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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.
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This study developed an optimal pre-processing technique for the reference substance of the classic formula Gualou Xiebai Banxia Decoction(GXBD) and established a comprehensive quality control method for GXBD reference substance to provide a reference for its overall quality evaluation. The authors prepared 15 batches of GXBD samples and innovatively used the extracted ion chromatogram under the base peak chromatogram mode to establish a liquid chromatography-mass spectrometry(LC-MS) fingerprint, identify characteristic peaks, and perform quantitative analysis of indicator components. The yield of the 15 batches of GXBD samples ranged from 50.28% to 76.20%. In the positive ion mode, 12 common characteristic peaks were detected in the LC-MS fingerprint, and the structures of five common peaks were identified by comparison with reference standards. The similarity between the fingerprint profiles of different batches of samples and the reference fingerprint profile ranged from 0.920 to 0.984. Finally, liquid chromatography-triple quadrupole mass spectrometry(LC-QQQ/MS) in multiple reaction monitoring(MRM) mode was used to determine the content of eight indicator components in GXBD, including loliolide, chrysoeriol, rutin, cucurbitacin D, macrostemonoside Ⅰ, 25S-timosaponin B Ⅱ, 25R-timosaponin B Ⅱ, and peptide proline-tryptophan-valine-proline-glycine(PWVPG). The method established in this study can reduce matrix interference in the compound, and it has good accuracy, stability, and practical value. It effectively reflects the quality attributes of GXBD samples and can be used for the comprehensive quality control of GXBD.
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Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Medicamentos de Ervas Chinesas/química , Prolina , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Aim To explore the molecular mechanism atherosclerosis by network pharmacology and in vitro of Gualou Xiebai Banxia decoction in the treatment of study.Methods All chemical constituents and targets of Gualou Xiehai Banxia decoction were retrieved from TCMSP database.OMIM, DrugBank and TTD databas¬es were searched with "atherosclerosis" as the search term , and the related targets of atherosclerosis were ob¬tained after eliminating duplicate options.DAVID da¬tabase was used for GO and KEGG pathway enrichment analysis of intersection targets.Finally, the analysis results were confirmed in the ox-LDL induced human aortic endothelial cell injury model.Results A total of 30 active compound molecules in Gualou Xiebai Banxia decoction and 78 potential targets for the treat¬ment of atherosclerosis were retrieved.The therapeutic targets were mainly related to inflammatory pathway, apoptosis and so on.(3-sitosterol was chosen as a po¬tential pharmacodynamic molecule for the treatment of atherosclerosis to verify the correctness of the results of network pharmacological analysis.In vitro experiments showed that, (3-sitosterol could prevent ox-LDL in¬duced apoptosis of human aortic endothelial cells and significantly reduce the level of IL-ip, 1L-6 and TNF- cx in cell culture medium, and protein expression of p- NF-kB/NF-kB, 1L-1 p, 1L-6 and TNF-a in cells.Conclusions The treatment effect of Gualou Xiebai Banxia decoction on atherosclerosis is mainly mediated by regulating inflammation, apoptosis and other path¬ways through multi-component effect, multiple targets and multiple pathways.
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Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China. In this study, we investigated the protective effect and underlying mechanisms GXB in type II diabetes with acute myocardial ischemia (T2DM-AMI) rats. We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells (EPCs) apoptosisviaactivating PI3K (phosphatidyl inositol 3-kinase)/Akt (serine/threonine protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling. Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of type II diabetes mellitus (T2DM) and coronary ligation to induce acute myocardial infarction (AMI). Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination. The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry. Target mRNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis. The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose, muscular enzymes, and blood lipids, and reduced oxidative stress. Furthermore, EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased mRNA and protein levels of PI3K, Akt, and eNOS compared to the controls. Conversely, T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis, combined with increased mRNA and protein levels of PI3K, Akt, and eNOS compared to those of untreated T2DM-AMI rats. Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.
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[Objective]The paper summarizes Professor HAN Xinmin's experiences on treating pediatric sigh by using Gualou Xiebai Banxia decoction.[Methods] By learning from Professor HAN Xinmin, recording the relevant cases and analyzing typical cases, to sum up the academic thoughts and effective prescription, as well as list one proved case. [Results] Professor HAN Xinmin holds that most children with sigh have syndromes of deficiency and excess. This is the case of Qi deficiency of the spleen and lung, the insufficiency of the chest Yang and with phlegm evil. Using Gualou Xiebai Banxia decoction with the method of clearing Yang Qi and removing phlegm and activating blood stasis can achieve a satisfactory clinical curative effect by treating based on syndrome differentiation. [Conclusion] Professor HAN Xinmin has unique clinical experience for treating pediatric sigh. Gualou Xiebai Banxia decoction has significant effect, which has the value of popularization and application.
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To observe the functions of Gualou Xiebai Banxia decoction（GXBD） on regulating lipid metabolism, anti-oxidation, and interposing ox-LDL/Lox-1 pathway, and to explore its anti-atherosclerosis (AS) mechanisms. AS models were established by using 42 Apo-E-/- male mice with high fat diet. AS model mice were randomly divided into the model group, simvastatin group, and GXBD high and low dose groups. C57BL/6J male mice were used as the normal control group, n=10 and the treatment lasted for 8 weeks. The levels of TC, TG, LDL-C, HDL-C, SOD, MDA, GSH-px, and ox-LDL in blood serum were tested 24 h after the last administration. The changes of aortic tissues structure were observed by HE staining; the expression levels of Lox-1 protein and the expression levels of mRNA were detected by Western blot and PCR respectively.Results showed that the blood lipid levels and MDA, ox-LDL levels in blood serum of model group were significantly higher than those in the normal control group, but SOD, GSH-px levels were significantly lower than those in the normal control group, and the Lox-1 protein and mRNA expression levels were also significantly higher than those in the control group(P<0.05), namely aortic atherosclerosis lesions were obvious in model group.The levels of blood lipid and MDA, ox-LDL of GXBD high and low dose groups and simvastatin group were significantly lower than those in model group, while SOD, GSH-px levels were significantly higher than those in model group, and Lox-1 protein and mRNA expression levels were significantly lower than those in model group(P<0.05), namely the aortic atherosclerosis lesions were significantly relieved. The above results indicated that GXBD was capable of modulating blood lipid, anti-oxidation, and inhibiting the expression of Lox-1, and interposing ox-LDL/Lox-1 pathway in the AS model Apo-E-/- mice, which may be one of the mechanisms of anti-atherosclerosis.
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Objective To observe the effect of therapies of activating blood and removing stasis, activating yang and dissipating phlegm, and warming and dredging meridians with aromatic herbs on relieving acute myocardial ischemia (AMI). Methods Rats were randomized into normal group,model group, Xuefu Zhuyu Decoction (XZD) groups (treated with XZD 20.5 and 6.8 gkg-1d-1 ), Gualou Xiebai Banxia Decoction (GXBD) groups (treated with GXBD 18.0 and 6.0gkg-1d-1 ), and Guanxin Suhexiang Capsules (GSC) groups (treated with GSC 0.19 and 0.06 gkg-1d-1 ). The AMI rat models were established by intravenous injection of pituitrin (Pit, 1.5U/kg) through the caudal vein. The effect of the three Chinese medical therapies on AMI rat electrocardiogram (ECG) and plasma endothelin (ET) level was evaluated. Results Compared with the model group, statistical significance was presented in the rise of ST segment of medication groups (P