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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.
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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.
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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.
Subject(s)
Humans , Angina Pectoris , Angina, Unstable/drug therapy , China , Drugs, Chinese Herbal , Network Meta-Analysis , Treatment OutcomeABSTRACT
The aim of this paper was to investigate whether the mechanism of salvianolic acid B in protecting H9 c2 cardiomyocytes from hypoxia/reoxygenation injury is related to the regulation of mitochondrial autophagy mediated by NIX. H9 c2 cardiomyocytes were cultured in vitro and divided into normal group, model group and salvianolic acid B group(50 μmol·L~(-1)). Hypoxia/reoxygenation injury model was established by hypoxia for 4 h and reoxygenation for 2 h. In normal group, high glucose DMEM medium was used for culture. Those in model group were cultured with DMEM medium without glucose and oxygen, and no drugs for hypoxia and reoxyge-nation. In salvianolic acid B group, salvianolic acid B prepared by glucose-free DMEM medium was added during hypoxia, and the other process was as same as the model group. The cell viability was evaluated by CCK-8 assay. The leakage of lactate dehydrogenase(LDH) was detected by microplate method. The levels of intracellular reactive oxygen species(ROS) and mitochondrial membrane potential(ΔΨm) were measured by chemical fluorescence method. The level of intracellular adenosine triphosphate(ATP) was mea-sured by fluorescein enzyme method. The autophagy related proteins LC3-Ⅰ, LC3-Ⅱ, apoptosis related protein cleaved caspase-3 and mitochondrial autophagy receptor protein NIX were detected by Western blot. As compared with the normal group, the activity of H9 c2 cardiomyocytes and ATP level were decreased(P<0.05); LDH leakage and ROS production were increased(P<0.01); ΔΨm was decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio, cleaved caspase-3 and NIX protein expression levels were increased(all P<0.05) in the model group. As compared with the model group, the activity of cells and ΔΨm were significantly increased(P<0.01); ATP level was increased(P<0.05); LDH leakage and ROS generation were decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio was decreased(P<0.01); cleaved caspase-3 and NIX expression levels were decreased(P<0.05) in the salvianolic acid B group. The protective effect of salvianolic acid B on hypoxia/reoxygenation injury of H9 c2 cardiomyocytes may be associated with inhibiting mitochondrial auto-phagy. The specific mechanism may be related to inhibiting the activation of mitochondrial autophagy mediated by NIX, increasing ΔΨm, reducing ROS production, reducing the expression of cleaved caspase-3, LC3-Ⅱ, and increasing cell viability.
Subject(s)
Humans , Apoptosis , Autophagy , Benzofurans , Cell Hypoxia , Cell Survival , Hypoxia , Myocytes, CardiacABSTRACT
Objective:To observe the effect of Shuangshen Ningxin capsule in alleviating myocardial ischemia/reperfusion injury in rats by regulating mitochondrial adenosine triphosphate（ATP）-sensitive potassium channels.Method:A total of 56 adult male Sprague-Dawley rats were randomly divided into sham-operated control group (sham), model group (model), Shuangshen Ningxin group (SSNX, 90 mg·kg-1).Shuangshen Ningxin and mitochondrial ATP-sensitive potassium channel (MitoKATP) channel inhibitor group 5-hydroxyl-acid group (SSNX+5-HD, 5 mg·kg-1), with 14 rats in each group. Except the sham operation group, the other three groups received occlusion of left anterior descending coronary artery (LAD) for 45 min, and were sacrificed 3 h after reperfusion. Myocardial ischemia and infarct size were observed by TSC Evans blue staining, and myocardial tissue damage degree was observed by hematoxylin-eosin(HE) staining. The kit was used to measure serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The ultrastructural changes of mitochondria and mitochondrial autophagy were observed under transmission electron microscope. The changes of mitochondrial membrane potential in cardiomyocytes were detected by fluorescent probe.Result:Compared with the sham group, myocardial infarct size and myocardial ischemic area percentage in the model group were significantly increased, myocardial tissue arrangement was disordered and loose, individual myocardial fibers were broken, cardiomyocytes were necrotic, and serum CK, CK-MB, LDH activities were significantly increased (P<0.01). Mitochondrial membrane potential was significantly decreased (P<0.01), and mitochondrial structure was destroyed by transmission electron microscopy. Compared with the model group, the myocardial tissue of the SSNX group was arranged orderly, and a small amount of cell edema was mildly degenerated. The percentage of myocardial infarct size and myocardial ischemic area was significantly decreased, serum CK, CK-MB, and LDH activities were significantly decreased (P<0.01), while mitochondrial membrane potential increased (P<0.01). Compared with the model group, the SSNX+5-HD group had mild myocardial tissue disorder and mild degeneration of cell edema in some areas, the percentage of myocardial infarct size and myocardial ischemic area was significantly reduced, serum CK, CK-MB, and LDH activities were significantly decreased (P<0.01), and mitochondrial membrane potential increased (P<0.01). Compared with SSNX group, SSNX+5-HD group had significant increase in serum CK, CK-MB and LDH activities (P<0.01), significant increase in the percentage of myocardial infarct size and myocardial ischemic area, and mitochondrial membrane potential Reduced (P<0.05).Conclusion:SSNX protects rat myocardial ischemia-reperfusion injury by opening mitochondrial ATP-sensitive potassium channel.
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Ischemic heart disease(IHD) is a common and frequently-occurring disease that causes serious harm to human health. Autophagy is a life process that maintains cell homeostasis by degrading macromolecules such as damaged organelles in cells. In the process of ischemic heart disease development, on the one hand, cardiomyocytes degrade macromolecules such as damaged organelles by autophagy to provide material basis for energy synthesis and maintain cell homeostasis; on the other hand, over-activated autophagy can also increase cardiomyocyte death. Ischemic heart disease has a complex pathological mechanism, and the occurrence of autophagy is closely related to the survival or death of myocardial cells, so the regulation of autophagy may be an important therapeutic target for ischemic heart disease. Traditional Chinese medicine(TCM) with obvious effects, unique advantages and great potential has been widely used in the treatment of ischemic heart disease. In recent years, more and more studies have found that TCM can protect myocardium by regulating autophagy of cardiomyocytes. In this review, we summarized recent studies on the regulation of autophagy in myocardial cells by traditional Chinese medicine in ischemic heart disease. The pharmacological mechanism of Chinese medicinein regulating autophagy to protect cardiomyocytes was reviewed through different ways(promoting or inhibiting autophagy) from three levels, i.e. active ingredient, as well as drug pair and compound. The specific mechanism of Chinese medicine in regulating autophagy to protect ischemic heart disease was explored to provide references or new ideas for clinical treatment and drug development of ischemic heart disease.