Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats

Objective： To investigate the influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells（CD4^＋CD25^＋ Tr） of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods： 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids （BALF） were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain （HE）. Flow cytometry was used to detect the CD4^＋CD25^＋ Tr ratio in peripheral blood mononuclear cells （PBMCs）. Results： Total cell, the percentage of lymphocytes, neutrophils and eosinophils （Eos） in BALF of Danshen Injection-treated group were lower than that in asthma group （P〈0.05, P〈0.01）. Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^＋CD25^＋ Tr of asthma group was lower than that of control and Danshen Injection treated group （P〈0.05）. Conclusion： Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^＋CD25^＋ Tr.

Pharmacokinetic parameters investigation on interaction between Danshen injection and Honghua injection

OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the useful drugs for the.As the common TCM injections,Danshen injection is often combined with Honghua injection to treat cardiovascular disease.The purpose of this study was to investigate the pharmacokinetic parameters of Honghua injection combined with Danshen injection when they were coadministered intravenously in human and rats through the tail vein.METHODS Single and multiple doses of Danshen injection to study Danshen injection on Honghua injection pharmacokinetics parameters and single and multiple doses of Honghua injection to study Honghua injection on Danshen injection pharmacokinetics parameters.The plasma concentrations of hydroxysafflor A(HSYA)and tanshinol and salvianolic acid B were determined by the reliable high-performance liquid chromatography(HPLC)method.The concentrations of HSYA in urine of rats and human were also determined by HPLC method.DAS 2.1.1software was adopted for calculating the pharmacokinetic parameters.RESULTS The simultaneous intravenous Honghua injection and salvia miltiorrhiza injiection significantly altered the pharmacokinetic parameters of both injections when compared with the individual intravenous administration of each injection.The area under the concentration-timecurve(AUC)and maximum plasma concentration(Cmax)of HSYA and tanshinol and salvianolic acid B were significantly increased.The cumulative urine excretion of HSYA in human and rats during 24 h was decreased after two drugs were administered simultaneously by the intravenous.CONCLUSION Honghua injection and Danshen injection interact with each other following simultaneous intravenous and they have a synergistic action.This experiment has identified the pharmacokinetic parameters and provided a rationale for the clinical use of the drug combination.

Clinical characteristics of Danshen Ligustrazine injection in the treatment of coronary heart disease with hypertension-A real world study

Objective:To explore the characteristics and rules of Danshen Ligustrazine Injection in the treatment of coronary heart disease with hypertension.Methods:From the information systems of 12 tertiary tier-one hospitals across the country,we extracted the medical data of the application of Danshen Ligustrazine Injection in the treatment of patients with coronary heart disease and hypertension.After normalization,the model was established by Apriori algorithm,and the association rules were analyzed by Clementine 12.0 software.Results:Most of the 1928 patients were between 75 and 90 years old(54.26%).There were more males than females,most with type 2 diabetes,cerebral infarction,etc.Each dose was more than 10 mL(52.78%).Aspirin enteric-coated tablets(67.63%),L-carnitine injection(58.77%),and atorvastatin calcium capsules(50.93%)were often used in combination with safflower yellow pigment(22.20%),Shexiang Baoxin Pill(16.55%),Suxiao Jiuxin Pill(15.09%);the most commonly used combination of western medicine was anticoagulant thrombolytic and antiplatelet drugs(85.84%),and the type of Chinese medicine was Huoxuehuayu(72.98%);The most common combination of two western medicines was L-carnitine injection+aspirin enteric-coated tablets,with a support of 41.9%;The most common combination of two Chinese and western medicines is western medicine·anti-anginal medicine+western medicine·anticoagulant thrombolytic and antiplatelet drugs with a support of 67.6%.Conclusion:Danshen Ligustrazine injection is mainly used in elderly patients with coronary heart disease and hypertension,with many comorbidities.The dosage standard needs to be optimized.The combination of drugs and guidelines should coordinate with each other,which provide clues for clinical diagnosis and treatment and optimization of medication.

