Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Effect of asiaticoside on OGD/R induced injury of H9C2 cardiomyocytes based on PI3K/Akt/Beclin-1 signaling pathway / 药学学报

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

The coronary heart disease of phlegm-stasis cementation syndrome in mini-swine based on platelet proteomics / 药学学报

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

Optimization of extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma based on network pharmacology and multi-index orthogonal test / 中国中药杂志

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.

Application and Prospect of Platelet Multi-Omics Technology in Study of Blood Stasis Syndrome / 中国结合医学杂志

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis / 中国中药杂志

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

Baicalin treats cerebral ischemia reperfusion-induced brain edema in rats by inhibiting TRPV4 and AQP4 of astrocytes / 中国中药杂志

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.

Regulatory Effect of Quyu Huatan Tongmai Prescription on Intestinal Microflora in Golden Hamster with Hyperlipidemia / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal， model， prescription， stasis-dispelling （Quyu）， phlegm-dissolving （Huatan）， and detoxification （Jiedu） groups， with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet （4 weeks）. Then hamsters in the Quyu group （1.11 g·kg-1）， Huatan group （0.39 g·kg-1）， Jiedu group （0.07 g·kg-1）， and prescription group （1.42 g·kg-1） were given （ig） corresponding drugs and those in the normal group and the model group received （ig） distilled water of equivalent volume， once a day for 6 weeks. Serum lipids were determined， and hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group， the model group demonstrated increase in body weight （P<0.05， P<0.01） and blood lipids （P<0.01）， decrease in intestinal flora diversity （P<0.05， P<0.01）， and variation of the relative abundance of intestinal flora at phylum， family， and genus levels （P<0.05， P<0.01）. Compared with the model group， Quyu Huatan Tongmai prescription controlled the body weight change， reduced the serum triglyceride （TG）， total cholesterol （TC）， and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio （LDL-C/HDL-C） （P<0.05， P<0.01）， improved the structure of intestinal flora， decreased the ratio of Firmicutes to Bacteroides （P<0.01）， raised the abundance of Bacteroidaceae， Porphyromonadaceae， Rikenellaceae， and Pasteurella （P<0.05， P<0.01）， and lowered the relative abundance of Coriobacterium （P<0.05） in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly， the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant， and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

Effect of Shuangshen Xionglian Granule on Vasodilation and PI3K/Akt/eNOS Pathway in Hyperhomocysteinemia Chronic Kidney Disease Rats / 中国实验方剂学杂志

