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Streptozocin , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/metabolism
12.
J Ethnopharmacol ; 123(2): 250-6, 2009 Jun 22.
Article in English | MEDLINE | ID: mdl-19429369

ABSTRACT

The flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae) are used in traditional medicine to treat asthma, chronic bronchitis, and acute pleurisy in China and Korea. However, the pharmacological actions of Inula britannica L. var. chinensis on endothelial cells and inflammatory monocytes are not clear. In this study, we investigated whether bigelovin, a sesquiterpene lactone isolated from the flowers of Inula britannica L. var. chinensis, inhibits monocyte adhesion and adhesion molecule expression in brain endothelial cells. We measured tumor necrosis factor-alpha (TNF-alpha)-enhanced Raw264.7 monocyte binding to brain endothelial cells and the levels of cell adhesion molecules, including vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and endothelial-selectin (E-selectin) on the surface of brain endothelial cells. Bigelovin significantly inhibited these in a dose-dependent manner without affecting cell viability. Furthermore, bigelovin suppressed the nuclear factor kappaB (NF-kappaB) promoter-driven luciferase activity, NF-kappaB activation, and degradation of NF-kappaB inhibitor protein alpha (IkappaBalpha). These results indicate that bigelovin inhibits inflammatory monocyte adhesion to endothelial cells and the expression of VCAM-1, ICAM-1, and E-selectin by blocking IkappaBalpha degradation and NF-kappaB activation.


Subject(s)
Down-Regulation/drug effects , Inula/chemistry , Lactones/pharmacology , NF-kappa B/metabolism , Sesquiterpenes/pharmacology , Animals , Brain/cytology , Brain/drug effects , Cell Adhesion/drug effects , Cell Line , Dose-Response Relationship, Drug , E-Selectin/drug effects , E-Selectin/metabolism , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Flowers , Gene Expression Regulation/drug effects , I-kappa B Proteins/drug effects , I-kappa B Proteins/metabolism , Intercellular Adhesion Molecule-1/drug effects , Intercellular Adhesion Molecule-1/metabolism , Lactones/administration & dosage , Lactones/isolation & purification , Medicine, East Asian Traditional , Mice , Monocytes/drug effects , Monocytes/metabolism , NF-KappaB Inhibitor alpha , NF-kappa B/drug effects , Sesquiterpenes/administration & dosage , Sesquiterpenes/isolation & purification , Tumor Necrosis Factor-alpha/administration & dosage , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/metabolism
13.
Menopause ; 15(3): 542-50, 2008.
Article in English | MEDLINE | ID: mdl-18467954

ABSTRACT

OBJECTIVE: In the search for safer approaches to address menopausal symptoms, the administration of plant-derived estrogens has gained popularity. Recent evidence suggests that these compounds may act neutrally or even beneficially on surrogate cardiovascular risk markers in postmenopausal women. However, little is known of the effects of phytoestrogens on vascular cells. DESIGN: Endothelial expression of leukocyte adhesion molecules plays a critical role in the development of atherosclerosis and in plaque destabilization, and estrogen reduces the expression of these proatherogenic molecules. We studied the regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells by phytoestrogens contained in red clover extracts. Moreover, we characterized the mechanistic basis for these actions. RESULTS: Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide. The addition of red clover extracts to reproductive life or menopausal concentrations of 17beta-estradiol results in an additive decrease in expression of endothelial adhesion molecules. The reduction of ICAM-1 and VCAM-1 expression in the presence of red clover extracts is paralleled by a cytoplasmic stabilization of the proinflammatory transcription factor nuclear factor-kappaB. CONCLUSIONS: Red clover extracts act as anti-inflammatory and antiatherogenic agents on human endothelial cells by reducing the expression of the leukocyte adhesion molecules ICAM-1 and VCAM-1. On the basis of these results, red clover extracts may induce beneficial actions on human vessels.


