ABSTRACT
ObjectiveTo explore the mechanism of Shenqi Gualou Xiebai Banxia Decoction （参芪瓜蒌薤白半夏汤， SGXBD） in the treatment of atherosclerosis. MethodsThirty Apolipoprotein E gene knockout （ApoE-/-） mice were randomly divided into five groups： model group， rosuvastatin group， low-， moderate-， and high-dose SGXBD， with six mice in each group. They were fed a high-fat diet to prepare for atherosclerosis model. Another six C57BL/6J wild-type mice were set as the blank group. After modeling， the low-， moderate-， and high-dose SGXBD groups were gavaged with 6.46， 12.92， and 25.84 g/（kg·d） of SGXBD， respectively. The rosuvastatin group was given 1.55 mg/（kg·d） of rosuvastatin tablets by gavage. The blank group and model group were given 0.5 ml saline by gavage. After four weeks， the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum of each group were detected， as well as TC and TG in the liver. The serum bile acid level was detected by enzyme cycling colorimetry. The mRNA and protein expression of peroxisome proliferator-activated receptor γ （PPARγ）， sterol regulatory element-binding protein 2 （SREBP2）， 3-hydroxy-3-methylglutaryl-CoA reductase （HMGCR）， and cholesterol 7α-hydroxylase （CYP7A1） in the liver were detected by real-time RT-PCR and Western blot. ResultsCompared with the blank group， the model group showed significant increases in serum TG， TC， and LDL-C levels， and significant decreases in HDL-C and bile acid levels； the levels of TG and TC in the liver， as well as the expression of SREBP2 and HMGCR proteins and mRNA in the liver significantly increased， while the expression of PPARγ and CYP7A1 proteins and mRNA significantly decreased （all P＜0.01）. Compared with the model group， the rosuvastatin group and high-dose SGXBD group showed significant decreases in serum TG， TC， and LDL-C levels and liver TG and TC levels， and significant increases in bile acid levels； the expression of PPARγ and CYP7A1 proteins and mRNA increased， while the expression of SREBP2 and HMGCR proteins and mRNA decreased； the low-dose SGXBD group showed significant decreases in serum TC and LDL-C levels and liver TC level （P＜0.05 or P＜0.01）. Compared with the rosuvastatin group， the low-dose SGXBD group had a significantly higher liver TC level， while the high-dose SGXBD group had a significantly lower liver TC level， CYP7A1 mRNA level， and PPARγ protein expression level， and a significantly higher SREBP2 protein expression level （P＜0.05 or P＜0.01）. Compared with the low- and moderate-dose groups， the high-dose SGXBD group had significantly lower serum TG and liver TC levels （P＜0.05）. ConclusionSGXBD may improve blood lipid levels and exhibit anti-atherosclerotic effects by regulating the protein level of PPARγ and simultaneously affecting the synthesis of liver cholesterol and the conversion of cholesterol to bile acids.
ABSTRACT
Objectives: In this study, we analyzed the metabonomics of intermingled phlegm and blood stasis (IPBS) and its three concurrent syndromes in patients with stable angina pectoris of coronary heart disease. Methods: A total of 164 sera of separated outpatients from 12 national tradition Chinese medicine clinical research centers with IPBS or concurrent syndromes were collected for the study and assessed with LC-ESI-MS/MS (liquid chromatography-electrospray ionization tandem-mass spectrometry)-based metabolomics and multivariate statistical analysis. Results: Non-differential metabolites between IPBS and its separate syndrome combined with the top 100 most abundant metabolites in four groups were screened to reflect the essence of IPBS. Amino acid and its metabolomics and glycerol phospholipids were screened for common metabolites, and these metabolites were mainly enriched in valine, leucine, and isoleucine metabolism and glycerophospholipid metabolism. Principal component analysis revealed that the difference between IPBS and its separate concurrent syndromes was not distinct. Compared with IPBS, anserine, cytidine 5'-diphosphocholine, and 7,8-dihydro-L-biopterin separately significant increase in phlegm stasis and toxin (PST), phlegm stasis and Qi stagnation (PQS), and phlegm stasis and Qi deficiency (PQD). While these different metabolites were associated with histidine metabolism, beta-alanine metabolism, glycerophospholipid metabolism, and folate biosynthesis. Three accurate identification models were obtained to identify the difference between IPBS and its concurrent syndromes. Conclusion: Our study indicated that valine, leucine, and isoleucine metabolism and glycerophospholipid metabolism could represent the essence of IPBS; dysregulated metabolites were valuable in identifying PST from IPBS.
