Abstract

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.

Highlights

  • Hemin can be detected in the serum of β-thalassemia/hemoglobin (β-thal/HbE) patients, vascular complications and early atherosclerosis commonly occurred in these patients [6]

  • thiobarbituric reactive substance (TBARs) formation was gradually increased after depletion of αtocopherol

  • This study showed that lusianthridin reduced foam cell formation (Figure 5) and it can be assumed that lusianthridin possibly inhibits the engulfment of he-oxLDL by scavenger receptors of RAW 264.7 macrophage cells

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Summary

Introduction

Atherosclerosis is a chronic disease of the arterial wall. Oxidation of low-density lipoprotein (LDL) plays a significant role in the initiation and development of atherosclerosis [1]. LDL can be oxidized by transition metals, such as iron [2] and hemin [3]. Metal iron-induced oxidation is essential in lipid peroxidation and protein oxidations of lipoproteins [4]. Hemin (iron III -protoporphyrin IX), the degradation product of hemoglobin oxidation, appears in the plasma because of intravascular hemolysis [5]. Hemin can be detected in the serum of β-thalassemia/hemoglobin (β-thal/HbE) patients, vascular complications and early atherosclerosis commonly occurred in these patients [6]. The ferric component of hemin penetrates the hydrophobic core of LDL [7] and causes LDL

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