scholarly journals Anti-Atherogenic Effects of Orlistat on Obesity-Induced Vascular Oxidative Stress Rat Model

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 251
Author(s):  
Zaidatul Akmal Othman ◽  
Zaida Zakaria ◽  
Joseph Bagi Suleiman ◽  
Wan Syaheedah Wan Ghazali ◽  
Mahaneem Mohamed
Keyword(s):  
Oxidative Stress ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Inflammatory Marker ◽  
Density Lipoprotein ◽  
Normal Group ◽  
Anti Inflammatory ◽  
Cell Adhesion Molecule 1 ◽  
Vascular Oxidative Stress

Obesity is typically linked to oxidative stress and inflammation, which lead to vascular damage and initiate the progression of atherosclerosis. The aim of this study was to determine the anti-atherosclerotic effect of orlistat on obesity-induced vascular oxidative stress in obese male rats. Twenty-four male Sprague–Dawley rats were categorized into two groups: normal (Normal group, n = 6) and high-fat diet (HFD group, n = 12). After six weeks, obese rats in the HFD group were administered either with distilled water (OB group) or orlistat 10 mg/kg/day (OB/OR group) for another six weeks. The OB group had a significant increase in lipid profiles (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)) and decrease in high-density lipoprotein (HDL) level compared to the Normal group. The aortic antioxidants enzymes activities (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and catalase (CAT)) as well as total glutathione (GSH) and total antioxidant capacity (TAC) of the OB group were significantly decreased compared to the Normal group. Furthermore, pro-inflammatory atherosclerotic markers (tumour necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1)) expressions were increased significantly, and anti-inflammatory marker (interleukin-10 (IL-10)) was decreased significantly in the OB group compared to the Normal group. Treatment with orlistat significantly improved lipid profile, increased antioxidant enzymes and expression of anti-inflammatory markers, and decreased the expression of the pro-inflammatory marker compared to the OB group. These findings may suggest the therapeutic effect of orlistat in attenuating the progression of the atherosclerotic stage in obesity.

Chalcone Derivatives: Anti-inflammatory Potential and Molecular Targets Perspectives

2017 ◽  
Vol 17 (28) ◽  
pp. 3146-3169 ◽  
Author(s):  
Debarshi Kar Mahapatra ◽  
Sanjay Kumar Bharti ◽  
Vivek Asati
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Molecular Targets ◽  
Inflammatory Activity ◽  
Leukotriene D4 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Chalcone Derivatives ◽  
Anti Inflammatory ◽  
Cell Adhesion Molecule 1

Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold has gained considerable scientific interest in medicinal chemistry owing to its simple chemistry, ease in synthesizing a variety of derivatives and exhibiting a broad range of promising pharmacological activities by modulating several molecular targets. A number of natural and (semi-) synthetic chalcone derivatives have demonstrated admirable anti-inflammatory activity due to their inhibitory potential against various therapeutic targets like Cyclooxygenase (COX), Lipooxygenase (LOX), Interleukins (IL), Prostaglandins (PGs), Nitric Oxide Synthase (NOS), Leukotriene D4 (LTD4), Nuclear Factor-κB (NF- κB), Intracellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Monocyte Chemoattractant Protein-1 (MCP-1) and TLR4/MD-2, etc. The chalcone scaffold with hydroxyl, methoxyl, carboxyl, prenyl group and/or heterocyclic ring substitution like thiophene/furan/indole showed promising anti-inflammatory activity. In this review, a comprehensive study (from the year 1991 to 2016) on multi-targets of inflammatory interest, related inflammation reactions and their treatment by chalcone-based inhibitors acting on various molecular targets entailed in inflammation, Structure-Activity Relationships (SARs), Mechanism of Actions (MOAs), and patents are highlighted.

