Silibinin augments the effect of clopidogrel on atherosclerosis in diabetic ApoE deficiency mice

2021 ◽  
pp. 1-9
Author(s):  
Jianbo Zhang ◽  
Qiyu Shi ◽  
Yamin Hu ◽  
Xiaohong Li
Keyword(s):  
High Fat Diet ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Protective Effects ◽  
High Fat ◽  
Antithrombotic Effect ◽  
Aortic Lesion ◽  
Atherosclerosis Treatment ◽  
Oil Red O Staining ◽  
Oil Red O

BACKGROUND: Diabetes mellitus (DM) abolishes the antithrombotic effect of Clopidogrel. Here, we investigated the synergistic effect of Silibinin on Clopidogrel-mediated atherosclerosis treatment in diabetic mice. METHODS: ApoE–/– mice were fed with high-fat diet (HFD) to establish the atherosclerotic model with diabetes. Animals were treated with Clopidogrel, Silibinin, or the combined to evaluate the protective effects on atherosclerosis and diabetes through Oil-red-O staining, qRT-PCR, Western blot, and metabolic measurements. Platelet activation and aggregation ex vivo assays were performed to detect the anti-thrombotic effect of different administrations. RESULTS: Silibinin significantly enhanced the inhibitory effect of Clopidogrel on atherosclerosis in DM mice. Co-administration of Silibinin with Clopidogrel remarkedly reduced the aortic lesion, inflammation, and endothelial dysfunction in aorta roots, and diabetic symptoms were significantly improved by the Silibinin-Clopidogrel treatment in HFD-fed ApoE–/– mice. Interestingly, the anti-thrombotic effect of Clopidogrel was further augmented by the Silibinin treatment in atherosclerotic mice. CONCLUSION: In atherosclerotic mouse model, Silibinin significantly improves the effect of Clopidogrel on atherosclerosis.

scholarly journals Dietary supplementation with blueberry partially restores T-cell-mediated function in high-fat-diet-induced obese mice

2018 ◽  
Vol 119 (12) ◽  
pp. 1393-1399 ◽  
Author(s):  
Erin D. Lewis ◽  
Zhihong Ren ◽  
Jason DeFuria ◽  
Martin S. Obin ◽  
Simin N. Meydani ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Immune Function ◽  
High Fat Diet ◽  
Ex Vivo ◽  
T Cell Proliferation ◽  
Protective Effects ◽  
High Fat ◽  
Con A ◽  
Inflammatory Status

AbstractBlueberry, rich in antioxidant and anti-inflammatory phytochemicals, has been demonstrated to lower inflammatory status in adipose induced by high-fat diet (HFD) and obesity. The effect of blueberry on systemic immune functions has not been examined. C57BL/6 mice were randomised to one of three diets – low-fat diet (LFD), HFD and HFD plus 4 % (w/w) blueberry (HFD+B) – for 8 or 12 weeks. Ex vivo T-cell mitogens (concanavalin A (Con A); phytohaemagglutinin), T-cell antibody (anti-CD3; anti-CD3/CD28)-stimulated T-cell proliferation and cytokine production were assessed. After 8 weeks, both HFD groups weighed more (>4 g) than the LFD group; after 12 weeks, HFD+B-fed mice weighed more (>6 g) and had 41 % more adipose tissue than HFD-fed mice (P<0·05). After 12 weeks, T-cell proliferation was less in both HFD groups, compared with the LFD group. HFD-associated decrements in T-cell proliferation were partially (10–50 %) prevented by blueberry supplementation. At 12 weeks, splenocytes from HFD mice, but not from HFD+B mice, produced 51 % less IL-4 (CD3/CD28) and 57 % less interferon-γ (Con A) compared with splenocytes from LFD mice (P<0·05). In response to lipopolysaccharide challenge, splenocytes from both HFD groups produced 24–30 % less IL-6 and 27–33 % less TNF-α compared with splenocytes from LFD mice (P<0·05), indicating impaired acute innate immune response. By demonstrating deleterious impacts of HFD feeding on T-cell proliferation and splenocyte immune responses, our results provide insights into how HFD/obesity can disrupt systemic immune function. The protective effects of blueberry suggest that dietary blueberry can buttress T-cell and systemic immune function against HFD-obesity-associated insults.

scholarly journals Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Jiaxin Zhang ◽  
Haixia Du ◽  
Menglan Shen ◽  
Zhengqi Zhao ◽  
Xinmiao Ye
Keyword(s):  
Signaling Pathway ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
High Fat ◽  
Oil Red O Staining ◽  
Oil Red O

