Full
Outline
To investigate the effects of Gualou Xiebai Banxia Decoction（瓜蒌薤白半夏汤，GXBD）on blood lipids，oxidized low-density lipoprotein（ox-LDL）and fecal bile acids in the model of early atherosclerosis（AS）in APOE gene knockout（Apoe-/-）mice and to explore the possible mechanisms of GXBD in the prevention and treatment of early AS.
TCMSP database was used to search the chemical constituents of GXBD，PharmMapper to predict the targets.GeneCards database was searched with “Atherosclerosis（AS）”as the search term to select the AS-related targets with a score of≥1，and DAVID database was used to analyze the intersecting targets for Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment.For the animal experiments of prevention-treatment mechanism，15 male Apoe-/- mice were randomly divided into 3 groups：control group（Group A，normal diet），high-fat diet model group（Group AF，high-fat diet），GXBD intervention group（Group AF-GL，high-fat diet，GXBD 10 g·kg-1·d-1），and the high-fat diets were fed for 8 weeks in order to prepare a mouse model for early stage of AS，wherein pharmacological interventions were initiated from the 5th week onwards to the end of the experiments.The serum levels of low-density lipoprotein（LDL），high-density lipoprotein（HDL），total cholesterol（TC）and triglycerides（TG），and concentrations of oxidized low-density lipoprotein（ox-LDL）in serum，liver and ileum were measured 4 hours after the last administration.The aorta was isolated for oil-red O staining.The mRNA levels of constitutive androstane receptors（CAR）and cholesterol 7α-hydroxylase（CYP7A1）of liver were detected and mRNA levels of fatty acid-binding protein（FABP6）in colon were detected，and fecal bile acids were measured.
Thirty-four active compounds of GXBD were obtained，and there were 164 intersecting targets with AS，which were mainly involved in lipid oxidation and signal transduction. Compared with those of group A，the AF group showed increased aortic lipid deposition，and the level of serum ox-LDL was significantly higher（P<0.01），the levels of mRNA expressions of CAR were significantly lower（P<0.05），the content of fecal primary bile acids was significantly higher（P<0.05），and the contents of secondary bile acids were significantly higher（P<0.05）. Compared with those of the AF group，aortic lipid deposition was reduced in the AF-GL group，serum ox-LDL levels were significantly decreased（P<0.01），the level of mRNA expression of CAR was significantly increased（P<0.05），and fecal primary bile acid content was significantly down-regulated（P<0.05）.
GXBD regulates lipid peroxidation by activating CAR and CYP7A1 in liver to promote bile acid metabolism，accelerating cholesterol catabolism to regulate oxidized lipids，lowering ox-LDL，and preventing and treating early AS.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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