Effect of Compound Danshen Injection Combined with Labetalol on Liver Function and Placental Growth Factor in Patients with Eclampsia

Objective: To explore the effect of Compound Danshen Injection combined with Labetalol on liver function and placental growth factor in patients with eclampsia. Methods: Seventy patients with eclampsia who were treated in the Hospital from February 2017 to February 2019 were enrolled. The patients were divided into two groups according to the random number table, with 35 cases in each group. The Observation group was treated with Labetalol, and the combined therapy group was treated with Compound Danshen Injection combined with Labetalol. The liver function [alanine aminotransferase, aspartate aminotransferase, total protein, and albumin], hemorheology indicators, placental growth factor and serum insulin-like growth factor-1 and clinical indicators in the two groups were analyzed. Results: After treatment, the levels of alanine aminotransferase and aspartate aminotransferase in the combined therapy group were significantly lower than those in the Observation group. The levels of total protein and albumin in the combined therapy group were significantly higher than those in the Observation group (P<0.05). After treatment, the high-cut and low-cut whole blood viscosity, plasma viscosity and erythrocyte rigidity index in the combined therapy group were significantly lower than the Observation group, and the difference was statistically significant (P<0.05). After treatment, the levels of PLGF and IGF-1 in the combined therapy group were significantly higher than those in the Observation group, and the difference was statistically significant (P<0.05). After treatment, the gestational age, neonatal weight index, placental weight and neonatal 1 min Apgar score in the combined therapy group were significantly higher than the Observation group, and the difference was statistically significant (P<0.05). Conclusion: For patients with eclampsia, Compound Danshen Injection combined with Labetalol is with great safety, which can help stabilize their condition, and improve their liver function and placental growth factor status.

Efficacy of Danshen Injection Combined with Phosphocreatine Disodium in Treating Frequent Premature Contractions during Pregnancy and Its Effects on Maternal and Infant Outcomes

[Objectives]To explore the efficacy of Danshen Injection combined with phosphocreatine disodium in treating frequent premature contractions during pregnancy and its effect on maternal and infant outcomes.[Methods]A total of 200 pregnant women with normal pregnancy and frequent premature contractions who were treated in the outpatient department of internal medicine in Women and Children's Hospital of Hubei Province and Xinzhou District People's Hospital of Wuhan Central Hospital during September 2015 and October 2018 were selected and randomly divided into the control group and observation group,100 cases for each group.The observation group was treated with Danshen Injection combined with phosphocreatine disodium,and the control group was treated with phosphocreatine disodium alone.The course of treatment in both groups was one week.During the treatment,the changes of heart rate,heart rhythm,electrocardiogram and 24-h dynamic electrocardiogram(DCG)of both groups were observed.[Results]After treatment,the clinical efficacy of the observation group was better than that of the control group,and the difference was statistically significant(P<0.01).There were no adverse drug reactions in both groups.However,in the control group,non-sustained ventricular tachycardia(NSVT)was found in 24-h dynamic electrocardiogram(DCG)of 2 pregnant women with premature ventricular contraction.The pregnancy process was smooth,with full-term natural delivery and no fetal malformation.There was no significant difference in gestational age and neonatal weight between the two groups(P>0.05).However,there was a statistically significant difference in Apgar score between the two groups(P<0.05).During the 6-month postpartum follow-up,the mother and child were unharmed,and examination of repeated electrocardiograms showed that the conditions were normal.[Conclusions]Danshen Injection combined with phosphocreatine disodium has better efficacy in the treatment of frequent premature contractions during pregnancy and the maternal and infant outcomes than the treatment with phosphocreatine disodium alone,and it has good safety and can prevent premature contractions from progressing to tachyarrhythmias.

Effect of Salvia Miltiorrhiza Injection on Blood Pressure and Cardiac Function in Rats with Gestational Hypertension and Preeclampsia

Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.

Danshen Injection as Adjuvant Treatment for Unstable Angina Pectoris： A Systematic Review and Meta-analysis

