The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (AngⅡ)-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate (STS) in the primary culture of neonatal rat cardiomyocyte...The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (AngⅡ)-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate (STS) in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction (RT-PCR). It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly (P〈0.01). After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group (P〈0.01). After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group (P〈0.05). After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ (P〈0.05 or P〈0.01). It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.展开更多
Objective: To systematically evaluate the effectiveness and safety of Sodium Tanshinone ⅡA Sulfonate Injection(STS) as one adjuvant therapy for treating unstable angina pectoris(UAP). Methods: Randomized contro...Objective: To systematically evaluate the effectiveness and safety of Sodium Tanshinone ⅡA Sulfonate Injection(STS) as one adjuvant therapy for treating unstable angina pectoris(UAP). Methods: Randomized controlled trials(RCTs) of UAP treated by STS were searched in the China National Knowledge Infrastructure Database(CNKI), VIP Database for Chinese Technical Periodicals(VIP), Wanfang Database, the Chinese Biomedical Literature Database(CBM), Web of Science, the Cochrane Library, Embase, and Pub Med, which from inception to January, 2016. The Cochrane Risk Assessment Tool was used to evaluate the methodological quality of the RCTs. The Review Manager 5.3 software was used to conduct the metaanalysis. Results: The results showed that 17 RCTs involving 1,372 patients were included. The meta-analysis indicated that the combined use of STS and Western medicine(WM) in the treatment of UAP can obviously improve the total effective rate [risk ratio(RR)=1.31, 95% confidence interval(CI)(1.24,1.39), P〈0.0001], and the total effective rate of electrocardiogram [RR=1.43, 95% CI(1.30,1.56), P〈0.0001], decrease the level of CRP [mean difference(MD)=–3.06, 95%CI(–3.85, –2.27), P〈0.00001], fibrinogen [MD=–1.03, 95% CI(–1.16, –0.89), P〈0.00001], and whole blood high shear viscosity [MD=–0.70, 95% CI(–0.92, –0.49), P〈0.00001]. Additionally, the occurrence of adverse drug reaction of the experimental group was significantly higher than that of the control group [RR=3.57, 95% CI(1.28, 9.94), P〈0.05]. Conclusions: Compared with WM, the combined use of STS was more effective.展开更多
To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal l...To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture(CLP).Rats were randomly divided into 3 groups:sham operated group(S),sepsis group(CLP) and STS treatment group(STS).STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay(ELISA).The expression of intercellular adhesion molecule-1(ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB(NF-κB) and tissue factor(TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP(P0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α(P0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.展开更多
OBJECTIVE: To investigate the efficacy and safety of Sodium tanshinone ⅡA sulfonate(STS) plus the conventional treatment on acute myocardial infarction(AMI) patients.METHODS: We searched several electrical databases ...OBJECTIVE: To investigate the efficacy and safety of Sodium tanshinone ⅡA sulfonate(STS) plus the conventional treatment on acute myocardial infarction(AMI) patients.METHODS: We searched several electrical databases and hand searched several Chinese medical journals up to January 2019. Randomized controlled trials(RCTs) comparing STS plus conventional treatment with conventional treatment were retrieved.Study screening, data extraction, quality assessment, and data analysis were conducted in accordance with the Cochrane standards.RESULTS: Sixteen trials involving 1383 people were included. The Meta-analysis showed STS combined with conventional treatment was a better treatment option than conventional treatment alone in reducing the risk of mortality, heart failure, arrhythmia and shock. In addition, STS was associated with improvement in left ventricular ejection fraction(LVEF) and left ventricular end diastolic dimension(LVEDD). No significant difference of STS was found on recurrent angina and recurrent AMI. However,the safety of STS remained uncertain for limited data.CONCLUSION: Compared with conventional treatment alone, STS combined with conventional treatment may provide more benefits for patients with AMI. Due to the fact that the overall quality of all included trials is generally low, further large-scale high quality trials are warranted.展开更多
A sustainable and practical process is presented for the direct synthesis of sodium tanshinone IIA sulfonate(STS).Our approach was inspired by the well-established and industrially applied batch synthetic route for ST...A sustainable and practical process is presented for the direct synthesis of sodium tanshinone IIA sulfonate(STS).Our approach was inspired by the well-established and industrially applied batch synthetic route for STS production.We constructed a telescoped two-step continuous flow platform.This involved a continuous tanshinone IIA sulfonation and in-line salt formation.For the setup,we constructed a 3D circular cyclone-type microreactor using femtosecond laser micromachining.Compared to the 68%yield for 2 h in batch,the two-step continuous flow had an STS yield of 90%,achieved for a total residence time of<3.0 min under optimal conditions.The proposed continuous flow method vastly simplified the operation and improved procedural safety,while significantly reducing the required acid content and wastewater production.展开更多