Objective:To study the effect of Shuangshen Xionglian （SSXL） granules on vasculopathy and phosphatidylinositol 3 kinase （PI3K）/serine threonine kinase （Akt）/nitrogen oxide synthase （eNOS） signal in hyperhomocysteinemia chronic kidney disease rats. Method:Rats were randomly divided into 5 groups： sham operation group， model group， and high， medium and low-dose （8， 4， 2 g·kg-1） SSXL groups. The model of hyperhomocysteinemia chronic kidney disease in rats was established with high methionine feed combined with 5/6 nephrectomy. After 5/6 nephrectomy， continuous intragastric administration lasted for four weeks. Arterial blood pressure was measured at the 4th and 8th weeks after operation. At the end of the 8th week after the operation， blood was collected to determine serum creatinine， urea nitrogen， homocysteine （Hcy）， methionine and blood lipid. Western blot was used to detect the expressions of PI3K/Akt/eNOS pathway-related proteins， such as p-p85， p-Akt and p-Ser177 in thoracic aorta， and serum NO and eNOS were measured. The changes of endothelium-dependent relaxation and non-endothelium-dependent relaxation were measured by the method of isolated thoracic aorta ring. Pathological htoxylin eosin （HE） staining was used to observe the changes of renal tissue and thoracic aorta. Result:At the 8th week of the experiment， compared with the sham operation group， arterial systolic blood pressure， serum urea nitrogen， creatinine， Hcy， methionine， total cholesterol and low-density lipoprotein of the model group were significantly increased. Four weeks later after administration， arterial systolic blood pressure， serum urea nitrogen， Hcy， methionine， serum total cholesterol and serum low-density lipoprotein were significantly reduced in each dose group （P<0.05， P<0.01）. The creatinine in the SSXL 8， 4 g·kg-1 group was significantly reduced （P<0.05）. The nitric oxide content of SSXL in each dose groups were increased compared with that in the model group （P<0.05， P<0.01）， and the serum eNOS activity of the SSXL in the SSXL 8 g·kg-1 group was significantly increased compared with that in the model group （P<0.05）. The endothelium dependent and non-endothelium dependent vasodilation of thoracic aortic rings in the model group were significantly damaged. The cumulative concentration of acetylcholine （1×10-5.5~1×10-4 mmo1·L-1） in the SSXL 8 g·kg-1 group was significantly improved （P<0.05， P<0.01）. The diastolic degree of the vascular ring in the SSXL 8 g·kg-1 group was significantly higher than that in the model group （P<0.05）. Western blot results showed that the expressions of p-85， p-Akt and p-Ser177 in blood vessels increased in the sham group compared with those in the model group （P<0.01）. Compared with the model group， the phosphorylation level of this pathway was increased in the SSXL groups， and the expressions of p-Akt and p-Ser177 in the SSXL 8 g·kg-1 group were significantly increased （P<0.05）. The pathological results showed that the pathological changes of thoracic aorta and renal tissue in the dosages of SSXL were significantly reduced compared with those in the model group. Conclusion:SSXL granules can improve hyperhomocysteine and dyslipidemia in rats of chronic kidney disease with hyperhomocysteine， reduce serum creatinine， urea nitrogen levels and arterial systolic blood pressure， and improve vascular morphology and diastolic function， which may be related to the regulation of the PI3K/Akt/eNOS signaling pathway.

Mechanism of 'Invigorating Qi and Promoting Blood Circulation' Drug Pair Ginseng-Danshen on Treatment of Ischemic Heart Disease Based on Network Pharmacology / 中国结合医学杂志

OBJECTIVE@#Using network pharmacology to explore the mechanism of the 'invigorating qi and promoting blood circulation' drug pair Ginseng-Danshen (Salvia miltiorrhiza) on treatment of ischemic heart disease (IHD).@*METHODS@#The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential targets of the pair were identified. The pharmacodynamics of the pair was analyzed using network pharmacology. The targets of IHD were identified by database screening. Using protein-protein interaction network, the interaction targets of Ginseng-Danshen on IHD were constructed. A "constituent-target-disease" interaction network was constructed using Cytoscape software, Gene Ontology (GO) term enrichment analysis and biological pathway enrichment analysis were carried out, and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.@*RESULTS@#Seventeen active constituents and 53 targets were identified from ginseng, 53 active constituents and 61 targets were identified from Danshen, and 32 protein targets were shared by ginseng and Danshen. Twenty GO terms were analyzed, including cytokine receptor binding, cytokine activity, heme binding, and antioxidant activity. Sixty Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were analyzed, including phosphatidylinositol 3-kinase-serine-threonine kinase (PI3K-AKT) signaling pathway, p53 signaling pathway, interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, and the advanced glycation end product (AGE)-the receptor for AGE (RAGE) signaling pathway in diabetic complications.@*CONCLUSION@#The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody, inhibiting the production of peroxides, removing the endogenous oxygen free radicals, regulating the expression of inflammatory factors, reducing myocardial cell apoptosis and promoting vascular regeneration.

Application prospects of single-cell transcriptome sequencing in traditional Chinese medicine research / 中国中药杂志

Single-cell transcriptome sequencing(scRNA-seq) can be used to analyze the expression characteristics of the transcriptome at the level of individual cell, and discover the heterogeneity of gene expression in individual cell that is "diluted" or averaged in study of group organization. The scRNA-seq, with the characteristics of standardization, high-throughput, and high integration, can greatly simplify the experimental operation and significantly reduce the consumption of reagents. At the same time, a variety of cells are screened and the gene expression patterns are analyzed at the single-cell level to provide a more efficient detection technique and more rich and accurate information for drug research. In the field of traditional Chinese medicine(TCM), the scRNA-seq is still a new technology, but the individual and precision concepts embodied by scRNA-seq and the theory of TCM syndrome differentiation and treatment have reached the same effect between the micro and macro aspects. This study tried to broaden the thinking for the modernization of TCM by introducing the development of scRNA-seq technology and its application in modern drug research and discussing the application prospects of scRNA-seq in TCM research.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction / 中国药理学与毒理学杂志

