Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies / 中国结合医学杂志

OBJECTIVE@#To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).@*METHODS@#Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.@*RESULTS@#The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs.@*CONCLUSIONS@#STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

A proposed mechanism by which Qishen Yiqi dropping pill improves cardiac energy metabolism in rats with heart failure based on metabolomics and network pharmacology / 药学学报

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial / 中西医结合学报

BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

Shexiang Tongxin Dropping Pill () Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats.@*METHODS@#Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg@*RESULTS@#The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01).@*CONCLUSION@#STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.

Shexiang Tongxin Dropping Pill () Protects against NaSO-Induced Hypoxia-Reoxygenation Injury in H9c2 Cells / 中国结合医学杂志

OBJECTIVES@#To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STP) on NaSO-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells.@*METHODS@#The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following NaSO-induced hypoxia using Hoechst staining, annexin V/propidium iodide (PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis.@*RESULTS@#STP pretreatment significantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by NaSO treatment (P<0.05). In addition, STP pretreatment attenuated NaSO-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax, and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells (P<0.05).@*CONCLUSIONS@#STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis. These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.

Clinical Evidence Evaluation of Shexiang Tongxin Dropping Pill for Slow Blood Flow after PCI / 世界科学技术-中医药现代化

Objective: To evaluate the efficacy and safety of Shexiang Tongxin dropping pill (ShXT) in the treatment ofslow blood flow after PCI (Percutaneous Transluminal Coronary Intervention), and to provide evidence for clinicaltreatment of patients with slow blood flow after PCI or to provide evidence for further research and design. Methods: "Shexiang Tongxin", "PCI", "percutaneous coronary intervention", "shexiangtongxin", "shexiang tongxin", "percutaneouscoronary intervention" were used as key words. Randomized controlled clinical trial (RCT), system evaluation, retrospective case analysis and case-control trials of randomized controlled clinical trials were searched in the databasesof Pubmed, Cochrane, web of science, CNKI, WIP, CBM, and other databases. Cochrane risk assessment tool and NOSrating scale were used to evaluate the quality of literature, and the classification of literature evidence was evaluatedaccording to Oxford criteria of evidence classification and recommended opinion strength in 2001. Results: A total of 3 articles of RCT related to the subject were selected, including 1 case control trial, including 335 patients. The resultsshowed that: (1) The frequency of thrombolysis, heart ejection fraction and TIMI blood flow in patients with slow coronaryartery flow after treatment with Shexiang Tongxin dropping pills were significantly higher than those before treatment. (P ＜ 0.05) . (2) After treatment with Shexiang Tongxin dropping pills, the effective rate of clinical symptoms was 97.8％, which was higher than that of the treatment group 11.1％. (3) There were no adverse reactions in the ShXT group duringthe treatment period. Conclusion: The efficacy and safety of Shexiang Tongxin dropping pills for patients with slow bloodflow after PCI were good. However, the dosage, method, period and outcome of the clinical study of slow blood flow afterPCI were not uniform because of the dosage, method, period of taking Shexiang Tongxin dropping pills in patients afterPCI. It is suggested that the clinical study should be aimed at the choice of different dosages before and after theadministration of drugs. The multicenter prospective randomized controlled trial can provide more evidence for itsclinical application.

