[Exploration on mechanisms of Xiaoyao Powder in treating atherosclerosis and depressive disorder with concept of "treating different diseases with same method" based on network pharmacology].

The aim of this paper was to explore the mechanism of Xiaoyao Powder in treating atherosclerosis and depressive disorder with concept of "treating different diseases with same method" based on network pharmacology. TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and SymMap databases were used to search all the chemical components and targets related to Xiaoyao Powder. After preliminary screening, the network of "herbs-compounds-targets" was constructed. Through DisGeNET, CTD(Comparative Toxicogenomics Database) and TTD(Therapeutic Target Database), the targets of atherosclerosis and depressive disorder were obtained. The common targets were obtained by intersecting the herbal targets and disease targets. In order to screen the key common targets, STRING and Cytoscape were used to analyze the protein-protein interaction of common targets. BioGPS was used to obtain their distribution information in organs and tissues. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) analysis were conducted through Metascape. About 1 355 compounds of Xiaoyao Powder were found by TCMSP and Symmap database; 161 active compounds were screened out according to standard of oral bioavailability≥30% and drug like index≥0.18; 274 herbal targets were obtained and the "herbs-compounds-targets" network was constructed. About 1 004 atherosclerosis targets and 578 depressive disorder targets were obtained, and 37 common targets were obtained after intersection with herbal targets. By using STRING and Cytoscape for protein-protein interaction analysis, 18 key targets were screened. BioGPS showed that the key common targets were mainly distributed in heart, amygdala, pineal, liver and smooth muscle. Metascape was used for GO enrichment analysis and the results showed that there were 929 biological processes, 25 cell components and 23 molecular functions. Enrichment ana-lysis of KEGG showed that there were 108 signal pathways such as AGE-RAGE, HIF-1, FoxO, Th17 cell differentiation and IL-17 signal pathways, which were mainly related to neuroendocrine system, metabolism, immune inflammation and oxidative stress. In conclusion, the main mechanism of Xiaoyao Powder in treating atherosclerosis and depressive disorder with concept of "treating different diseases with same method" was related to neuroendocrine system, metabolism, immune inflammation and oxidative stress-related signal pathway, providing reference for further experimental verification, potential pharmacological mechanism and clinical application.

Meta-analysis of Zhibitai Capsules combined with statin in reducing blood lipid levels in patients with coronary heart disease / 中国中药杂志

To systematically review the efficacy and safety of Zhibitai Capsules combined with chemical drugs versus chemical drugs alone in regulating blood lipid of patients of coronary heart disease, so as to provide evidence-based reference for clinical treatment. In this study, PubMed, EMbase, Cochrane Library, China Knowledge Network Database(CNKI), Technology Journal Database(VIP) and WanFang Database(WanFang) were retrieved to find the randomized controlled trials(RCT) about therapeutic efficacy of Zhibitai Capsules combined with statins(experimental group)versus statins alone(control group)in the treatment of regulating blood lipid of patients with coronary heart disease. The retrieval time was restricted to be from the inception to October 2019. The data were extracted from the randomized controlled trials. Meta-analysis was conducted by RevMan 5.3 statistical software after quality evaluation by Cochrane 5.1.0 quality evaluation tool(blood lipid level, inflammation indicators, traditional Chinese medicine syndrome score and adverse reactions). A total of 11 RCT were included, involving 1 538 patients. The results of Meta-analysis showed that in terms of decrease of total cholesterol(MD=-0.15,95%CI[-0.25,-0.05],P=0.004), decrease of triglycerides improvement(MD=-0.16,95%CI[-0.23,-0.10],P<0.000 01), decrease of low-density lipoprotein(MD=-0.08,95%CI[-0.15,-0.01],P=0.03), and increase of high-density lipoprotein(MD=0.06,95%CI[0.03,0.10],P=0.000 2), experimental group was better than control group. At the same time, the incidence of adverse reactions were low in the experimental group(OR=0.40,95%CI[0.18,0.85],P=0.02). As a result, in treatment of coronary heart disease, the therapeutic efficacy of Zhibitai Capsules combined with statins is better than statins alone in lowering total cholesterol level, triglyceride level, low-density lipoprotein level, and increasing high-density lipoprotein level. Patients in the experimental group had a low incidence of adverse events, but the heterogeneity was slightly higher, and the result had a poor stability. However, due to the small sample size of studies included, some experimental designs were not perfect, which reduces the recommendation level and evidence intensity of this system evaluation. Therefore, high-quality multi-center, large-sample, randomized, double-blind randomized controlled trials are needed for providing more reliable basis.

Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway / 中国结合医学杂志

OBJECTIVE@#To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by Pollen Typhae total flavone (PTF).@*METHODS@#Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), a shRNA group (transducted with PERK shRNA lentiviral particles), a scramble shRNA group (transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability, and the level of apoptosis was monitored by flow cytometry.@*RESULTS@#The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and shRNA groups. Moreover, the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK, eIF2α, ATF4 and CHOP, which were attenuated in PTF treatment groups and shRNA groups.@*CONCLUSIONS@#The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway, which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.