Abstract

Hypercholesterolemia is a metabolic disorder associated with oxidative stress. The present study investigated the protective effect of Monolluma quadrangula extract on hypercholesterolemia-induced oxidative stress in the liver and heart of high-cholesterol-diet- (HCD-) fed rats. The experimental animals received HCD for 10 weeks and were concurrently treated with 300 or 600 mg/kg M. quadrangula extract. HCD-fed rats showed a significant increase in serum triglycerides, total cholesterol, LDL-cholesterol, vLDL-cholesterol, and cardiovascular risk indices along with decreased HDL-cholesterol and antiatherogenic index. The M. quadrangula extract significantly improved dyslipidemia and atherogenesis in HCD-fed rats. HCD induced a significant increase in serum transaminases, creatine kinase-MB, and proinflammatory cytokines. In addition, HDC induced a significant increase in hepatic and cardiac lipid peroxidation and decreased antioxidant enzymes. Treatment with the M. quadrangula extract significantly alleviated liver and heart function markers, decreased proinflammatory cytokines and lipid peroxidation, and enhanced the antioxidant defenses. Also, the M. quadrangula extract significantly reduced the expression of fatty acid synthase (FAS) and increased the expression of LDL receptor in the liver of HCD-fed rats. In conclusion, the M. quadrangula extract has a potent antihyperlipidemic and cholesterol-lowering effect on HCD-fed rats. The beneficial effects of the M. quadrangula extract were mediated through the increased antioxidant defenses, decreased inflammation and lipid peroxidation, and modulated hepatic FAS and LDL receptor gene expression.

Highlights

  • Hyperlipidemia is a lipid metabolism disorder associated with the development of atherosclerosis and cardiovascular disease [1, 2]

  • HCD-induced rats treated with 300 and 600 mg/kg M. quadrangula extract showed a significant (P < 0 001) alleviation in serum levels of triglycerides, total cholesterol, lowdensity lipoprotein (LDL)-cholesterol, and vLDLcholesterol, while this treatment had a nonsignificant effect on serum HDL-cholesterol levels

  • Hypercholesterolemia has been reported to be implicated in protein glycation, oxidative modification of LDL, and lipid peroxidation [29]

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Summary

Introduction

Hyperlipidemia is a lipid metabolism disorder associated with the development of atherosclerosis and cardiovascular disease [1, 2]. Studies have reported that hyperlipidemia, hypercholesterolemia, leads to atherosclerosis which is a chronic inflammatory status initiated by subendothelial retention and oxidation of lowdensity lipoprotein (LDL) cholesterol [4]. Dyslipidemia/hypercholesterolemia leads to increased accumulation of lipids in the liver, reducing its ability to lower blood lipids [2]. Cholesterol accumulation in endothelial cells, hepatocytes, leukocytes, erythrocytes, and platelets provokes the production of reactive oxygen species (ROS) and reduces antioxidant defenses [7, 8]. This can lead to redox imbalance, oxidative stress, and metabolic alterations [9, 10]. Agents that combine lipid-lowering and antioxidant potentials can prevent the negative impact of cholesterol on the liver, heart, and other body tissues

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