Study on mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction / 中华危重病急救医学

Objective To approach the mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction. Methods Sixty clean healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and observation group (each n = 20). The rat model of acute myocardial infarction (AMI) was established by ligation of left anterior descent (LAD) branch of coronary artery. After modeling, the rats in observation group were given 0.135 g/kg of Qishen Yiqi dropping pills, and sham operation group and model group were administered the same amount of normal saline, once a day for consecutive 28 days. At the end of treatment, the levels of serum inflammatory factors of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA); the changes of the indexes of hemodynamic [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximal rate of increase/decrease in left ventricular pressure (±dp/dt max)], the ratio of the heart weight/body weight, and the ratio of the left ventricular weight/heart weight (LVW/HW), the myocardial infarction area, myocardial histopathological changes were observed in the three groups; myocardial tissues inflammatory related factors [the mRNA and protein expressions of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX)], and the expression levels of transforming growth factor-β (TGF-β)/Smads signal transduction pathway related protein (TGF-β1, Smad2/3, Collagen Ⅰ, Collagen Ⅲ ) and cell apoptosis related factors (Bcl-2, Bax) protein were measured. Results Compared with the sham operation group, levels of serum inflammatory factors, the index of LVEDP, the ratio of the heart weight/body weight, LVW/HW, myocardial infarction area, the mRNA and protein expression levels of inflammatory factors in myocardium, the expression levels of TGF-β/Smads signal transduction pathway related protein and the cell apoptosis related factors protein in model group were all significantly elevated, while LVSP and ±dp/dt max were obviously decreased in model group. Compared with the model group, the levels of inflammatory factor in serum [LTB4 (ng/L): 370.11±46.98 vs. 633.23±83.37, PGE2 (ng/L):48.75±26.35 vs. 131.25±29.75, TNF-α (μg/L): 177.28±22.65 vs. 248.47±16.21, IL-6 (μg/L): 493.22±165.99 vs. 638.41±191.66], LVEDP [mmHg (1 mmHg = 0.133 kPa): -2.03±2.98 vs. 7.03±1.39], the ratio of the heart weight/body weight [(6.53±0.11)% vs. (7.14±0.24)%], LVW/HW (0.26±0.01 vs. 0.32±0.02), myocardial infarction area [(27.21±2.87)% vs. (44.98±1.52)%], mRNA and protein expression of myocardial inflammatory factors, the expression of TGF-β/Smads signal transduction pathway related protein, and the protein expression of Bax were all significantly decreased in observation group (all P < 0.05), LVSP (mmHg: 129.01±11.93 vs. 108.11±12.69), the +dp/dt max (mmHg/s: 3101.3±378.6 vs. 2105.3±245.9), the -dp/dt max (mmHg/s: 2612.4±249.7 vs. 1654.4±188.1), while the protein expression of Bcl-2 in observation group were obviously increased (all P < 0.05). It was demonstrated by hematoxylin-eosin (HE) staining that there were no obvious pathological changes in the sham operation group; obvious infiltration of inflammatory factors in myocardium was shown in model group; pathological changes in the observation group were significantly improved as compared with those in the model group. It was shown by Masson staining that there were slight hyperplasia of myocardial fibers and no obvious pathological changes in the sham operation group. Severe collagen hyperplasia was found in model group, and the degree of fibrosis in the observation group was significantly improved. Conclusions Qishen Yiqi dropping pills can reduce the degree of myocardial fibrosis and inhibit the ventricular remodeling via TGF-β/Smads signal transduction pathway. The dropping pills can also suppress the release of inflammatory factors by reducing cPLA2 to decrease the inflammatory response and inhibit apoptosis and alleviate myocardial injury by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

Optimization of Formulation Technology of the Ibuprofen Sustained-release Dropping Pill and Evaluation of Its in vitro Drug-release Behavior / 中国药房

OBJECTIVE:To optimize the formulation technology of Ibuprofen sustained-release dropping pill and evaluate its in vitro drug-release characteristics. METHODS:Using stearic acid as sustained-release matrix,polyethylene glycol 6000 as imme-diate-release matrix,melting method was used to prepare the Ibuprofen sustained-release dropping pill. Using the comprehensive scores of roundness,weight difference,drug loading rate,in vitro drug-release time as indexes,drug-matrix mass ratio,liquid tem-perature,condensation temperature,dropping distance as factors,orthogonal test was adopted to optimize the formulation technolo-gy,and verification test was conducted. In media of deionized water,hydrochloric acid solution (pH 1.2),phosphate buffer (pH 4.5,6.8),the in vitro drug-release were compared between self-made sustained-release dropping pill and commercially available Ibuprofen sustained-release capsule,which were fitted for former drug-release behavior. RESULTS:The optimal formulation tech-nology was as follows as mass ratio of ibuprofen-polyethylene glycol 6000-stearic acid of 4.0:15.3:0.7,liquid temperature of 83 ℃,condensation temperature of 8 ℃,and dropping distance of 11 cm. The weight difference of prepared 3 batches of Ibupro-fen sustained-release dropping pill was 2.067%(RSD=1.19%),roundness was 96.73%(RSD=0.28%),drug loading rate was 96.31%(RSD=0.19%),cumulative release rate in 12 h was 93.05%(RSD=0.81%). The f2 values of self-made sustained-re-lease dropping pill and commercially available Ibuprofen sustained-release capsule were greater than 50,the former one fitted more into Higucci equation(r=0.9881-0.9972). CONCLUSIONS:The formulation technology of Ibuprofen sustained-release dropping pill is successfully optimized,and in vitro drug-release behavior of prepared sustained-release dropping pill is similar to commercial-ly available Ibuprofen sustained-release capsule.