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. METHODS The patients with coronary heart dis?ease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months, and the changes of cardiac function were observed. 61 serum samples (including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group) were analyzed by non labeled proteomics. The disease group was used as the control group, and the protein with expression level difference of more than 1.2 folds (P<0.05) was screened. The molecular function, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction, regulate blood glucose and blood lipid levels, prolong thrombin time, and improve heart function. The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group. Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1, alpha-2 and other proteins to act on HDL assembly, platelet degradation, PI3K Akt signaling pathway, and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome. CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syn?drome of coronary heart disease. It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins. This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Effect of Yinxing Mihuan Oral Solutionon P2RX7/NLRP3 Signaling Pathway in Depression Model Rats Induced by Isolation Combined with Chronic Unpredictable Mild Stress / 中国实验方剂学杂志

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution （YMO） by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress （CUMS） and then randomly divided into model group， fluoxetine group （10 mg·kg^-1） and high-dose （618 mg·kg^-1） and low-dose （309 mg·kg^-1） YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days， and rats were administered the 8th day after stimulation at a dose of 10 mL·kg^-1 for 14 days， except those in the blank control and model groups which were given distilled water. Afterward， the sucrose preference test， open field test， tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin （HE） staining. The content of interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， interleukin-6 （IL-6） and tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） in the hippocampus of rats in each group and the expression of NOD-like receptor 3 （NLRP3） and other proteins in its related activation signaling pathways were detected with multi-factor detection （Luminex） and Western blot. Result:After 14 days of continuous administration， compared with the blank control group， the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the fluoxetine group and the high-dose YMO group saw increases in the times of rearing， times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension （<italic>P</italic><0.05， <italic>P</italic><0.01）. The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened， without obvious microglia infiltration observed. The levels of IL-1<italic>β</italic>， IL-6 and TNF-<italic>α</italic> in the hippocampus of the model group increased significantly as compared with the blank control group （<italic>P</italic><0.05， <italic>P</italic><0.01）， and their content in the high-dose YMO group was significantly lowered in the comparison with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Molecular biology experiments demonstrated that compared with the results of blank group， the expression of purinergic receptor P2X7 （P2RX7）， NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1 and IL-1<italic>β</italic> remarkably increased in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Additionally， the expression of P2RX7， NLRP3， ASC， Caspase-1 and IL-1<italic>β </italic>was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS， and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

Mechanism of Astragali Radix Vesicle-like Nanoparticles for Reducing Blood Glucose in db/db Diabetic Mice by Regulating Gut Microbiota / 中国实验方剂学杂志

Objective:To study the extraction method and characteristics of vesicle-like nanoparticles （VLNs） in Astragali Radix decoction， and to explore the mechanism of the VLNs in reducing blood glucose by regulating the gut microbiota of db/db diabetic mice. Method:Ultracentrifugation and size exclusion chromatography were used to enrich VLNs from Astragali Radix decoction， and the morphology， particle size and concentration of the VLNs were analyzed by transmission electron microscope and nanoparticle tracking analyzer. The db/db diabetic mice were randomly divided into model group， Astragali Radix VLNs high-， medium- and low-dose （21.1， 10.6， 5.3 g·kg^-1） groups and metformin group （0.25 g·kg^-1） according to their blood glucose levels. There were 7 mice in each group， and another 7 C57BL/6 mice were set as the normal group. The mice were given intragastrically for 3 weeks （once a day）， and the changes of fasting blood glucose were observed every week. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of liver and pancreas of diabetic mice. The feces of mice were collected for 16S rRNA diversity detection of intestinal microbes. Result:The size of the nanoparticles obtained by the two methods was about 200 nm. Astragali Radix VLNs extracted by ultracentrifugation had a typical saucer-like shape with the concentration of 3.0×10¹¹ particles·mL^-1. The morphology of Astragali Radix VLNs obtained by size exclusion chromatography was relatively poor with the concentration of 2.2×10¹¹ particles·mL^-1. After 3 weeks of administration， compared with the model group， Astragali Radix VLNs high-， medium- and low-dose groups could significantly reduce the fasting blood glucose of diabetic mice （<italic>P</italic><0.05， <italic>P</italic><0.01）. The VLNs could improve the gut microbiota dysbiosis， significantly decrease the ratio of Firmicutes/Bacteroidota， and increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. Conclusion:Astragali Radix VLNs may reduce the blood glucose of db/db diabetic mice by adjusting the ratio of Firmicutes/Bacteroidota in the intestinal flora.

