Lipid-lowering effect of molluscan (Katelysia opima) glycosaminoglycan (GAG) in hypercholesterolemic induced rats

2014 ◽  
Vol 395 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Vijayabaskar Pandian ◽  
Natarajan Aravindan ◽  
Sethupathy Subramanian ◽  
Somasundaram T. Somasundaran
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
High Fat ◽  
Lecithin Cholesterol Acyltransferase ◽  
Baseline Levels ◽  
Lipid Lowering Effect

Abstract Identifying pharmacologically safe lipid-lowering ‘deliverables’ could potentiate therapeutic outcome for diet-induced atherogenesis. Accordingly, we investigated the potential of molluscan (Katelysia opima) glycosaminoglycan (GAG) in modulating the early lipid changes in atherogenesis. Wistar rats were fed a diet with (n=24) or without (n=6) hypercholesterolemic atherogenic CCT (rat chow supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) for 17 days. CCT-fed rates were (i) treated with isolated molluscan GAG (40 mg/kg/day, s.c.) for 10 days after the introduction of CCT diet, (ii) cotreated with GAG (40 mg/kg/day, s.c.) for 17 days, or (iii) treated with heparin (200 units/kg/day, s.c.) for 10 days after the introduction of CCT. The increases induced by CCT diet in the plasma levels of cholesterol, triglycerides, high-density lipoprotein, very-low-density lipoprotein, and low-density lipoprotein were completely attenuated with GAG treatment. Consistently, alterations induced by CCT diet in the levels of plasma lecithin cholesterol acyltransferase and lipoprotein lipase activities were restored to baseline levels with GAG treatment. Coherently, histology revealed a decrease associated with GAG treatment in the CCT-diet-induced foam cells (in aorta), tubular damages (kidney), and lipid accumulations (liver). Together, these results suggest that GAG may exert antiatherogenesis potential by significantly attenuating lipid modulations derived by a high-fat diet. Further, the data imply that the GAG extracts may comprehensively prevent hypercholesterolemia-associated tissue damage and could thus serve as a therapeutic deliverable for hypercholesterolemia.

scholarly journals Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy

2018 ◽  
Vol 19 (12) ◽  
pp. 3903 ◽  
Author(s):  
Xiaofei Zhu ◽  
Jingyi Yang ◽  
Wenjuan Zhu ◽  
Xiaoxiao Yin ◽  
Beibei Yang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Sirtuin 1 ◽  
Lipid Lowering ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
High Fat ◽  
Density Lipoprotein Receptor

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

scholarly journals Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Liu ◽  
Chao Gao ◽  
Ping Yao ◽  
Zhiyong Gong
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Mrna And Protein Expression ◽  
Ldl Uptake ◽  
Underlying Mechanisms

A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved.

scholarly journals Indoleamine 2 3-dioxygenase knockout limits angiotensin II-induced aneurysm in low density lipoprotein receptor-deficient mice fed with high fat diet

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193737 ◽  
Author(s):  
Sarvenaz Metghalchi ◽  
Marie Vandestienne ◽  
Yacine Haddad ◽  
Bruno Esposito ◽  
Julien Dairou ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
High Fat ◽  
Indoleamine 2 ◽  
Density Lipoprotein Receptor ◽  
Deficient Mice

scholarly journals Cysteamine Decreases Low‐Density Lipoprotein Oxidation, Causes Regression of Atherosclerosis, and Improves Liver and Muscle Function in Low‐Density Lipoprotein Receptor–Deficient Mice

2021 ◽  
Vol 10 (18) ◽  
Author(s):  
Feroz Ahmad ◽  
Robert D. Mitchell ◽  
Tom Houben ◽  
Angela Palo ◽  
Tulasi Yadati ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Muscle Function ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Background We have shown previously that low‐density lipoprotein (LDL) can be oxidized in the lysosomes of macrophages, that this oxidation can be inhibited by cysteamine, an antioxidant that accumulates in lysosomes, and that this drug decreases atherosclerosis in LDL receptor–deficient mice fed a high‐fat diet. We have now performed a regression study with cysteamine, which is of more relevance to the treatment of human disease. Methods and Results LDL receptor–deficient mice were fed a high‐fat diet to induce atherosclerotic lesions. They were then reared on chow diet and drinking water containing cysteamine or plain drinking water. Aortic atherosclerosis was assessed, and samples of liver and skeletal muscle were analyzed. There was no regression of atherosclerosis in the control mice, but cysteamine caused regression of between 32% and 56% compared with the control group, depending on the site of the lesions. Cysteamine substantially increased markers of lesion stability, decreased ceroid, and greatly decreased oxidized phospholipids in the lesions. The liver lipid levels and expression of cluster of differentiation 68, acetyl–coenzyme A acetyltransferase 2, cytochromes P450 (CYP)27, and proinflammatory cytokines and chemokines were decreased by cysteamine. Skeletal muscle function and oxidative fibers were increased by cysteamine. There were no changes in the plasma total cholesterol, LDL cholesterol, high‐density lipoprotein cholesterol, or triacylglycerol concentrations attributable to cysteamine. Conclusions Inhibiting the lysosomal oxidation of LDL in atherosclerotic lesions by antioxidants targeted at lysosomes causes the regression of atherosclerosis and improves liver and muscle characteristics in mice and might be a promising novel therapy for atherosclerosis in patients.

scholarly journals Evaluation of antiatherogenic effect of Alternanthera brasiliana Linn kuntz in rats on atherogenic diet

2019 ◽  
Vol 8 (6) ◽  
pp. 1172
Author(s):  
Urmi Choudhury ◽  
Tarali Devi ◽  
Asha Borah
Keyword(s):  
High Density Lipoprotein ◽  
Total Cholesterol ◽  
High Fat Diet ◽  
Methanolic Extract ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Serum Total Cholesterol ◽  
Low Density ◽  
High Fat

Background: Hypercholesterolaemia is a major risk factor for systemic atherosclerosis and a well-known etiological factor for cardiovascular diseases and its complications which is a leading cause of mortality worldwide. In a recent study, the antihyperlipidemic activity of dried leaves extract of Alternanthera brasiliana has been evaluated. Hence, the present study was undertaken to investigate the anti-atherosclerotic potential of the methanolic extract of the leaves of Alternanthera brasiliana L. Kuntz (MEAB) in high fat diet induced hypercholesterolemic rat model.Methods: Thirty (30) wistar albino rats of either sex were randomly divided into five groups: first two groups received normal diet and high fat diet respectively and the remaining three groups received high fat diet supplemented with methanolic extract of Alternanthera brasiliana (MEAB) administered orally daily at two different doses: 200 mg/kg and 400 mg/kg and Atorvastatin 10 mg/kg/day orally as standard respectively. Serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) was estimated after 12 weeks. Atherogenic index was calculated from the results of lipid profile. At the end, the aorta was removed for assessment of atherosclerotic plagues.Results: Our results showed that MEAB possessed significant cholesterol lowering potency as indicated by decrease in serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL-C) accompanied by an increase in serum high density lipoprotein (HDL-C) and reduces the atherosclerotic lesion of aorta (p <0.05).Conclusions: These results strongly suggests that MEAB can prevent the progress of atherosclerosis likely due to the effect of A. brasiliana on serum lipoproteins and its antioxidant and anti-inflammatory properties. It could be a potential therapy for the prevention and treatment of atherosclerosis.

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