Optimization of Formulation Technology of the Ibuprofen Sustained-release Dropping Pill and Evaluation of Its in vitro Drug-release Behavior / 中国药房

OBJECTIVE:To optimize the formulation technology of Ibuprofen sustained-release dropping pill and evaluate its in vitro drug-release characteristics. METHODS:Using stearic acid as sustained-release matrix,polyethylene glycol 6000 as imme-diate-release matrix,melting method was used to prepare the Ibuprofen sustained-release dropping pill. Using the comprehensive scores of roundness,weight difference,drug loading rate,in vitro drug-release time as indexes,drug-matrix mass ratio,liquid tem-perature,condensation temperature,dropping distance as factors,orthogonal test was adopted to optimize the formulation technolo-gy,and verification test was conducted. In media of deionized water,hydrochloric acid solution (pH 1.2),phosphate buffer (pH 4.5,6.8),the in vitro drug-release were compared between self-made sustained-release dropping pill and commercially available Ibuprofen sustained-release capsule,which were fitted for former drug-release behavior. RESULTS:The optimal formulation tech-nology was as follows as mass ratio of ibuprofen-polyethylene glycol 6000-stearic acid of 4.0:15.3:0.7,liquid temperature of 83 ℃,condensation temperature of 8 ℃,and dropping distance of 11 cm. The weight difference of prepared 3 batches of Ibupro-fen sustained-release dropping pill was 2.067%(RSD=1.19%),roundness was 96.73%(RSD=0.28%),drug loading rate was 96.31%(RSD=0.19%),cumulative release rate in 12 h was 93.05%(RSD=0.81%). The f2 values of self-made sustained-re-lease dropping pill and commercially available Ibuprofen sustained-release capsule were greater than 50,the former one fitted more into Higucci equation(r=0.9881-0.9972). CONCLUSIONS:The formulation technology of Ibuprofen sustained-release dropping pill is successfully optimized,and in vitro drug-release behavior of prepared sustained-release dropping pill is similar to commercial-ly available Ibuprofen sustained-release capsule.

The effect of combinatory use of small dosage of aspirin with compound danshen dropping pills on type 2 diabetes patients' hypercoagulation blood / 重庆医学