Molecular Mechanism Analysis of Jiangtang Xiaozhi Tablets in Treatment of NAFLD / 中国实验方剂学杂志

Objective:To explore the molecular mechanism of Jiangtang Xiaozhi tablets （JTXZT） in the treatment of non-alcoholic fatty liver disease （NAFLD） by means of network pharmacology and molecular docking. Method:With the help of traditional Chinese medicine （TCM） Systems Pharmacology Database and Analysis Platform （TCMSP）， TCMs Integrated Database （TCMID）， Encyclopedia of TCM （ETCM） and Bioinformatics Analysis Tool for Molecular Mechanism of TCM （BATMAN-TCM）， the chemical compositions of medicinal materials in JTXZT were obtained， the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database （GeneCards）， Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD） and DisGeNET， and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database， the protein-protein interaction （PPI） network of therapeutic targets was constructed， and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally， the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking. Result:The key components of JTXZT for treatment of NAFLD were quercetin， luteolin， kaempferol， berberine， isorhamnetin， betulinic acid， oleanolic acid， ursolic acid. formononetin and hexitol， and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 （MAPK1）， Jun proto-oncogene， activator protein-1 （AP-1） transcription factor subunit （JUN）， MAPK3， protein kinase B1 （AKT1 or Akt1）， tumor protein p53 （TP53）， E1A binding protein p300 （EP300）， Fos proto-oncogene， AP-1 transcription factor subunit （FOS）， tumor necrosis factor （TNF），amyloid beta precursor protein （APP） and cytochrome P450 family 2 subfamily E member 1 （CYP2E1）. Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process， oxidation-reduction process， cholesterol metabolic process and other biological processes， regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， MAPK signaling pathway， NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD. Conclusion:JTXZT treats NAFLD through multiple active components， multiple key targets and multiple action pathways.

Analysis of Chinese Patent Medicines in 2020 Edition of Chinese Pharmacopoeia (Part Ⅰ) for Cough of Children / 中国实验方剂学杂志