Subject(s)
Endothelial Cells/drug effects , Isoflavones/pharmacology , Phytoestrogens/pharmacology , Plant Extracts/pharmacology , Trifolium , Cells, Cultured , Humans , Intercellular Adhesion Molecule-1/drug effects , Isoflavones/chemistry , NF-kappa B/drug effects , Umbilical Veins/cytology , Vascular Cell Adhesion Molecule-1/drug effects
15.
J Cardiovasc Pharmacol ; 49(5): 293-8, 2007 May.
Article in English | MEDLINE | ID: mdl-17513948

ABSTRACT

Although evidence has shown that grape seed proanthocyanidin extracts (GSPE) can selectively inhibit cell adhesion molecule expression induced by advanced glycation end products (AGEs), the underlying molecular mechanism has not been extensively characterized. To study the antiinflammation mechanism of GSPE, we investigated the effect of GSPE on Von Willebrand factor (vWF) content and the expression of vascular cell adhesion molecule-1 (VCAM-1) induced by AGEs and the effect of GSPE on peroxisome proliferators-activated receptor gamma (PPAR gamma) and receptor for AGEs (RAGE) expression in human umbilical vein endothelial cells (HUVEC). HUVEC were preincubated with or without GSPE of different concentrations (10 mg/L, 50 mg/L, and 100 mg/L) for 4 hours before being treated with 200 mg/L AGEs or unmodified bovine serum albumin (BSA) for 24 hours. The expression of RAGE and PPAR gamma was investigated by Western blot. VCAM-1 expression was measured by flow cytometry and vWF content by enzyme-linked immunosorbent assay (ELISA). Results showed that GSPE significantly inhibited the expression of VCAM-1 in HUVEC and reduced the content of vWF in culture fluid induced by AGEs in a dose-dependent manner. AGEs activated the expression of RAGE and inhibited PPAR gamma expression in HUVEC, whereas GSPE inhibited the expression of RAGE through activation of PPAR gamma in HUVEC simultaneously. These findings indicated that GSPE inhibited the cell inflammatory factor expression and protected the function of endothelial cell through activation of PPAR gamma expression and inhibition of RAGE expression.


Subject(s)
Glycation End Products, Advanced/pharmacology , PPAR gamma/biosynthesis , PPAR gamma/drug effects , Plant Extracts/pharmacology , Proanthocyanidins/pharmacology , Vascular Cell Adhesion Molecule-1/biosynthesis , Vascular Cell Adhesion Molecule-1/drug effects , Analysis of Variance , Blotting, Western , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Glycation End Products, Advanced/metabolism , Grape Seed Extract , Humans , Inflammation Mediators/metabolism , Serum Albumin, Bovine/pharmacology , Umbilical Veins/cytology , von Willebrand Factor/drug effects
16.
J Cardiovasc Pharmacol ; 49(1): 20-6, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17261959

ABSTRACT

Antiinflammatory properties of losartan are currently unclear. This study tested the hypothesis that losartan itself has an antiinflammatory effect comparable to that of simvastatin. Human umbilical vein endothelial cells (HUVECs) were (1) incubated with culture medium alone, (2) incubated with added C-reactive protein (CRP) (25, 50, 75, and 100 microg/mL) for stimulation, and (3) pretreated with losartan (stepwise increased dose: 100, 300, 500, and 750 micromol/L) and simvastatin (stepwise increased dose: 25, 50, 75, and 100 micromol/L) for 4 hours before adding CRP for stimulation. Surface expression of vascular cell adhesion molecule-1 (VCAM-1) was determined by flow cytometry. Supernatant levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) were measured by ELISA. Experimental results showed that the effect of CRP on VCAM-1 expression and supernatant levels of MCP-1 and IL-6 increases stepwise as CRP concentrations increase from 25 to 50 to 75 to 100 microg/mL (all P < 0.001). The effect of CRP on VCAM-1 expression in HUVECs and supernatant levels of MCP-1 and IL-6 were significantly suppressed by 25 micromol/L simvastatin with stepwise increased suppression as simvastatin dose increased to 50, 75, and 100 micromol/L (all P < 0.0001). However, losartan did not significantly suppress CRP's effect on VCAM-1 expression in HUVECs (P > 0.5). Moreover, losartan did not suppress CRP's effect on MCP-1 and IL-6 secretion unless a high dose (> or =500 micromol/L) of losartan was used. Compared with simvastatin, losartan had less effect on suppression of CRP-mediated inflammation.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anticholesteremic Agents/pharmacology , C-Reactive Protein/physiology , Endothelial Cells/drug effects , Losartan/pharmacology , Simvastatin/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cells, Cultured , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Humans , Receptor, Angiotensin, Type 1/biosynthesis , Receptor, Angiotensin, Type 1/genetics , Vascular Cell Adhesion Molecule-1/biosynthesis , Vascular Cell Adhesion Molecule-1/drug effects , Vascular Cell Adhesion Molecule-1/genetics
17.
Phytomedicine ; 13(4): 230-5, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16492524