Statins reduce oxidized low-density lipoprotein levels, but do not alter soluble intercellular cell-adhesion molecule-1 and vascular cell-adhesion molecule-1 levels in subjects with hypercholesterolaemia

2004 ◽  
Vol 106 (2) ◽  
pp. 215-217 ◽  
Author(s):  
Robert S. ROSENSON ◽  
David WOLFF ◽  
Christine C. TANGNEY
Keyword(s):  
Cell Adhesion ◽  
Statin Therapy ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vascular Cell Adhesion ◽  
Lag Times ◽  
Cell Adhesion Molecule 1 ◽  
Intercellular Cell Adhesion Molecule

ICAM-1 (intercellular cell-adhesion molecule-1) and VCAM-1 (vascular cell-adhesion molecule-1) are cell-adhesion molecules that have an essential role in monocyte recruitment. In the present study we have investigated (i) whether statins reduce soluble levels of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1), and the relationship between resistance of LDL (low-density lipoprotein) to in vitro oxidation and sICAM-1 and sVCAM-1 levels. Whole blood samples were obtained from 55 healthy non-smoking adults (aged 35–65 years) with moderate (LDL-cholesterol, 3.4–4.9 mmol/l) hypercholesterolaemia participating in a randomized double-blinded, 8-week trial comparing pravastatin (40 mg), simvastatin (20 and 80 mg) and placebo. sICAM-1 levels (means±S.D.) increased slightly from 12.2±4.2 to 13.6±4.2 ng/ml with statin therapy, whereas, among placebo-assigned subjects, levels were unchanged (11.8±5.0 and 11.8±3.9 ng/ml). sVCAM-1 increased from 18.9±10.1 to 21.1±7.4 ng/ml among those on active therapy and slightly declined with placebo assignment (19.8±8.8 to 19.4±6.4 ng/ml). Lag times increased with statin therapy from 74.3±39.8 min to 98.3±57.8 min (P=0.003), and were unchanged in the placebo group (from 103.1±61.1 to 90.8±65.9 min; P=0.48). There were no significant changes between statin and placebo therapy for sICAM-1, sVCAM-1 or lag times (P=0.09, 0.16 and 0.067 respectively). Changes in sICAM-1 and sVCAM-1 were not correlated with the change in lag times. In contrast with the known effects of oxidized LDL on gene activation of ICAM-1 and VCAM-1, lag times did not correlate with sICAM-1 and sVCAM-1. Statin therapy improved lag times, but has no effect on sICAM-1 or sVCAM-1 levels.

Magnolol Reduced TNF-α-Induced Vascular Cell Adhesion Molecule-1 Expression in Endothelial Cells via JNK/p38 and NF-κB Signaling Pathways

2014 ◽  
Vol 42 (03) ◽  
pp. 619-637 ◽  
Author(s):  
Chan-Jung Liang ◽  
Chiang-Wen Lee ◽  
Hsin-Ching Sung ◽  
Yung-Hsiang Chen ◽  
Shu-Huei Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Cell Adhesion Molecule 1

Expression of cell adhesion molecules by the endothelium and the attachment of leukocytes to these cells play major roles in inflammation and cardiovascular disorders. Magnolol, a major active component of Magnolia officinalis, has antioxidative and anti-inflammatory properties. In the present study, the effects of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells (HAECs) and the related mechanisms were investigated. TNF-α induced VCAM-1 protein expression and mRNA stability were significantly decreased in HAECs pre-treated with magnolol. Magnolol significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-α-treated HAECs. The decrease in VCAM-1 expression in response to TNF-α treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor. Magnolol also attenuates NF-κB activation and the translocation of HuR (an RNA binding protein) in TNF-α-stimulated HAECs. The VCAM-1 expression was weaker in the aortas of TNF-α-treated apo-E deficient mice with magnolol treatment. These data demonstrate that magnolol inhibits TNF-α-induced JNK/p38 phosphorylation, HuR translocation, NF-κB activation, and thereby suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken together, these results suggest that magnolol has an anti-inflammatory property and may play an important role in the prevention of atherosclerosis and inflammatory responses.