Objective To study the joint effect of small dosages of Aspirin and compound Danshen dropping pills on type 2 diabetes(T2DM) patients'and impaired glucose tolerance(IGT) patients' hypercoagulation blood.Methods The study followed diagnostic standards for T2DM by World Health Organization (WHO) in 1999,and randomly selected two groups of clinical patients:one had 63 patients with IGT and the other contained 68 patients with T2DM.Both groups took compound Danshen dropping pills with the total dosage of 10 pills each time,3 times per day,for continuum of 3 months.After that both groups stopped medication for 7 days,then began taking Aspirin after meal,with the dosage of 100 mg per day,for a continuum of 3 month.After that both groups stopped the medication for 7 days,then both group continued to take same dosage of ASA with addition of compound Danshen dropping pills of total amount of 10 pills per each time,3 times per day,for acontinuum of 3 months.Each medication period (ev ery 3 months) was monitored for platelet count (PET),prothrombin time (PT),kaolin partial thromboplastin time (APPT),The effective rate of anticoagulation for both groups were then calculated.Results The difference of PT、APTT between before and after taking single dosage of ASA for patients with impaired glucose tolerance (IGT) was statistically significant (P＜0.05),while patients with T2DM had no significant difference before and after taking same single dosage of ASA.Similarly, both groups with single dosage of compound Danshen dropping pills had no significant difference between before and after taking the medication.However,the difference of PT、APTT between before and after taking the combination of Aspirin and Danshen dropping pills of both groups were statistically significant (P＜0.05).IGT group with single dosage of ASA had an effective rate of 71.4％ for anti coagulation,while T2DM group with the same dosage reached 23.8％.The IGT group with combinatory dosage of ASA and Danshen dropping pills reached an effective rate of 100％ for anticoagulation,while T2DM group with the same dosage was 86.7％.The difference between those effective rates of anticoagulation was statistically significant in different medicine takeways of two groups (P＜0.05).Conclusion The combinatory use of small dosage of Aspirin with compound Danshen dropping pills had evident effect to improve IGT and hypercoagulation blood of T2DM patients who had good control of their blood glucose.

Rapid Analysis and Identification of Absorbed Components and Their Metabolites of Yuanhu Zhitong Dropping Pill in Rat Plasma and Brain Tissue Using UPLC-Q-TOF/MS with Multivariate Statistical Analysis / 中草药·英文版

Objective: To establish an effective approach for rapid and comprehensive analysis on the absorbed and metabolic components in rats after ig administration of Yuanhu Zhitong Dropping Pill (YHZT). Methods: Based on the combination of UPLC-Q-TOF/MS and multivariate statistical analysis, the absorbed prototype constituents and their metabolites in rat plasma were rapidly analyzed and identified, and the components absorbed into brain were further identified by comparing the extracted ion chromatograms (EICs) of control and brain tissue samples of dosed rats. Results: A total of 38 YHZT-related xenobiotic compounds were detected and identified as the potential bioactive constituents in rat plasma, including 24 absorbed prototype constituents and 14 metabolites. In particular, of all prototype constituents, 14 were also detected in rat brain tissue, indicating that they could penetrate the blood-brain barrier and enter into brain. Conclusion: An effective method is established and applied to analyze the potential bioactive constituents in YHZT, which provides a pathway to further investigate the pharmacological pattern and mechanism of YHZT.

Neuroprotective effects of Shunaoxin Dropping Pill on D-galactose induced Alzheimer's disease rat model and their mechanisms / 中草药

Objective: To investigate the neuroprotective effects of Shunaoxin Dropping Pill (SDP) on Alzheimer's disease (AD) rats induced by D-galactose their mechanisms. Methods: Rats were ip given D-gal (100 mg/kg) for 60 d to induce the prominent changes of AD in the early stage. Morris water maze was used to investigate neurobehavioral changes, superoxide dismutase (SOD) and malondialdehyde (MDA) kits were used to determine the indicators of oxidative stress, immunohistochemistry was used to evaluate the expression of GFAP and Caspase-3, and HE staining was used to observe the morphological changes in hippocampal region. Results: SDP treated group significantly decreased latency and increased the bouts of cross platform in Morris water maze experiment (P < 0.05), improved the morphological changes in hippocampal region and significantly increased the content of SOD content (P < 0.05), decreased the content of MDA (P < 0.05), and alleviated the neuron death. Conclusion: SDP has the certain therapeutic effect on prominent changes of AD in the early stage through its anti-oxidant stress effect. Our study provides the first piece of evidence supporting the potential use of SDP in the treatment of AD in clinic.