ABSTRACT

Inflammation plays an important role in both the initiation of atherosclerosis and development of atherothrombotic events. The adherence of leukocytes/monocytes to the endothelium is an early event in atherogenesis. Phytotherapeutica as garlic and garlic extracts were shown to have beneficial modulating effects in patients with atherosclerotic disease. The aim of this study was to evaluate in vitro the influence of water-soluble garlic (Allium sativum) extract on the cytokine-induced expression of endothelial leukocyte adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106). Cytokine-induced expression of cellular adhesion molecules was measured on primary human coronary artery endothelial cell (HCAEC) cultures. HCAEC were cultured in microvascular endothelial cell growth medium and preincubated with garlic extract at various concentrations (0.25-4.0 mg/ml), after which human interleukin-1alpha (IL-1alpha, 10 ng/ml) was added for 1 day. Fluorescein isothiocyanate (FITC)-labeled anti-ICAM-1 and FITC-labeled anti-VCAM-1 were used to analyze the IL-1alpha-induced expression of ICAM-1 and VCAM-1 by flow cytometry. Incubation of HCAEC with garlic extract significantly decreased ICAM-1 and VCAM-1 expression induced by IL-1alpha. In addition, we examined the effects of garlic extract on the adhesion of monocytes to endothelial cells, using the monocytic U937 cell line. The presence of garlic extract significantly inhibited the adhesion of monocytes to IL-1alpha-stimulated endothelial cells. These results indicate that garlic extract modulates the expression of ICAM-1 and VCAM-1, thus potentially contributing to the beneficial effects traditionally attributed to garlic.


Subject(s)
Endothelial Cells/drug effects , Garlic/chemistry , Intercellular Adhesion Molecule-1/drug effects , Plant Extracts/pharmacology , Vascular Cell Adhesion Molecule-1/drug effects , Cell Adhesion/drug effects , Cells, Cultured , Coronary Vessels/cytology , Coronary Vessels/drug effects , Dose-Response Relationship, Drug , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Flow Cytometry/methods , Humans , Intercellular Adhesion Molecule-1/analysis , Intercellular Adhesion Molecule-1/biosynthesis , Interleukin-1/pharmacology , Monocytes/drug effects , Vascular Cell Adhesion Molecule-1/analysis , Vascular Cell Adhesion Molecule-1/biosynthesis
18.
Am J Clin Nutr ; 82(6): 1260-8; quiz 1365-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16332659

ABSTRACT

BACKGROUND: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. OBJECTIVE: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. DESIGN: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. RESULTS: Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes. CONCLUSION: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.