To systematically evaluate the clinical effectiveness and safety of Danshen Injection ( DS) as one adjuvant treatment for conventional therapy with Western medicine (WM) for unstable angina pectoris (UAP). Using literature databases, a thorough and systematic retrieval of randomized controlled trials (RCTs) comparing DS plus WM with WM was conducted from inception to April 2015. The extracted data from included studies was analyzed by Review Manager 5.2 software. The Cochrane risk of bias tool was used to assess the quality of included studies, and Begg's and Egger's tests conducted by Stata 12.0 were used to evaluate the potential presence of publication bias. A total of 17 RCTs, which involving 1,433 participants, were identified and reviewed. The meta-analysis indicated that the combined use of DS and WM was significantly superior to WM alone for UAP in terms of the total effectiveness rate of angina pectoris [risk ratio (RR) =1.23, 95% confidence interval (CI): 1.17, 1.29, P < 0.01] and the total effectiveness rate of electrocardiogram (ECG) [RR=1.18, 95%CI: 1.06, 1.30, P=0.001]. Additionally, DS could also further reduce the content of fibrinogen, adjust blood lipid level, correct T wave inversion, and so on. Fifteen adverse drug reactions were reported in two studies, Four of which appeared in the experimental group. Based on the systematic review, the combined use of DS and WM was more effective than WM alone, it can be further widely used in clinic, however, there was no exact conclusion for its safety.

Effects of Danshen Injection(丹参注射液) on Inhibiting Proliferation and Inducing Apoptosis through Down-Regulation of Mutant JAK2 Gene and Its Protein Phosphorylation in Human Erythroid Leukemic Cells

Objective： To explore the effects of Danshen Injection （丹参注射液） on inhibition proliferation, inducing apoptosis and its possible mechanisms on human erythroid leukemic （HEL） cells. Methods： The commercial Chinese patent medicine of Danshen Injection was extracted and isolated from Chinese herb of Salvia miltiorrhiza bung. The inhibition effects of proliferation were assayed by 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （M＇l-r） method in HEL cells treated by Danshen Injection at various concentrations for 48 h. The cellular apoptosis was observed in morphology, analyzed by flow cytometry with annexin V and propidium iodide （PI） staining, and examined by DNA degradation ladder on agarose gel electrophoresis. Meanwhile, the expression levels of mutant Janus kinasez （JAK2） gene and phosphorylation-JAK2 （P-JAK2） protein were detected by allele specific-polymerase chain reaction and Western blot. ]Results： The proliferation of HEL cells was effectively inhibited by Danshen Injection in a dose-dependent manner, with suppression rates from 19.46 ± 2.31% to 50.20 ± 5.21%. Typical apoptosis cells was observed in Danshen Injection treated HEL cells, the rates of annexin V positive cells increased obviously in a dose-dependent manner, as well as the DNA degradation ladder of apoptosis revealed on gel electrophoresis. The expression levels of mutant JAK2 gene and P-JAK2 protein reduced gradually with increasing dosage of Danshen injection. Conclusion： Danshen Injection could not only significantly inhibit the proliferation, but also induce apoptosis in HEL cells; down-regulation of the mutant JAK2 gene and P-JAK2 protein expressions are probably one of its molecular mechanisms.

Toxicity of Danshen Injection in Beagle's Dogs by Repeated iv Injection

Objective To re-evaluate the potential toxicity of Danshen Injection(DI) in Beagle's dogs by repeated iv injection.Methods DI was iv given to the dogs at the doses of 0,1.6,5.4,and 16.0 g/(kg·d)(4 per sex per group) for 13weeks.During the test period,the clinical signs,mortality,body weights,food consumption,rectal temperature,ophthalmoscopy,electrocardiography,urinalysis,hematology,serum biochemistry,organ weights,gross findings,and histopathology were examined.Results Dogs iv given with DI at the doses of 0,1.6,5.4,and 16.0 g/(kg·d) for13 weeks had no drug-related changes in mortality,body weight,food consumption,temperature,electrocardiography,ophthalmoscopy,urinalysis parameters,and organ weights.The hematological parameter data showed a significant decrease in red blood cells and hemoglobin concentration in the high-dose group and a significant increase in activated partial thromboplastin time suggesting an effect on haemopoiesis.For biochemical parameters,a significant decrease in glucose and a significant increase in total bilirubin were observed in the high-dose group,and the latter was considered to be toxicologically insignificant as lack of histopathological correlate.However,the histopathological examinations of the injection site showed that DI could cause dose-dependent focal inflammation.Conclusion That the iv injection with DI into dogs at 16 g/(kg·d) for 13 weeks could cause the decreases in red blood cell parameters and glucose,as well as the lesions of the injection site.The no observed adverse effect level is5.4 g/(kg·d),which suggests that safe clinical dosing be possible.