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Objective: To explore the molecular mechanism of Taoren-Honghua herb pair (THP) on syndrome of bloodstasis based on the network pharmacology. Methods: We collected THP's compounds from traditional Chinese Medicinedatabases and input them into Pharm Mapper to get their potential targets, and collected the known targets of compoundsby Scifinder. Then we did KEGG-pathway analysis by DAVID database. Finally draw and analyze the network byCytoscape by information above. Results: Seventeen compounds of THP acquired 74 known targets, which was associatedwith four modules: improving the hemodynamics, anticoagulation, anti-inflammation, regulating apoptosis andproliferation. We also got 317 potential targets through PharmMapper and got 128 signaling pathway through pathwayenrichment including 39 disease-related pathways, 25 endocrine-related pathways, 11 immune-related pathways and soon. Conclusion: The four modules of the known target are exactly related to the four characteristics of the syndrome ofblood stasis. The potential targets and the 128 signal pathways involve a variety of pathophysiological processes of thesyndrome of blood stasis. These reflect the molecular mechanism of THP intervention in the syndrome of blood stasis
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Intracerebral Hemorrhage (ICH) is a common cerebrovascular disease with high disability rate and high mortality rate.A large number of clinical and experimental studies have shown that the abnormal metabolism of iron in the brain tissue around the hematoma after ICH is an important cause of secondary brain damage such as brain edema and neuronal apoptosis.It is an important factor affecting the outcome of patients.This article reviews the abnormal metabolism of iron and its significance after ICH.
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Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.
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Objective: To establish a method for determining the content of dracorhodin as an indicator in the quality control with methodological studies to provide basis for the preparation process study of Qilisan gel. Methods: An HPLC method was used with a DiamonsilR C18 (250 mm ×4. 6 mm, 5 μm) column, the detection wavelength was set at 440 nm and the column temperature was 30 ℃. Acetonitrile-0. 05 mol·L-1 sodium dihydrogen phosphate solution (45 ∶ 55) was used as the mobile phase, and the flow rate was l. 0 ml·min-1 . Results: The content of dracorhodin was in a good linear relationship (r =0. 999 6) within the range of 1. 632-64. 250 μg·ml-1 , and the average recovery was 99. 02%(RSD =0. 77%, n =6). The number of theoretical plates was calculated as 7 100 according to the dracorhodin perchlorate peak without any interference from the negative sample. Conclusion: The method is objective, accurate and sensitive with high reliability, easy operation and fast process. The measurement results can be used as the quality control basis for the preparation process study of Qilisan gel.
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This systematic review was aimed to evaluation the effectiveness and safety of supplementingqi and activating blood circulation prescriptions in the treatment of cerebral ischemic stroke. Dtabases both at home and abroad were electronically searched for randomized controlled trials (RCTs) on supplementingqi and activating blood circulation prescriptions in the treatment of cerebral ischemic stroke. And meta-analyses were performed using RevMan 5.0 software. The results showed that 27 studies were included, which contained 2 908 cases. There were 1 490 cases in the treatment group, and 1 418 cases in the control group. The results of meta-analyses indicated that supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had significant differences in the effective rate for cerebral ischemic stroke compared with the single using of routine treatment of modern medicine with significant difference (OR = 5.39, 95%CI (4.03, 7.22),P < 0.000 01). The treatment of supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had better treatment effect on neurological function defects for cerebral ischemic stroke compared with the single using of routine treatment of modern medicine with significant difference (WMD = -2.99, 95%CI (-3.26, -2.72),P < 0.000 01). In addition, the treatment of supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had better treatment effect on improving the activity of daily living (WMD = 9.65, 95%CI (8.36, 10.93),P < 0.000 01). Adverse reaction and event was mild in 2 included research reports. It was concluded that the treatment of supplementingqi and activating blood circulation prescription or it combined with routine treatment in modern medicine was quite effective in the treatment of cerebral ischemic stroke by the existed limited evidences. It can also improve the nerve dysfunction and the ability of daily living. Due to the limited quantity of the included studies and the evidence with limited strength, further high-quality RCTs were needed to verify the forementioned conclusion.