Subject(s)
C-Reactive Protein/analysis , Cardiovascular Diseases/blood , Estrogen Receptor beta/genetics , Isoflavones/pharmacology , Postmenopause , Soy Foods , Aged , Biomarkers/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Cross-Over Studies , Double-Blind Method , Equol , Estrogen Receptor beta/metabolism , Female , Food, Fortified , Genotype , Humans , Isoflavones/biosynthesis , Isoflavones/urine , Middle Aged , Phytoestrogens/metabolism , Phytoestrogens/urine , Polymorphism, Single Nucleotide , Risk Factors , Vascular Cell Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/drug effects
19.
Biochem Pharmacol ; 70(8): 1192-9, 2005 Oct 15.
Article in English | MEDLINE | ID: mdl-16154540

ABSTRACT

To elucidate the molecular mechanism by which antioxidants alleviate atherosclerosis, we investigated the effect of crocetin, a naturally occurred carotinoid with potent antioxidant power, on vascular cell adhesion molecule-1 (VCAM-1) expression in atherosclerotic rabbits. Twenty-four male New Zealand White rabbits were allocated to three groups fed on standard diet (control group), high lipid diet (HLD group) or high lipid diet supplemented with crocetin (crocetin group), respectively. After 8 weeks of treatment, rabbits in HLD group developed severe hypercholesterolemia and atherosclerosis in aortas, together with a significantly up-regulated expression of both protein and mRNA for VCAM-1. In contrast, supplementation with crocetin resulted in markedly ameliorated atherosclerosis, coupled with a significantly decreased VCAM-1 expression, though plasma lipids level remained comparable to that of HLD group. Regression analysis revealed a positive correlation between VCAM-1 expression and the extent of atherosclerosis (P < 0.01). In addition, immunohistochemical analysis showed an increased activation of nuclear factor kappa B (NF-kappaB), a redox sensitive transcription factor essential for VCAM-1 expression, in aortas from rabbits fed on high lipid diet, which was evidently suppressed by crocetin supplementation. These findings suggest that the antiatherosclerotic effect of crocetin might be attributed, at least in part, to the suppressed expression of VCAM-1, which might result from reduced NF-kappaB activation. This study provides a further insight into the molecular mechanism by which antioxidants attenuate atherosclerosis and suggests a potential target for the treatment of atherosclerosis with antioxidants.


Subject(s)
Atherosclerosis/metabolism , Carotenoids/pharmacology , Hypercholesterolemia/metabolism , Vascular Cell Adhesion Molecule-1/drug effects , Animals , Atherosclerosis/complications , Base Sequence , DNA Primers , Hypercholesterolemia/complications , Immunohistochemistry , Male , RNA, Messenger/genetics , Rabbits , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism , Vitamin A/analogs & derivatives
20.
Nutr Metab Cardiovasc Dis ; 14(4): 180-5, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15553594

ABSTRACT

BACKGROUND AND AIM: Long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against atherosclerotic disease, and serum levels of soluble cellular adhesion molecules (sCAMs) possibly reflect the inflammatory process underlying atherosclerosis. We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), and the correlation between sCAMs and the fatty acid composition of granulocyte membranes. METHODS AND RESULTS: Sixty healthy volunteers were randomly assigned to receive a daily supplement of n-3 PUFA 6.6 g, n-3 PUFA 2.0 g, or olive oil for 12 weeks in a double blind design. A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry. After supplementation with 6.6 g of n-3 PUFA, there was a significant decrease only in sP-selectin, which a gender subanalysis showed to be more marked in men. Among the women, there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group. CONCLUSIONS: The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects, thus suggesting a decrease in platelet reactivity or endothelial activation. However, the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose.


Subject(s)
Arteriosclerosis/prevention & control , Fatty Acids, Omega-3/administration & dosage , Intercellular Adhesion Molecule-1/blood , P-Selectin/blood , Vascular Cell Adhesion Molecule-1/blood , Adult , Biomarkers/blood , Dietary Supplements , Docosahexaenoic Acids/blood , Dose-Response Relationship, Drug , Double-Blind Method , Female , Granulocytes/metabolism , Humans , Intercellular Adhesion Molecule-1/drug effects , Male , P-Selectin/drug effects , Sex Factors , Vascular Cell Adhesion Molecule-1/drug effects
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