Xiang-Bao Meng1, Ting Zhu1, De-Hui Yang2, Wei Liang2, Gui-Bo Sun1, Xiao-Bo Sun1. 1. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. 2. Dongfang Pharmaceutical Co. Ltd., Jilin 130000, China.
Abstract
BACKGROUND: Xuezhitong capsules (XZT) are derived from Xie Bai and used for abnormal lipid homeostasis treatment through maintained metabolic balance. However, their mechanisms are largely unknown. Here, we mainly assessed the contribution of reverse cholesterol transport (RCT) and the accompanying increase in the high-density lipoprotein (HDL) effects of XZT to cholesterol dysfunction amelioration in mice. METHODS: We assessed serum lipids by using enzymatic kits. We observed atherosclerotic plaque formation by hematoxylin-eosin (HE) and Oil Red O staining. We studied the lipid metabolism, fatty acid synthase (FAS), HDL, low-density lipoprotein receptor (LDLR), triglyceride (TG) metabolic enzyme expression levels, and RCT function in various tissues upon stimulation with high-fat diet, XZT, and some positive drugs by ELISA. RESULTS: After 34 weeks of high-fat diet administration, blood lipids levels increased because attenuated by XZT treatment (800 and 1,600 mg/kg, i.g.). XZT improved the lipid metabolism instability, induced RCT activation, and subsequently increased the HDL levels in hyperlipidemic mice (P<0.05). FAS (P<0.05) and LDLR (P<0.01) levels also remarkably improved. The effects of XZT were closely associated with RCT activation and the accompanying increase in the HDL levels, as characterized by XZT-induced preservation in ATP-binding cassette transporter member 1 (ABCA1), scavenger receptor class B type 1 (SRB1), acyl coenzyme A: cholesterol acyltransferase (ACAT), lecithin cholesterol acyltransferase (LCAT), apolipoprotein A I (ApoA1) and apolipoprotein B (ApoB). However, XZT showed no effect on high fat diet-activated TG metabolic enzyme expression levels (P>0.05). CONCLUSIONS: XZT are promising drugs in balancing the cholesterol dysfunction from hyperlipidemia through RCT activation and accompanying increase in HDL levels.
BACKGROUND: Xuezhitong capsules (XZT) are derived from Xie Bai and used for abnormal lipid homeostasis treatment through maintained metabolic balance. However, their mechanisms are largely unknown. Here, we mainly assessed the contribution of reverse cholesterol transport (RCT) and the accompanying increase in the high-density lipoprotein (HDL) effects of XZT to cholesterol dysfunction amelioration in mice. METHODS: We assessed serum lipids by using enzymatic kits. We observed atherosclerotic plaque formation by hematoxylin-eosin (HE) and Oil Red O staining. We studied the lipid metabolism, fatty acid synthase (FAS), HDL, low-density lipoprotein receptor (LDLR), triglyceride (TG) metabolic enzyme expression levels, and RCT function in various tissues upon stimulation with high-fat diet, XZT, and some positive drugs by ELISA. RESULTS: After 34 weeks of high-fat diet administration, blood lipids levels increased because attenuated by XZT treatment (800 and 1,600 mg/kg, i.g.). XZT improved the lipid metabolism instability, induced RCT activation, and subsequently increased the HDL levels in hyperlipidemic mice (P<0.05). FAS (P<0.05) and LDLR (P<0.01) levels also remarkably improved. The effects of XZT were closely associated with RCT activation and the accompanying increase in the HDL levels, as characterized by XZT-induced preservation in ATP-binding cassette transporter member 1 (ABCA1), scavenger receptor class B type 1 (SRB1), acyl coenzyme A: cholesterol acyltransferase (ACAT), lecithin cholesterol acyltransferase (LCAT), apolipoprotein A I (ApoA1) and apolipoprotein B (ApoB). However, XZT showed no effect on high fat diet-activated TG metabolic enzyme expression levels (P>0.05). CONCLUSIONS: XZT are promising drugs in balancing the cholesterol dysfunction from hyperlipidemia through RCT activation and accompanying increase in HDL levels.
Entities:
Keywords:
ATP-binding cassette transporter member 1 (ABCA1); Xuezhitong; hyperlipidemia; reverse cholesterol transport (RCT); scavenger receptor class B type 1 (SRB1)
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