Kangtaizhi granule (KTZG) is a Chinese medicine compound prescription and has been proven to be effective in nonalcoholic fatty liver disease (NAFLD) treatment clinically. However, the underlying mechanisms under this efficacy are rather elusive. In the present study, network pharmacology and HPLC analysis were performed to identify the chemicals of KTZG and related target pathways for NAFLD treatment. Network pharmacology screened 42 compounds and 79 related targets related to NAFLD; HPLC analysis also confirmed six compounds in KTZG. Further experiments were also performed. In an in vivo study, SD rats were randomly divided into five groups: control (rats fed with normal diet), NAFLD (rats fed with high-fat diet), and KTZG 0.75, 1.5, and 3 groups (NAFLD rats treated with KTZG 0.75, 1.5, and 3 g/kg, respectively). Serum lipids were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE and oil red O staining. In an in vitro study, HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without KTZG treatment. MTT assay, intracellular TG level, oil red O staining, and glucose uptake in cells were detected. Western blotting and immunohistochemical and immunofluorescence staining were also performed to determine the expression of lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 and genes in the AMPK/mTOR signaling pathway. In high-fat diet-fed rats, KTZG treatment significantly improved liver organ index and serum lipid contents of TG, TC, LDL-C, HDL-C, ALT, and AST significantly; HE and oil red O staining also showed that KTZG alleviated hepatic steatosis and liver lipid accumulation. In FFA-treated HepG2 cells, KTZG treatment decreased the intracellular TG levels, lipid accumulation, and attenuated glucose uptake significantly. More importantly, lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 expressions were ameliorated with KTZG treatment in high-fat diet-fed rats and FFA-induced HepG2 cells. The p-AMPK and p-mTOR expressions in the AMPK/mTOR signaling pathway were also modified with KTZG treatment in high-fat diet-fed rats and HepG2 cells. These results indicated that KTZG effectively ameliorated lipid accumulation and hepatic steatosis to prevent NAFLD in high-fat diet-fed rats and FFA-induced HepG2 cells, and this effect was associated with the AMPK/mTOR signaling pathway. Our results suggested that KTZG might be a potential therapeutic agent for the prevention of NAFLD.

scholarly journals Panax Notoginseng Protects against Diabetes-Associated Endothelial Dysfunction: Comparison between Ethanolic Extract and Total Saponin

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xutao Zhang ◽  
Chunxiu Zhou ◽  
Lingchao Miao ◽  
Yi Tan ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
High Glucose ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Ethanolic Extract ◽  
Panax Notoginseng ◽  
Protective Effects ◽  
High Fat ◽  
And Oxidative Stress

Previous studies revealed a cardioprotective potential of Panax notoginseng to relieve acute myocardial infarction and focal cerebral ischemia-reperfusion. However, whether P. notoginseng protects endothelial function in diabetes and the underlying mechanisms remain to be explored. P. notoginseng contains several chemical components including saponins, which are commonly believed as the major bioactive ingredients. The present study was aimed to examine and compare the vaso-protective effects of the ethanolic extract of P. notoginseng (PNE) and total saponin (PNS). Both aortas and carotid arteries were isolated from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) with and without the presence of PNS and PNE. Diabetic model was established by feeding the mice with a high-fat diet (45% kcal% fat) for 12 weeks, while PNS and PNE were administrated by oral gavage at 20 mg/kg/day for another 4 weeks. Ex vivo exposure to high glucose impaired acetylcholine-induced endothelium-dependent relaxations in mouse aortas, decreased phosphorylation of AMPK and eNOS, and induced endoplasmic reticulum (ER) stress and oxidative stress. These effects were reversed by cotreatment of PNS and PNE with PNS being more potent. Furthermore, the vaso-protective effects were abolished by Compound C (AMPK inhibitor). Chronic treatment with PNS and PNE improved endothelium-dependent relaxations and alleviated ER stress and oxidative stress in aortas from high-fat diet-induced obese mice. PNE was more effective to improve glucose sensitivity and normalize blood pressure in diabetic mice. The present results showed that PNS and PNE reduced ER stress and oxidative stress and, subsequently, improved endothelial function in diabetes through AMPK activation. This study provides new inspiration on the therapeutic potential of P. notoginseng extract against vascular diseases associated with metabolic disorders.

scholarly journals Effect of BuShen JiangZhi Recipe on Atherosclerosis in ApoE−/- Mice by Regulating the Expression of Anpep via mmu_circRNA_22187