The calcium binding of erythrocyte membrane was determined in spontaneous hypertensiverats (SHR)and renovascular hypertensive rats (RVHR two-kidney, one-clip model) and the effect ofsodium tanshinone Ⅱ-A sulfonate(DS...The calcium binding of erythrocyte membrane was determined in spontaneous hypertensiverats (SHR)and renovascular hypertensive rats (RVHR two-kidney, one-clip model) and the effect ofsodium tanshinone Ⅱ-A sulfonate(DS-201)on the calcium binding in SHRs was investigated. Ourresults show that the basal calcium binding was reduced in SHRs (P<0.01 vs WKY),while the maximalcalcium binding was not,but both typies calcium bindings had no significant change in RVHRs.Sodiumtanshinone Ⅱ-A sulfonate (125μ mol/L)have no effect on the calcium binding of ecythrocyte membraneof SHR in vitro.These data further support the hypothesis that there is a cell membrane abnormalitypresent in SHRs which may possibly serve as a marker genetics of in hypertension.展开更多
Danshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine (TCM) for treatment of various diseases. Tanshinone IIA (TSA) is one of the main active components of Danshen, w...Danshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine (TCM) for treatment of various diseases. Tanshinone IIA (TSA) is one of the main active components of Danshen, which has multiple bioactivities. This article reviews the research progress of TSA in the treatment of cardiovascular disease, anti-inflammatory and immune, anti-tumor, liver protection, neuroprotection. It provides more ideas for the clinical application of TSA and the development of drug resistance.展开更多
Objective: To observe the effects of sodium tanshinone ⅡA sulfonate (STS) on angiotensin Ⅱ (Ang Ⅱ)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulate...Objective: To observe the effects of sodium tanshinone ⅡA sulfonate (STS) on angiotensin Ⅱ (Ang Ⅱ)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Methods: In the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling. Results: (1) The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ (1 μ mol/L) for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang Ⅱ and the syntheses of protein. (2) After pretreatment of myocardial cells with Ang Ⅱ (1 μmol/L) for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses (2, 10, 50μmol/L) for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang Ⅱ in a dose-dependent manner. (3) After the myocardial cells were stimulated by AngⅡ (1 μ mol/L), the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang Ⅱ was blocked distinctly by STS. (Conclusion: STS inhibited the myocardial cell hypertrophy induced by Ang Ⅱ, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.展开更多
基金a grant from National Natural Sciences Foundation of China (No. 30500657)
文摘The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (AngⅡ)-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate (STS) in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction (RT-PCR). It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly (P〈0.01). After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group (P〈0.01). After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group (P〈0.05). After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ (P〈0.05 or P〈0.01). It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.
基金Supported by the National Natural Science Foundation of China(No.81473547 and No.81673829)
文摘Objective: To systematically evaluate the effectiveness and safety of Sodium Tanshinone ⅡA Sulfonate Injection(STS) as one adjuvant therapy for treating unstable angina pectoris(UAP). Methods: Randomized controlled trials(RCTs) of UAP treated by STS were searched in the China National Knowledge Infrastructure Database(CNKI), VIP Database for Chinese Technical Periodicals(VIP), Wanfang Database, the Chinese Biomedical Literature Database(CBM), Web of Science, the Cochrane Library, Embase, and Pub Med, which from inception to January, 2016. The Cochrane Risk Assessment Tool was used to evaluate the methodological quality of the RCTs. The Review Manager 5.3 software was used to conduct the metaanalysis. Results: The results showed that 17 RCTs involving 1,372 patients were included. The meta-analysis indicated that the combined use of STS and Western medicine(WM) in the treatment of UAP can obviously improve the total effective rate [risk ratio(RR)=1.31, 95% confidence interval(CI)(1.24,1.39), P〈0.0001], and the total effective rate of electrocardiogram [RR=1.43, 95% CI(1.30,1.56), P〈0.0001], decrease the level of CRP [mean difference(MD)=–3.06, 95%CI(–3.85, –2.27), P〈0.00001], fibrinogen [MD=–1.03, 95% CI(–1.16, –0.89), P〈0.00001], and whole blood high shear viscosity [MD=–0.70, 95% CI(–0.92, –0.49), P〈0.00001]. Additionally, the occurrence of adverse drug reaction of the experimental group was significantly higher than that of the control group [RR=3.57, 95% CI(1.28, 9.94), P〈0.05]. Conclusions: Compared with WM, the combined use of STS was more effective.