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Objective To observe the regularities of distribution of TCM syndrome types and correlation between TCM syndrome types and cardiovascular prognosis risk factors of elderly hypertensive patients in three different urban and rural communities.Methods Totally 299 elderly hypertensive patients who conformed to the hypertensive diagnostic criteria from 896 respondents which participated in the health monitoring questionnaire drafted by health management team of China Academy of Chinese Medical Sciences were screened. The syndrome types were differentiated according to Guiding Principle of Clinical Research on New Drugs of Traditional Chinese Medicine (for Trial Implementation). The levels of some risk indicators, such as blood glucose, blood lipid, CREA, ET, Hcy and mALB were measured by radioimmunoassay, enzymatic cycling assay and other methods. Age, gender, BMI and pulse pressure were recorded.Results The TCM syndrome types of 299 elderly hypertensive patients were deficiency of yin and yang type (74 cases), hyperactivity of yang due to yin deficiency type (65 cases), blood stasis syndrome type (62 cases), stagnation of phlegm-dampness type (61 cases), hyperactivity of liver-fire type (37 cases). Single factor analysis showed that there existed statistical significance among BMI, FBG, GHbA1c, CREA, TC, LDL-C, ET, Hcy and mALB in the 5 TCM syndromes (P<0.05,P<0.01), and the statistical significance was more apparent in the stagnation of phlegm-dampness type, blood stasis syndrome type and hyperactivity of yang due to yin deficiency type. Discriminant analysis showed BMI and Hcy have certain reference value for the diagnosis of TCM syndrome types in elderly hypertensive patients. Binary-Logistic regression analysis showed that the course of disease had a positive correlation with syndrome of deficiency of yin and yang.Conclusion Compared with other types of elderly hepertensive patients, stagnation of phlegm-dampness type and blood stasis syndrome type are more closely related to hypertension cardiovascular prognosis risk factors.
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Objective To observe effects of Naotaifang on MMP-9, NF-κB and TIMP-1 after focal cerebral ischemia in rats. Methods The rats were randomly divided into sham operation group, model group, and Naotaifang low- (3 g/kg), medium- (9 g/kg), high- dose (27 g/kg) group. After 3 days of corresponding therapy by intragastric administration once a day, the regional cerebral ischemia model was made by middle cerebral artery occlusion (MCAO) with suture method. Following 3 days, the rats were treated with previous method. On the third day, hippocampal C2 region of ischemic tissue was detected by HE dyeing. And the contents of MMP-9, NF-κB and TIMP1 proteins in hippocampal C2 region were measured by immunohistochemical method. Results The number of normal brain cells in high dose group of Naotaifang was more than that of the model group, and only a few cells appeared nucleus pycnosis. The MMP-9 expression of all dose groups of Naotaifang were significantly decreased than model group (P<0.05). The NF-κB expression of high and medium dose groups of Naotaifang were significantly decreased (P<0.05). The TIMP1 expression of all dose groups of Naotaifang were significantly increased compared with sham operation group (P<0.05). Conclusion The mechanism of Naotaifang protecting blood brain barrier against injury of cerebral ischemia may be involved in ameliorating MMP, NF-κB and increasing TIMP1 expression.
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Through comparative study on Naotaifang containing serum and plasma proteomics (peptide), this article revealed differential proteins (peptides) in the Naotaifang. The characteristics of differential proteins were identified with mass spectrometry. It provides scientific evidences for the pharmacodynamic material basis and Chinese herbal medicine plasma pharmacological method development in the exploration of Naotaifang. A total of 20 healthy adult SD rats were randomly divided into the control group, Naotaifang treatment group according to their weights. Ten rats in each group. Intragastric administration of medication was given for seven consecutive days. Before surgery, rats were fed with water but without food. One hour after the last drug administration, 10% chloral hydrate was injected for intraperitoneal anesthesia. Blood was taken through the common carotid artery. Serum and plasma samples were made after blood was taken from each rat. Serum and plasma samples of five rats were randomly selected from each group. And the two-dimensional electrophoresis (2-DE) technique was used in the comparative study of serum pro-teomics (peptide). The 300 DPI scanning and PDQuest 7.3.0 were used in the analysis. The ESI-MS/MS was used to identify important differences in proteins and screen characteristic serum and plasma protein. The results showed that 20 differential proteins of 5 plasma samples were identified. There were 15 types of proteins expressing up-regulation and 5 types expressing down-regulation. Comparative analysis on the 2-DE gel pictures of Naotaifang containing serum, 19 differential proteins of 5 plasma samples were identified, among which 15 types of proteins express up-regulation and 4 down-regulation. Comparative analysis on the 2-DE gel pictures of Naotaifang containing serum and Naotaifang containing plasma showed that 24 differential proteins of 5 plasma samples were identified, among which 9 types of proteins express up-regulation and 15 down-regulation. The highly expressed proteins were selected to MALDI-TOF-MS between Naotaifang containing serum and Naotaifang containing plasma. There were six successful-ly identified proteins, which were inter-alpha trypsin inhibitor, heavy chain 3, group-specific component, comple-ment factor B, Receptor Complexed with A Heterodimeric Fc, isoform CRA-d, Transferrin. It was concluded that protein with obvious changes in the Naotaifang containing serum and plasma may be related with fibrinolysis and an-ticoagulant. These proteins are involved in angiogenesis, inflammation and other pathological regulations of physiolog-ical processes. They are of great significance in the study of effective target and its signal transduction pathway of Naotaifang.