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Li Yan ◽  
Qingling Jia ◽  
Hui Cao ◽  
Pingyi He ◽  
Sanli Xing ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Control Group ◽  
High Fat ◽  
Aortic Sinus ◽  
Version 2.0 ◽  
Oil Red O Staining ◽  
Oil Red O

The BuShen JiangZhi (BSJZ) recipe is a Chinese medicine compound with the effect of tonifying the kidney, replenishing essence, and lowering blood fat to unblock vessels. The purpose of this study is to explore whether the mechanism of BSJZ for effective intervention in the treatment of AS is related to mmu_circRNA_22187 and aminopeptidase N (Anpep). ApoE-/- mice were induced by a high-fat diet to replicate the AS model. 24 ApoE-/- mice were randomly divided into model group (group M), BSJZ group (group BS), and 12 C57BL/6 mice of the same genetic background and same weeks of age as the normal control group (group C). Mice in the BS group were given an aqueous solution of BSJZ by gavage, while mice in groups C and M were given the same volume of distilled water. HE and Oil Red O staining were used to detect the pathomorphology and lipid accumulation of mouse aortic sinus. Arraystar version 2.0 mouse circRNA chip was used to scan with Agilent Scanner G2505C, and the differential circRNAs expression profile of mice aorta was obtained. Scatter plot, volcano plot, and cluster map, respectively, visualized the differentially expressed circRNAs, as well as the types of circRNAs and the chromosomes’ distribution, screened and compared the differentially expressed circRNAs intersection between groups by Venny software, and then combined ceRNA bioinformatics analysis to construct a ceRNA network. The results showed that BSJZ could significantly reduce the area of AS plaque and lipid accumulation in the aortic sinus of ApoE-/- mice induced by a high-fat diet. The bioinformatics analysis showed that mmu_circRNA_22187 may be a key circRNA of BSJZ intervention in the treatment of AS. Compared with group C, the expressions of Anpep mRNA and protein were upregulated in group M. After the intervention of BSJZ, the expressions of Anpep mRNA and protein were downregulated. Therefore, BSJZ could effectively treat AS which might be related to the regulation of mmu_circRNA_22187 and Anpep.

scholarly journals Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle

2018 ◽  
Vol 45 (3) ◽  
pp. 1136-1148 ◽  
Author(s):  
Guoyou Chen ◽  
Guozhu Ye ◽  
Xinbo Zhang ◽  
Xiaoxiao Liu ◽  
Yingfeng Tu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Risk Factors ◽  
High Fat Diet ◽  
Abdominal Muscle ◽  
Abdominal Muscles ◽  
Metabolic Risk ◽  
High Fat ◽  
Intracellular Lipid ◽  
Oil Red O Staining ◽  
Oil Red O

Background/Aims: Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis. Methods: The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively. Results: The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group. Conclusions: We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.

scholarly journals Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet

2021 ◽  
Author(s):  
Joe W. E. Moss ◽  
Jessica O Williams ◽  
Wijdan Al-Ahmadi ◽  
Victoria O'Morain ◽  
Yee-Hung Chan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
High Fat Diet ◽  
Inflammatory Disorder ◽  
Protective Effects ◽  
Unique Combination ◽  
Omega 3 ◽  
High Fat ◽  
Food Ingredients

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3...

The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice

2021 ◽  
Vol 32 (4) ◽  
pp. 637-644
Author(s):  
Jamal Nasser Saleh Al-maamari ◽  
Mahardian Rahmadi ◽  
Sisca Melani Panggono ◽  
Devita Ardina Prameswari ◽  
Eka Dewi Pratiwi ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Inhibitory Effect ◽  
Pcr Analysis ◽  
Regulator Gene ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Reverse Transcription Pcr ◽  
Hematoxylin Eosin ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives The study aimed to determine the effect of quercetin on the expression of primary regulator gene involved in lipogenesis and triglycerides synthesis in the liver, and the sterol regulatory binding protein-1c (SREBP-1c) mRNA in non-alcoholic fatty liver disease (NAFLD) with a high-fat diet (HFD) model. Methods Fifty-six Balb/c mice were divided into seven groups: standard feed; HFD; HFD and quercetin 50 mg/kg for 28 days; HFD and quercetin 100 mg/kg BW for 28 days; HFD and quercetin 50 mg/kg for 14 days; HFD and quercetin 100 mg/kg for 14 days; HFD and repaired fed for 14 days. Quercetin was administered intraperitoneally. The animals were sacrificed 24 h after the last treatment; the liver was taken for macroscopic, histopathological staining using hematoxylin–eosin and reverse transcription-PCR analysis sample. Results HFD significantly increased the expression of SREBP-1c mRNA; meanwhile, quercetin and repaired feed significantly reduced the expression of SREBP-1c mRNA in the liver. Quercetin at a dose of 50 mg/kg and 100 mg/kg also improved liver cells’ pathological profile in high-fat diet NAFLD. Conclusions The present study suggests that quercetin has an inhibitory effect on SREBP-1c expression and improved liver pathology in NAFLD mice.

