Abstract
Xuezhikang (XZK), an extract of Chinese red yeast rice, is recommended as an optimal choice for patients with coronary heart disease (CHD) with markedly elevated triglyceride (TG) levels. This study was designed to compare the hypotriglyceridemic effects between XZK and simvastatin. The role of apolipoprotein A5 (apoA5), a key regulator of TG metabolism and a target gene of peroxisome proliferator-activated receptor α (PPARα), was to be identified in XZK-related hypotriglyceridemic actions. For these goals, hypertriglyceridemia of rats was induced by a high-fructose diet. In order to investigate the hypotriglyceridemic effects of XZK and simvastatin on these animals based on an equivalent low-density lipoprotein cholesterol (LDL-C) lowering power, we titrated their doses (XZK 80 mg/kg/d versus simvastatin 1 mg/kg/d) according to plasma LDL-C reduction of rats. Similarly, we titrated the target doses of the two agents (XZK 500 μg/ml versus simvastatin 10 μM) according to hepatocyte LDL receptor expressions, and then compared the effects of the two agents on TG and apoA5 of hepatocytes in vitro. Our results showed that XZK (80 mg/kg/d) had higher hypotriglyceridemic performance than simvastatin (1 mg/kg/d) on these animals albeit their equivalent LDL-C lowering power. Higher plasma apoA5 levels and hepatic apoA5 expressions were observed in rats treated with XZK (80 mg/kg/d) than simvastatin (1 mg/kg/d). Further, XZK (80 mg/kg/d) contributed to higher hepatic PPARα expressions of rats than simvastatin (1 mg/kg/d). Although the two agents led to an equivalent up-regulation of LDL receptors of hepatocytes, more TG reduction and apoA5 elevation were detected in hepatocytes treated with XZK (500 μg/ml) than simvastatin (10 μM). However, PPARα knockdown eliminated the above effects of XZK on hepatocytes. Therefore, our study indicates that XZK has greater hypotriglyceridemic performance than simvastatin in the setting of an equivalent LDL-C lowering power, which is attributed to more apoA5 up-regulation by this agent via the PPARα signaling pathway.
Highlights
Lipid disorders are well-acknowledged as important risks for the pathogenesis of coronary heart disease (CHD)
Elevated low-density lipoprotein cholesterol (LDL-C) represents a major contributor for CHD [1], it is frequently observed that plasma triglyceride (TG) levels still remain high in some CHD patients despite their satisfactory reduction of LDL-C by statins, a widely-prescribed class of lipid-lowering medications that reduce atherosclerotic cardiovascular risk primarily via LDL-C reduction [1]
Cell experiments were conducted as we described previously [16], with the following exception: Considering the fact that LDL-C cannot be measured in cultured hepatocytes in vitro and LDL receptor (LDL-R) on hepatocytes plays a key role in statin-related LDL-C reduction [17], hepatocyte LDL-R protein expressions by Western blot analysis were used as an index to titrate the target doses of the two agent (XZK 500 μg/ml versus simvastatin 10 μg/ml) for an equivalent LDL-C lowering power in vitro
Summary
Lipid disorders are well-acknowledged as important risks for the pathogenesis of coronary heart disease (CHD). Elevated low-density lipoprotein cholesterol (LDL-C) represents a major contributor for CHD [1], it is frequently observed that plasma triglyceride (TG) levels still remain high in some CHD patients despite their satisfactory reduction of LDL-C by statins ( known as HMG-CoA reductase inhibitors), a widely-prescribed class of lipid-lowering medications that reduce atherosclerotic cardiovascular risk primarily via LDL-C reduction [1]. This remaining TG elevation of CHD patients after statin therapy has been demonstrated to increase their residual cardiovascular risks [2]. No relevant studies have been designed to compare their hypotriglyceridemic performance between XZK and a low-intensity statin
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