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Objective To summarize the published studies of diabetic cerebral infarction treated by integration of traditional and western medicine (ITWM) or pure western medicine and compare their clinical curative effects. Method The clinical study of ITWM for diabetic cerebral infarction were collected and seleted according to the standard. The effect of ITWM and only western medicine was compared, and Meta-analysis was made. Result 59 studies were included to analysis neurological deficit and the total efficiency. Meta-analysis revealed that the improvement of ITWM is better than pure western medicine treatment. Conclusion The existed limited evidences suggest that ITWM treatment of diabetic cerebral infarction can significantly improve neurological deficit and curative effect. More high-quality randomized, double-blind, placebo-controlled trials are needed to confirm the efficacy and safety of ITWM treatment of diabetic cerebral infarction.
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Objective:To approach the effect of Naotangfang extracts on expression of vascular endothelial growth factor(VEGF) after focal cerebral infarct in rats. Methods:30 Sprague-Dawley(SD) rats were randomly divided into 6 groups:sham operation group,model group,Naotaifang extract groups(low,middle,and high dosage) ,and Naofukang group. Some indexes were detected such as neurological scores,VEGF mRNA expression by RT-PCR,and the number of VEGF positive cells by immunohistochemical methods. Results:The symptoms in nervous function were improved in the Admin. groups,especially in the Naotaifang middle dosage group. The number of VEGF positive cells and VEGF PCR production in Naotaifng middle dosage group was higher than that in the model group. Conclusion:Naotaifang has neuroprotective effect against focal cerebral ischemic injury by improving the expression of VEGF.
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Objective To explore the delayed protection of ischemic preconditioning against myocardial ischemia-reperfusion injury in rabbits. Methods Twenty four healthy rabbits were randomly into sham, ischemia-reperfusion(I/R) and ischemic preconditioning(IP) groups, each group containing 8 rabbits. After 24h IP, rabbits in IP group received 60 min coronary artery occlusion followed by 120 min reperfusion. Myocardial morphological changes were observed by optics microscope and electron microscope, infarction size and the area at risk were determined by triphenyltetrazolium chloride(TTC) and Evan's blue dye, and concentrations of adenosine and calcitonin gene-related peptide(CGRP) in serum were assayed. Results There were a few of cardial fibers ruptured, focus hemorrhage and a mass of inflammatory cell infiltration, and the concentrations of adenosine and CGRP in serum also decreased in rabbits of I/R group. Above changes were improved in rabbits of IP group, and infarction size and the area at risk markedly reduced compared with sham group and I/R group(P
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The main reasons to doubt the validity of serum pharmacology include:①The components of medical herbs absorbed from gastrointetinal tract enter circulating plasma,not serum in vivo.②Blood coagulation involves the activation of a series of proenzymes,and the proteases induce leukocytes to release lysosomal enzymes.These enzymes may degrade some herbal components.③Thrombin can stimulate platelets and leukocytes to secrete many biologically active substances.④Fibrinolysis,complement and kinin systems are activated during blood coagulation.⑤The processes of serum preparation and inactivation always cause lose of lots of herbal components. Recently finger printing analysis using HPLC-MS and antileukemic proliferation experiments showed that the results obtained from serum pharmacological method might be incorrect. We propose that the ex vivo experiments on multiple levels are necessary to elucidate the pharmacological actions and their mechanisms of medical herbs and believe that the pharmacological method using plasma absorbed herbal components should be better than that using serum.