Objective:To analyze the functions and indications， formulation， dosage form and medication characteristics of Chinese patent medicines in the 2020 edition of<italic> Chinese Pharmacopoeia</italic> （part Ⅰ） for treating cough of children， and to provide ideas for the clinical rational application and provide reference for the research and development of new cough medicines for children. Method:The name， dosage form， formulation， functions and indications， usage and dosage， and other information of Chinese patent medicines for cough were collected from the 2020 edition of <italic>Chinese Pharmacopoeia </italic>（part Ⅰ）， then relevant information was input into Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0， and data analysis and mining were carried out through the analysis module of prescription medication rule， VOSviewer 1.6.14 was used to make drug clustering network view of Chinese patent medicines for the treatment of exogenous wind cold， exogenous wind heat and phlegm heat cough. Result:In the 2020 edition of <italic>Chinese Pharmacopoeia </italic>（part Ⅰ）， a total of 75 kinds of Chinese patent medicines for treating cough of children were collected， including 34 kinds of Chinese patent medicines for adults and children， 41 kinds of Chinese patent medicines for children only. There were 7 types of traditional Chinese medicine syndromes， such as wind-cold attacking the lung， wind-heat invading the lung and phlegm-heat obstructing the lung. There were 45 Chinese patent medicines for treating exogenous cough， accounting for 60%， among which 35 kinds were used for exogenous wind-heat cough and 10 kinds were used for wind-cold cough. There were 30 kinds of Chinese patent medicines for treating internal injury cough， including 19 kinds of medicines for phlegm heat obstructing the lung， 4 kinds of medicines for phlegm dampness containing the lung and phlegm food stagnation， 2 kinds of medicines for Yin-deficiency lung heat， 1 kind of medicine for the lung and spleen Qi-deficiency. The formulation analysis showed that Glycyrrhizae Radix et Rhizoma， Platycodonis Radix， Scutellariae Radix， Armeniacae Semen Amarum and Citri Reticulatae Pericarpium appeared frequently， which were mainly cold， bitter and sweet herbs， mainly belonged to the lung and stomach meridians. According to the analysis of administration and dosage forms， 71 kinds of Chinese patent medicines were administered through gastrointestinal tract， including 20 kinds of granules， 15 kinds of oral liquids， others included syrups， pills， capsules， tablets， powers， etc. Only 2 suppositories and 2 injections were administered by nongastrointestinal tract. The usage and dosage of most Chinese patent medicines were not clear. Conclusion:In the 2020 edition of <italic>Chinese Pharmacopoeia </italic>（part Ⅰ）， the main syndromes of Chinese patent medicines for cough of children are exogenous wind-heat and phlegm-heat obstruction in the lung. Most of the Chinese medicines are cold， bitter and sweet， and their meridians are mainly lung and stomach meridians. Scutellariae Radix， Lonicerae Japonicae Flos and Forsythiae Fructus are the most common medicines of exogenous wind heat syndrome. Perillae Folium， Citri Reticulatae Pericarpium and Ephedrae Herba are the most common medicines of exogenous wind cold syndrome. Meanwhile， Scutellariae Radix， Platycodonis Radix and Armeniacae Semen Amarum are the most common medicines of phlegm heat obstructing the lung syndrome. At present， the dosage forms of Chinese patent medicines used for treating cough of children are too few and the dosage labeling is not comprehensive， so it is necessary to further strengthen the research and development of new Chinese medicines suitable for characteristics of children.

Effect of Shuangshen Ningxin Capsules on Cardiac Function and Hemodynamics in Rats with Coronary Microvascular Dysfunction / 中国实验方剂学杂志