Effect of Shunaoxin Dropping Pill on blood pressure and cardiac protection in spontaneously hypertensive rats / 中草药

Objective: To evaluate the effect of Shunaoxin Dropping Pill (SDP) on blood pressure and cardiac protection in spontaneously hypertensive rats (SHRs). Methods: The SHRs were randomly divided into three groups, model (M) group, SDP group, and valsartan (VL) group. Non-invasive blood pressure instrument was used to measure blood pressure. Serum content of nitric oxide synthase (NOS) and angiotensin II (Ang II) were measured using kits for 6 weeks after ig administration. Doppler echocardiography was used to evaluate left ventricular weight, and HE staining was used to assess aortic and cardiac morphology. Results: The blood pressure of SHRs decreased to minimum 1 h after ig administration of SDP (800 mg/kg). Long-term use of SDP could stabilize blood pressure of SHRs. Serum content of NOS in SDP group was significantly more than that in M group (P < 0.05). The serum content of Ang II in SDP group was significantly less than that in M group (P < 0.05). The left ventricular weight of SDP group was significantly lower than that in M group (P < 0.05). SDP administered group can improve myocardial and aortic morphology abnormalities caused by hypertension. Conclusion: SDP has a certain therapeutic effect on hypertensive with myocardial hypertrophy rats, it can be used as a potential drug on hypertensive disorders associated with cardiac hypertrophy.

Re-evaluation on preparation technology of compound Chuanxiong dropping pills / 药学实践杂志

Objective To optimize the preparation technology of compound Chuanxiong dropping pills .Methods Ratio of intermediate material to matrix ,dripping temperature and condensate temperature were used as factors ,with spherical de‐gree ,pill weight variatcon ,dissolve time limit coefficient and appearance quality as indexes ,the forming technology of compound Chuanxiong dropping pill was optimized by orthogonal test .The dropping preparation technology was optimized using dropping distance ,dropping speed as factors .Results The optimal preparation conditions were as follows:ratio of intermediate material to matrix was 1:2 ,dropping temperature was 80 ℃ ,temperature of condensate was 15‐20 ℃ ,dropping distance was 5 cm , dropping speed was 40 drops/min .Conclusion The preparation technology was reasonable ,simple and easy to control for the preparation of compound Chuanxiong dropping pills .

Interaction of Shunaoxin Dripping Pill and Warfarin sodium on anticoagulant applications / 中草药

Objective: To study the anticoagulant effect of Shunaoxin Dropping Pill (SDP) alone or in combination with Warfarin sodium on platelet aggregation and provide the experimental support for the clinical safety of medication. Methods: Experiments were carried out in control group, low-dose SDP group, high-dose SDP group (45.36 and 90.72 mg/kg), and Warfarin sodium (clinical equivalent dose 0.4 mg/kg) group, Combined administration with low-dose SDP and high-dose SDP groups+clinical equivalent dose of Warfarin sodium. We determined the platelet aggregation rate of rats in the control group, low-dose SDP group, and high-dose SDP group in vitro by turbidimetry. We made iac administration of SDP and Warfarin sodium for 3 d, and took abdominal aortic blood for separating the platelets and used nephelometry for determining platelet aggregation rate; We separated serum and used semi-automatic coagulation analyzer to test APTT, PT, and TT. Results: Compared with the control group, SDP had the strong anti-platelet aggregation in vitro and could inhibit the increase of platelet aggregation in vivo slightly with the dose increasing. SDP could prolong APTT, PT, and PT; Compared with the single drug group, the combination therapy had no obvious effect on the platelet aggregation but could significantly extend the APTT, PT, and TT. Conclusion: SDP has some inhibition on platelet aggregation with anticoagulant effect; Combined with Warfarin sodium, SDP has a synergistic interaction on anticoagulant effect with Warfarin sodium.

Therapeutic effects of Qishen Yiqi Dropping Pill on myocardial injury induced by chronic hypoxia in rats / 中国天然药物

The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley (SD) rats were randomly divided into three groups: the control, model, and treatment groups (n = 10 per group). The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill (35 mg·kg(-1)·d(-1)) for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor 1α (HIF-1α) were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1α expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular diseases.