scholarly journals ChaiQi Decoction Alleviates Vascular Endothelial Injury by Downregulating the Inflammatory Response in ApoE-Model Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Bingran Wang ◽  
Jiayan Zhang ◽  
Yuhong Lu ◽  
Long Peng ◽  
Wenling Yuan ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Inflammatory Response ◽  
Adhesion Molecule ◽  
Abdominal Aorta ◽  
Cell Adhesion Molecule ◽  
Density Lipoprotein ◽  
Endothelial Injury ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
Cell Adhesion Molecule 1

Metabolic syndrome (MetS) is a pathological state of metabolic disorders that primarily occur in human proteins, fats, and carbohydrates. It is a complex cluster of core metabolic disorder syndromes including obesity, hyperglycemia, dyslipidemia, and hypertension, and vascular endothelial injury, occurring over time. The currently available treatment options cannot effectively manage MetS. In our previous research, we revealed ChaiQi decoction (CQD) as an effective prescription for improving MetS; however, the specific mechanism remains unclear. Herein, we assessed the efficacy and mechanism of CQD in ApoE gene knockout (ApoE-) mice. Mice were administered with CQD daily for 12 weeks, and the measurement of their body weight was taken monthly. To evaluate the metabolic levels of mice, we determined the fasting blood glucose (FBG), fasting serum insulin (FINS), insulin resistance index (IRI), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Furthermore, immunohistochemical analysis was adopted to determine the expression of ICAM-1 and VCAM-1 in vascular endothelium, while an optical microscope was adopted to observe the pathological morphology of abdominal aorta in mice. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were determined using the ELISA method, whereas Western blotting was used to determine nuclear factor- (NF-) κB p65. Of note, intragastric CQD administration ameliorated ApoE-model mice, as evidenced by reduced levels of FBG, FINS, IRI, TG, TC, and LDL-C. Furthermore, CQD alleviated vascular endothelial injury and regularized the structure of the abdominal aorta by downregulating the expressions of proinflammatory cytokines TNF-α, IL-6, ICAM-1, VCAM-1, and NF-κB p65. Overall, these findings advocated that CQD ameliorates metabolic levels and vascular endothelial injury in mice by downregulating the inflammatory response and thus may be utilized as a novel MetS therapy.

scholarly journals The Presence of Cholesteryl Ester Transfer Protein (CETP) in Endothelial Cells Generates Vascular Oxidative Stress and Endothelial Dysfunction

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 69
Author(s):  
Amarylis C. B. A. Wanschel ◽  
Daniele M. Guizoni ◽  
Estela Lorza-Gil ◽  
Alessandro G. Salerno ◽  
Adriene A. Paiva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Dysfunction ◽  
Transgenic Mice ◽  
Cholesteryl Ester Transfer Protein ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Transfer Protein ◽  
Cell Adhesion Molecule 1

Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Cholesterol levels and oxidative stress are key contributors to endothelial damage, whereas high levels of plasma high-density lipoproteins (HDL) could prevent it. Cholesteryl ester transfer protein (CETP) is one of the most potent endogenous negative regulators of HDL-cholesterol. However, whether and to what degree CETP expression impacts endothelial function, and the molecular mechanisms underlying the vascular effects of CETP on endothelial cells, have not been addressed. Acetylcholine-induced endothelium-dependent relaxation of aortic rings was impaired in human CETP-expressing transgenic mice, compared to their non-transgenic littermates. However, endothelial nitric oxide synthase (eNOS) activation was enhanced. The generation of superoxide and hydrogen peroxide was increased in aortas from CETP transgenic mice, while silencing CETP in cultured human aortic endothelial cells effectively decreased oxidative stress promoted by all major sources of ROS: mitochondria and NOX2. The endoplasmic reticulum stress markers, known as GADD153, PERK, and ARF6, and unfolded protein response effectors, were also diminished. Silencing CETP reduced endothelial tumor necrosis factor (TNF) α levels, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression, diminishing monocyte adhesion. These results support the notion that CETP expression negatively impacts endothelial cell function, revealing a new mechanism that might contribute to atherosclerosis.

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