Objective:To investigate the effect of Shuangshen Ningxin capsules （SSNX） on cardiac hemodynamics and cardiac function in rats with coronary microvascular dysfunction. Method:Rats were randomly divided into a sham operation group， a model group， a nicorandil group （5 mg·kg^-1）， and high- （180 mg·kg^-1）， medium- （90 mg·kg^-1）， and low-dose （45 mg·kg^-1） SSNX groups. Rats received corresponding drugs for 7 days. Two hours after the last administration， the model of coronary microvascular dysfunction was induced by left ventricular injection of embolic microspheres （40-120 μm， about 1 000 microspheres）. Twenty-four hours after modeling， left ventricular internal dimension in diastole （LVIDd）， left ventricular internal dimension in systole （LVIDs） left ventricular end-diastolic volume （LVEDV）， left ventricular end-systolic volume （LVESV）， stroke volume （SV）， cardiac output （CO）， left ventricular ejection fraction （EF）， and left ventricular shortening rate （FS） were detected by echocardiography. Cardiac catheterization was used to observe the arterial systolic blood pressure （SBP）， diastolic blood pressure （DBP）， left ventricular systolic pressure （LVSP）， left ventricular end-diastolic pressure （LVEDP）， maximum rate of increase in left ventricular pressure （LV+dp/dt_max）， and maximum rate of decrease in left ventricular pressure （LV-dp/dt_max）， and the mean arterial pressure （MAP） was calculated. Heart rate （HR） was calculated according to Ⅱ lead ECG. Biochemical analysis was carried out to detect the activities of creatine kinase （CK）， creatine kinase-MB （CK-MB）， and lactate dehydrogenase （LDH）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum cardiac troponin T （cTnT）. Western blot was used to detect the protein expression of Caspase-3， Bcl-2， and Bax， and 2，3，5-triphenyltetrazolium chloride （TTC） staining to observe the area of myocardial infarction. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of the myocardium. Result:As revealed by echocardiography， compared with the sham operation group， the model group showed reduced SV， CO， EF， and FS （<italic>P</italic><0.01）， and increased LVIDs and LVEDV （<italic>P</italic><0.01）. Compared with the model group， the SSNX groups showed increased EF （<italic>P</italic><0.05， <italic>P</italic><0.01） and FS （<italic>P</italic><0.01）， and the high- and medium-dose SSNX groups displayed reduced LVIDs and LVESV， and increased LVEDV， SV， and CO （<italic>P</italic><0.05， <italic>P</italic><0.01）. SBP， DBP， MAP， LVSP， LV+dp/dt_max， and LV-dp/dt_max in the model group were lower than those in the sham operation group （<italic>P</italic><0.01）， while there was no significant difference in HR. SSNX improved hemodynamics of rats， and increased SBP， DBP， MAP， LVSP， LV+dp/dt_max， LV-dp/dt_max， and HR as compared with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. The serum CK， LDH， CK-MB， and cTnT levels in the model group were higher than those in the sham operation group （<italic>P</italic><0.01）. Compared with the model group， SSNX groups reduced serum CK， LDH， CK-MB， and cTnT （<italic>P</italic><0.05，<italic> P</italic><0.01）. Compared with the sham operation group， the model group displayed increased expression of Caspase-3 protein in the myocardium （<italic>P</italic><0.01） and reduced expression of Bcl-2 protein （<italic>P</italic><0.05）. The expression of Caspase-3 protein in the myocardium of SSNX groups was lower than that in the model group， and statistical difference was observed between the low-dose SSNX group and the model group （<italic>P</italic><0.05）. Compared with the model group， the SSNX groups exhibited increased expression of Bcl-2 in the rat myocardium， and the statistical difference was observed in the high-dose SSNX group <italic>（P</italic><0.01）. As demonstrated by the TTC staining， compared with the model group， SSNX groups showed reduced areas of myocardial infarction （<italic>P</italic><0.01）. The HE staining indicated that the pathological injury in myocardial tissues of the SSNX groups was relieved as compared with that in the model group. Conclusion:SSNX can significantly enhance the cardiac function after coronary microvascular dysfunction caused by embolic microspheres， improve cardiac hemodynamics， reduce the area of myocardial infarction， and decrease CK， LDH， CK-MB， and cTnT levels. The mechanism may be related to the inhibition of cardiomyocyte apoptosis to protect the myocardium.

Network Meta-analysis of clinical efficacy of Chinese herbal injection in adjuvant treatment of unstable angina pectoris / 中国中药杂志

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.

Research progress on Chinese medicinal material-derived active polypeptides against ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ischemic cardiovascular and cerebrovascular diseases threatening human health and survival have high morbidity and mortality. The common cause of them is reduced blood supply caused by vascular stenosis, atherosclerosis, and infarction. However,the pathological processes of ischemic cardiovascular and cerebrovascular diseases are complex, involving oxidative stress, calcium overload, inflammation, apoptosis, autophagy and other mechanisms. Protein drugs such as recombinant tissue plasminogen activator(rt-PA) and urokinase have been proved with excellent therapeutic effects and huge economic and social benefits in the clinical treatment and interventional therapy. Among them, peptide drugs have shown unique advantages and potential prospects owing to their strong biological activity, high target specificity, biochemical diversity, and low toxicity. Chinese medicinal materials, characterized by multi-component and multi-target therapy, have also shown excellent clinical efficacy against ischemic cardiovascular and cerebrovascular diseases. However, the research and development of related peptides in Chinese medicinal materials is at the initial stage. Therefore, this paper reviewed the targets and action mechanisms of a variety of Chinese medicinal material-derived polypeptides with activities against ischemic cardiovascular and cerebrovascular diseases, aiming to provide support for the in-depth research as well as the clinical development and application of these polypeptides.