scholarly journals Comparative Analysis of Luteolin and Luteolin-7-O-Glucoside on anti-Atherogenesis in ApoE Knockout Mice with Hyperhomocysteinemia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yeon-A. Son ◽  
Chung-Mu Park ◽  
Youngsun Song

AbstractLuteolin is a naturally occurring flavone that reportedly has anti-inflammatory effect. Flavones in plants are usually present in the form of glucosides, although occasionally they are found as aglycones. The bioavailability of flavones may differ when consumed as either aglycones or glucosides. Nonetheless, numerous studies focused on the biological activity of flavonoid aglycones or that in vitro. These findings are supporting reason to compare the anti-atherogenic effect of aglycone and glucoside forms of flavones in vivo. Male ApoE knockout mice (n = 28, 6-week-old) were divided randomly into 4 groups of 7 mice: negative control group, homocysteine control group, luteolin and luteolin7-O-glucoside groups with homocysteine. All animals were fed by a high-fat diet, modified by AIN-93, containing 0.5% of cholesterol and 45% of fat. Luteolin and luteolin-7-O-glycoside were given daily by gavage for 5 weeks (50 mg/kg BW, respectively). To induce hyperhomocysteinemia, homocysteine was provided as a drinking water (0.9g/L). Administration of homocysteine did not affect body weight gain, feed intake and feed efficiency ratio among groups. Homocysteine feeding sharply increased serum concentrations of homocysteine and triglyceride as well as adhesion molecules including monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, which were attenuated by the administration of luteolin and luteolin-7-O-glucoside (p < 0.05). Homocysteine administration produced development of atherosclerotic process by the induction of hepatic inducible nitric oxide synthase and cyclooxygenase-2 as well as aortic intercellular adhesion molecule expressions along with diminished expressions of antioxidative enzymes, such as hepatic glutathione reductase (GR), aortic GR and glutathione peroxidase (p < 0.05). Administration of both flavones down-regulated expressions of inflammatory mediators and adhesion molecules as well as up-regulated expressions of antioxidative enzymes (p < 0.05). These data were in accordance with the histopathological observations which were analyzed by hematoxylin and eosin (H&E) stain and immunohistochemistry. In a comparison of both agents, luteolin more potently attenuated inflammation and oxidative stress than luteolin-7-O-glucoside. These results exhibit that luteolin and luteolin-7-O-glycoside ameliorated atherogenic processes through the regulation of inflammation and oxidative stress in ApoE knockout mice with hyperhomocysteinemia. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government of MOE (No 201704340001).

Author(s):  
Karynne Grutter Lopes ◽  
Paulo Farinatti ◽  
Daniel Alexandre Bottino ◽  
Maria das Graças Coelho de Souza ◽  
Priscila Alves Maranhão ◽  
...  

BACKGROUND: Age-related mechanisms of sarcopenia associated with vascular function have been recently suggested. This study compared and tested associations between muscle mass and strength, microcirculation, inflammatory biomarkers, and oxidative stress in older adults classified as sarcopenic and non-sarcopenic. METHODS: Thirty-three physically inactive individuals (72±7 yrs) were assigned to age-matched sarcopenic (SG) and non-sarcopenic (NSG) groups. Between-group comparisons were performed for appendicular skeletal mass (ASM), handgrip and isokinetic strength, microvascular function and morphology, C-reactive protein, insulin-like growth factor-1, tumor necrosis factor-alpha, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, endothelin-1, and oxidized low-density lipoprotein. RESULTS: ASM and knee isokinetic strength were lower in SG than NSG (P <  0.05). No difference between groups was found for outcomes of microvascular function and morphology, but log-transformed IL-6 concentration was twice greater in SG vs. NSG (P = 0.02). Correlations between ASM index, handgrip and knee isokinetic strength vs. markers of microcirculatory function, capillary diameters, vascular reactivity, and endothelial injury were found only in SG. CONCLUSION: Decreased ASM index and strength have been associated with microcirculatory profile, indicating that microcirculation impairment may be involved somehow in Sarcopenia development. The inflammation status, particularly elevated IL-6, seems to play an important role in this process.


1998 ◽  
Vol 18 (12) ◽  
pp. 1336-1345 ◽  
Author(s):  
Kazuo Kitagawa ◽  
Masayasu Matsumoto ◽  
Takuma Mabuchi ◽  
Yoshiki Yagita ◽  
Toshiho Ohtsuki ◽  
...  

Recent evidence has shown crucial roles for cell-adhesion molecules in inflammation-induced rolling, adhesion, and accumulation of neutrophils in tissue. Intercellular adhesion molecule-1 (ICAM-1) is one of these adhesion molecules. Previous studies have shown marked reduction in the size of infarction after focal cerebral ischemia by depletion of granulocytes and administration of the antibody against ICAM-1. In the present study we investigated the role of ICAM-1 in the size of ischemic lesions, accumulation of granulocytes, and microcirculatory compromise in focal cerebral ischemia by using ICAM-1–knockout mice. Ischemic lesions were significantly mitigated in knockout mice after permanent and transient focal ischemia, even though the number of granulocytes in the infarcted tissue was almost the same between knockout and wild-type mice. Depletion of granulocytes further decreased the size of ischemic lesions after transient focal ischemia in ICAM-1–knockout mice. Microcirculation was reduced after focal ischemia, but it was better preserved in the cerebral cortex of knockout mice than that of wild-type mice. The present study demonstrated that ICAM-1 played a role in microcirculatory failure and subsequent development and expansion of infarction after focal cerebral ischemia. However, it is highly unlikely that ICAM-1 played a key role in accumulation of granulocytes after focal cerebral ischemia.