Extraction process for Ligusticum chuanxiong Hort. and Corydalis yanhusuo of Kexintong dropping pill / 国际药学研究杂志

Objective: To optimize the extraction technology of ferulic acid (FA) in Ligusticum chuanxiong Hort. and tetrahydropalmatine in Corydalis yanhusuo from Kexintong dropping pill. Methods: The extraction technology of L. chuanxiong was screened by the orthogonal test. The extration was refined with the high aperture jaffaite. The technology parameter for extracting C.yanhusuo by the classic method of acidic dissolution and alkaline precipitation was optimized by the orthogonal test. Results: The more effective way to extract FA from L. chuanxiong was to extract with 12 times amount of 75% alcohol under reflux for 3.5 h. The chuanxiong extract of pH 3 at a flow rate of 5 ml/min on DM-130 macroporous resin column, was eluted with 80% ethanol. The eluent was collected and dried under vacuum. The more effective way to extract tetrahydropalmatine in C. yanhusuo was extracted with 22 times amount of acidic water (pH 4) for 3 h. Conclusion: The optimum extraction is reasonable and practicable with high extraction ratio.

Preparation technology of sustained-release dropping pills of trimebutine maleate / 中国药学杂志

OBJECTIVE: According to the feature that trimebutine maleate has poor aqueous solubility, low bioavailability when taken orally, short biological half-life (2.7 h), sustained-release dropping pills were prepared to achieve release slowly, reduce the blood drug concentration fluctuations and decrease frequency of use.

Effects of Qishen Yiqi Dropping Pill Combined with Telmisartan on Early Diabetic Nephropathy and Changes of Oxidative Stress Indicators / 中国中医药信息杂志

Objective To observe the clinical efficacy of Qishen Yiqi Dropping Pills combined with telmisartan on early diabetic nephropathy with Qi deficiency and blood stasis syndrome and changes of oxidative stress indicators. Methods Sixty patients with early diabetic nephropathy of qi-yin deficiency and blood stasis syndrome were randomly divided into treatment group (30 cases) and control group (30 cases). Both groups were given diabetes education, diabetes diet control and insulin injection. Patients in the control group took telmisartan orally, and patients in the treatment group were given Qishen Yiqi Dropping Pills additionally. The treatment course was 12 weeks. The indicators were observed before and after treatment including blood pressure (BP), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), urinary albumin excretion rate (UAER), urinary 8-iso-PGF2α excretion rate, serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malonaldehyde (MDA), and the clinical efficacy was evaluated. Results The total effective rate of the treatment group was significantly higher than that of the control group, with statistical significance (Z=2.822, P=0.005). After treatment, the indicators including BP, FBG, HbA1c, serum MDA, UAER and urinary 8-iso-PGF2α excretion rate all decreased significantly in both groups (P0.05). However, serum MDA, UAER, and urinary 8-iso-PGF2αexcretion rate were significantly lower (P<0.05), and serum SOD and GSH-Px were significantly higher in treatment group than control group (P<0.05). Conclusion Qishen Yiqi Dropping Pill combined with telmisartan is effective in reducing proteinuria in patients with early diabetic nephropathy of qi-yin deficiency and blood stasis syndrome. Its protective mechanism for kidney is possibly related to inhibiting oxidative stress injury at the early stage of diabetic nephropathy.

Extraction process for Ligusticum chuanxiong Hort. and Corydalis yanhusuo of Kexintong dropping pill / 国际药学研究杂志

Objective To optimize the extraction technology of ferulic acid (FA) in Ligusticum chuanxiong Hort. and tetrahydropalmatine in Corydalis yanhusuo from Kexintong dropping pill. Methods The extraction technology of L. chuanxiong was screened by the orthogonal test. The extration was refined with the high aperture jaffaite. The technology parameter for extracting C. yanhusuo by the classic method of acidic dissolution and alkaline precipitation was optimized by the orthogonal test. Results The more effective way to extract FA from L. chuanxiong was to extract with 12 times amount of 75% alcohol under reflux for 3.5 h. The chuanxiong extract of pH 3 at a flow rate of 5 ml/min on DM-130 macroporous resin column, was eluted with 80% ethanol. The eluent was collected and dried under vacuum. The more effective way to extract tetrahydropalmatine in C. yanhusuo was extracted with 22 times amount of acidic water (pH 4)for 3 h. Conclusion The optimum extraction is reasonable and practicable with high extraction ratio.