Abstract
Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) oxidation are well known to increase the risk for atherosclerosis. In our ongoing research on natural products with inhibitory activities against oxidation of lipoproteins, fruits of Vitex rotundifolia were found to be highly active. There is no report on the effects on LDL and HDL oxidation. Herein, we investigated the inhibitory effects of V. rotundifolia fruit extract and its six compounds, which are: (1) artemetin, (2) casticin, (3) hesperidin, (4) luteolin, (5) vitexin, and (6) vanillic acid, against LDL and HDL oxidation. The LDL and HDL oxidations were determined by measuring production of conjugated dienes and thiobarbituric acid reactive substances, amount of hyperchromicity and carbonyl content, change in electrical charge, and apoA-I aggregation. In addition, the contents of the compounds in the extracts were analyzed using HPLC-DAD. Consequently, extracts of Vitex rotundifolia fruits and compounds 2 and 4 suppressed oxidation of LDL and HDL, showing inhibition of lipid peroxidation, decrease of negative charges in lipoproteins, reduction of hyperchromicity, decrease in carbonyl contents, and prevention of apoA-I aggregation. In particular, compounds 2 and 4 exhibited more potent inhibitory effect on oxidation of LDL and HDL than the extracts, suggesting their protective role against atherosclerosis via inhibition of LDL and HDL oxidation. The contents of artemetin, casticin, and vanillic acid in the extracts were 1.838 ± 0.007, 8.629 ± 0.078, and 1.717 ± 0.006 mg/g, respectively.
Highlights
Atherosclerosis is the narrowing and stiffening of the arteries, caused by the accumulation of cholesterol, fatty substances, calcium, and other substances in the inner walls of the arteries, which is the usual cause of heart attack, heart failure, cardiac ischemia, stroke, and peripheral vascular disease, and is the leading cause of morbidities and mortalities worldwide [1,2]
Even low concentrations of compounds 2 and 4 powerfully restricted the generation of Conjugated Dienes (CD) and MDA (Figure 2E,F and Figure 3E,F). These results indicated that V. rotundifolia fruit extract and compounds 2 and 4 could suppress lipid peroxidation through inhibiting CD and MDA formation on copper-mediated oxidized Low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
2 and 4 showed the most potent activities even at low concentrations (Figure 7E,F). These results suggested that V. rotundifolia fruit extract and compounds 2 and 4 remarkably can aid to prevent dysfunctional HDL formation
Summary
Atherosclerosis is the narrowing and stiffening of the arteries, caused by the accumulation of cholesterol, fatty substances, calcium, and other substances in the inner walls of the arteries, which is the usual cause of heart attack, heart failure, cardiac ischemia, stroke, and peripheral vascular disease, and is the leading cause of morbidities and mortalities worldwide [1,2]. Many studies have been conducted to investigate the relationship between incidence of atherosclerosis and lipoproteins [3,4]. LDL is the main blood carrier of cholesterol for delivery to peripheral tissues, while HDL mediates the reverse cholesterol transport, which is the process of cholesterol movement from tissues back to the liver, and these transport processes are necessary for efficient homeostasis of cholesterol in the human body [5]. The levels of LDL or HDL and their modification act as an atherosclerotic risk factor, and are associated with an increased incidence of atherosclerosis. Many studies have reported that the elevation of serum LDL level and its oxidation are strongly related with an increased risk of developing atherosclerosis [6,7].
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