scholarly journals Liver and intestinal protective effects of Castanea sativa Mill. bark extract in high-fat diet rats

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0201540 ◽  
Author(s):  
Roberta Budriesi ◽  
Fabio Vivarelli ◽  
Donatella Canistro ◽  
Rita Aldini ◽  
Clara Babot Marquillas ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Castanea Sativa ◽  
Bark Extract ◽  
Protective Effects ◽  
High Fat ◽  
Castanea Sativa Mill

scholarly journals Mangosteen Pericarp Inhibits Nuclear Factor ?B (NF-?B) Activation and Reduces Expression of ICAM-1 in High Cholesterol Diet Rat

2013 ◽  
pp. 23-32
Author(s):  
H Hendarto ◽  
Mohammad Saifur Rohman ◽  
Djanggan Sargowo
Keyword(s):  
Crude Extract ◽  
High Fat Diet ◽  
Inhibitory Effect ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Factor B ◽  
Underlying Risk Factor ◽  
Underlying Risk

Background: Atherosclerosis is widely viewed as an inflammatory disease with hypercholesterolemia being a dominant underlying risk factor. This study aimed to determine the effect of mangosteen pericarp in inhibition of NF-?B activation and ICAM-1 expression in rat fed with high cholesterol.Methods and Results: Various doses of crude extract mangosteen pericarp were administered to the high fat diet wistar rats and the activity of NF-?B measured by immunohistochemistry to assess nuclear NF-?B expression and the ICAM-1 expression. The high fat diet resulted significant increased serum LDL levels. Increased nuclear NF- ?B activation and ICAM-1 expression were also observed in high fat diet rats in concurrence with increased serum LDL. The inhibitory effect on NF- ?B activity and ICAM-1 expression was observed when 400 mg of mangosteen pericarp crude extract was administered and even showed a higher inhibitory effect in 800 mg of mangosteen pericap treated rats. The 800 mg extract treatment resulted in decreased ICAM-1 expression similar to those of non high fat rats.Conclusion: The administration of 800 mg mangosteen pericarp crude extract significantly inhibited NF-?B activation and reversed the expression of ICAM -1 to the normal level in high cholesterol diet rats.

scholarly journals Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3607
Author(s):  
Bojan Stojnić ◽  
Alba Serrano ◽  
Lana Sušak ◽  
Andreu Palou ◽  
M. Luisa Bonet ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Beta Carotene ◽  
Protective Effects ◽  
High Fat ◽  
Cumulative Energy ◽  
Brown Adipose ◽  
Obesogenic Diet ◽  
Cumulative Energy Intake

Anti-obesity activity has been reported for beta-carotene (BC) supplementation at high doses and metformin (MET). We studied whether BC treatment at a closer to dietary dose and MET treatment at a lower than therapeutic dose are effective in ameliorating unwanted effects of an obesogenic diet and whether their combination is advantageous. Obesity-prone mice were challenged with a high-fat diet (HFD, 45% energy as fat) for 4 weeks while receiving a placebo or being treated orally with BC (3 mg/kg/day), MET (100 mg/kg/day), or their combination (BC+MET); a fifth group received a placebo and was kept on a normal-fat diet (10% energy as fat). HFD-induced increases in body weight gain and inguinal white adipose tissue (WAT) adipocyte size were attenuated maximally or selectively in the BC+MET group, in which a redistribution towards smaller adipocytes was noted. Cumulative energy intake was unaffected, yet results suggested increased systemic energy expenditure and brown adipose tissue activation in the treated groups. Unwanted effects of HFD on glucose control and insulin sensitivity were attenuated in the treated groups, especially BC and BC+MET, in which hepatic lipid content was also decreased. Transcriptional analyses suggested effects on skeletal muscle and WAT metabolism could contribute to better responses to the HFD, especially in the MET and BC+MET groups. The results support the benefits of the BC+MET cotreatment.

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