1996 ◽  
Vol 16 (4) ◽  
pp. 578-584 ◽  
Author(s):  
Michael Chopp ◽  
Yi Li ◽  
Ning Jiang ◽  
Rui Lan Zhang ◽  
Jonathan Prostak

We tested the hypothesis that treatment of transient focal cerebral ischemia in rat with antibodies directed against adhesion molecules reduces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon monofilament into the internal carotid artery. Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellular adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, animals were killed and the brains analyzed for ischemic cell damage, using hematoxylin and eosin (H/E); apoptosis, using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant reduction in the volume of infarction ( p < 0.01) and a decline in the absolute ( p < 0.001), and normalized (to the ischemic area, p < 0.05) numbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immunoreactive MPO cells were also reduced in the treatment groups compared to those in the control group ( p < 0.05). These data suggest that treatment with anti-adhesion molecule antibodies selectively reduce apoptosis, and that a contributing factor to the beneficial effect of antibody treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.


2019 ◽  
Vol 50 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Sonja Suvakov ◽  
Djurdja Jerotic ◽  
Tatjana Damjanovic ◽  
Natasa Milic ◽  
Tatjana Pekmezovic ◽  
...  

Introduction: Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. Methods: A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. Results: GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/­sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p < 0.001). Conclusion: We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Elisabetta Profumo ◽  
Brigitta Buttari ◽  
Daniela D’Arcangelo ◽  
Lavinia Tinaburri ◽  
Maria Antonietta Dettori ◽  
...  

Atherosclerosis is characterized by endothelial dysfunction, mainly induced by inflammation and oxidative stress. Increased reactive oxygen species (ROS) production together with increased adhesion molecules and thrombogenic tissue factor (TF) expression on endothelial cells has a key role in proatherogenic mechanisms. Therefore downmodulation of these molecules could be useful for reducing the severity of inflammation and atherosclerosis progression. Dehydrozingerone (DHZ) is a nutraceutical compound with anti-inflammatory and antioxidant activities. In this study we evaluated the ability of DHZ and its symmetric dimer to modulate hydrogen peroxide- (H2O2-) induced ROS production in human umbilical vein endothelial cells (HUVEC). We also evaluated intercellular adhesion molecule- (ICAM-) 1, vascular cell adhesion molecule- (VCAM-) 1, and TF expression in HUVEC activated by tumor necrosis factor- (TNF-)α. HUVEC pretreatment with DHZ and DHZ dimer reduced H2O2-induced ROS production and inhibited adhesion molecule expression and secretion. Of note, only DHZ dimer was able to reduce TF expression. DHZ effects were in part mediated by the inhibition of the nuclear factor- (NF-)κB activation. Overall, our findings demonstrate that the DHZ dimer exerts a potent anti-inflammatory, antioxidant, and antithrombotic activity on endothelial cells and suggest potential usefulness of this compound to contrast the pathogenic mechanisms involved in atherosclerosis progression.


2017 ◽  
Vol 8 (11) ◽  
pp. 4210-4216 ◽  
Author(s):  
Shuang Rong ◽  
Xueting Hu ◽  
Siqi Zhao ◽  
Yanting Zhao ◽  
Xiao Xiao ◽  
...  

Epidemiological studies strongly support the role of procyanidin-rich beverages and fruit in the prevention of cardiovascular diseases.


Author(s):  
Tamer E. Mosa ◽  
Mahmoud El-Sherbiny ◽  
Azza F. Arafa ◽  
Hisham A. Orban ◽  
Tarek E. Hodhod ◽  
...  

Leukocyte adhesion molecule-1 (LAM-1), CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) are adhesion molecules and constitute important steps in the liver inflammation due to chronic hepatitis C. We measured soluble intercellular adhesion molecule (LAM-1), (LFA-1) and (Mac-1) as well as cholesterol and triglyceride concentrations in the serum of 120 patients with fibrosis. A study was carried out to analyze levels of LAM-1, LFA-1 and Mac-1in fibrotic patients, and find whether increasing with cholesterol and triglycerides. 120 serum samples from fibrotic patients were classified according to levels of Cholesterol and Triglycerides concentration into four groups. Positive LAM-1 samples were found in 90% of patients in first group, 83% in the second group, 73% in the third group and 46% in the fourth group. These levels were significantly higher than their levels in control group (p<0.0001) indicating extremely significant. Level of LAM-1in group (1) was extremely significant compared to group (4) (356 ± 70.5 vs. 209± 5 p < 0.0001 ES). High LFA-1level was found in 76% in first group, 73% in the second group, 70% in the third group, and 40% in the fourth group. The levels of MAC-1 in first group were significantly greater than their levels in control group (p<0.0001), and +ve MAC-1 samples were found in 66% in first group, 53% in the second group, 46% in third group, and 36% in fourth group. AST and ALT were significantly higher in first group, compared to healthy group (95.68 ± 33.32 vs. 31.77 ± 8.11, p < 0.001) for AST and (78.6 ± 29.86 vs. 28.55 ± 7.15 p < 0.001) for ALT indicating very significant relationship, while no significant was detected between the fourth group and healthy individuals (33.56±8.16 vs. 28.55 ± 7.15 p = 0.05 NS). Our study showed a significant increase in levels of LAM-1 and LFA-1 rather than MAC-1 in fibrosis compared to healthy individuals. The results showed the ability to circulate LAM-1 and LFA-1 to predict fibrosis disease and evaluated the relationship between circulating adhesion molecules and fibrotic patients.


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