基金supported by a grant from Natural Sciences Foundation of Hubei Province,China (No. 2009CDB371)
文摘To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture(CLP).Rats were randomly divided into 3 groups:sham operated group(S),sepsis group(CLP) and STS treatment group(STS).STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay(ELISA).The expression of intercellular adhesion molecule-1(ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB(NF-κB) and tissue factor(TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP(P0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α(P0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.
基金Supported by Project of Administration of Traditional Chinese Medicine of Guangdong Province Clinical Study of the Effect of TanshinoneⅡA Sodium Sulfonate on Coronary Microcirculation in Patients with Acute Coronary Syndrome(No. 20181126)Project of Special Clinical Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine Clinical Study of the Effect of TanshinoneⅡA Sodium Sulfonate on Coronary Microcirculation in Patients with Acute Coronary Syndrome (No.YN2018QL06)Project of Department of Education of Guangdong Province Acute Myocardial Infarction Chinese Medicine Prevention and Treatment Team (No. 2020KT1207)。
文摘OBJECTIVE: To investigate the efficacy and safety of Sodium tanshinone ⅡA sulfonate(STS) plus the conventional treatment on acute myocardial infarction(AMI) patients.METHODS: We searched several electrical databases and hand searched several Chinese medical journals up to January 2019. Randomized controlled trials(RCTs) comparing STS plus conventional treatment with conventional treatment were retrieved.Study screening, data extraction, quality assessment, and data analysis were conducted in accordance with the Cochrane standards.RESULTS: Sixteen trials involving 1383 people were included. The Meta-analysis showed STS combined with conventional treatment was a better treatment option than conventional treatment alone in reducing the risk of mortality, heart failure, arrhythmia and shock. In addition, STS was associated with improvement in left ventricular ejection fraction(LVEF) and left ventricular end diastolic dimension(LVEDD). No significant difference of STS was found on recurrent angina and recurrent AMI. However,the safety of STS remained uncertain for limited data.CONCLUSION: Compared with conventional treatment alone, STS combined with conventional treatment may provide more benefits for patients with AMI. Due to the fact that the overall quality of all included trials is generally low, further large-scale high quality trials are warranted.
基金the National Natural Science Foundation of China(No.22278087)。
文摘A sustainable and practical process is presented for the direct synthesis of sodium tanshinone IIA sulfonate(STS).Our approach was inspired by the well-established and industrially applied batch synthetic route for STS production.We constructed a telescoped two-step continuous flow platform.This involved a continuous tanshinone IIA sulfonation and in-line salt formation.For the setup,we constructed a 3D circular cyclone-type microreactor using femtosecond laser micromachining.Compared to the 68%yield for 2 h in batch,the two-step continuous flow had an STS yield of 90%,achieved for a total residence time of<3.0 min under optimal conditions.The proposed continuous flow method vastly simplified the operation and improved procedural safety,while significantly reducing the required acid content and wastewater production.
文摘The calcium binding of erythrocyte membrane was determined in spontaneous hypertensiverats (SHR)and renovascular hypertensive rats (RVHR two-kidney, one-clip model) and the effect ofsodium tanshinone Ⅱ-A sulfonate(DS-201)on the calcium binding in SHRs was investigated. Ourresults show that the basal calcium binding was reduced in SHRs (P<0.01 vs WKY),while the maximalcalcium binding was not,but both typies calcium bindings had no significant change in RVHRs.Sodiumtanshinone Ⅱ-A sulfonate (125μ mol/L)have no effect on the calcium binding of ecythrocyte membraneof SHR in vitro.These data further support the hypothesis that there is a cell membrane abnormalitypresent in SHRs which may possibly serve as a marker genetics of in hypertension.
文摘Danshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine (TCM) for treatment of various diseases. Tanshinone IIA (TSA) is one of the main active components of Danshen, which has multiple bioactivities. This article reviews the research progress of TSA in the treatment of cardiovascular disease, anti-inflammatory and immune, anti-tumor, liver protection, neuroprotection. It provides more ideas for the clinical application of TSA and the development of drug resistance.
文摘Objective: To observe the effects of sodium tanshinone ⅡA sulfonate (STS) on angiotensin Ⅱ (Ang Ⅱ)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Methods: In the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling. Results: (1) The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ (1 μ mol/L) for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang Ⅱ and the syntheses of protein. (2) After pretreatment of myocardial cells with Ang Ⅱ (1 μmol/L) for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses (2, 10, 50μmol/L) for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang Ⅱ in a dose-dependent manner. (3) After the myocardial cells were stimulated by AngⅡ (1 μ mol/L), the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang Ⅱ was blocked distinctly by STS. (Conclusion: STS inhibited the myocardial cell hypertrophy induced by Ang Ⅱ, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.