Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis / 中国天然药物

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis / 中国天然药物

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

Sodium Tanshinone II A Sulfonate Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials / 中国结合医学杂志

<p><b>OBJECTIVE</b>To systematically evaluate the effectiveness and safety of Sodium Tanshinone II A Sulfonate Injection (STS) as one adjuvant therapy for treating unstable angina pectoris (UAP).</p><p><b>METHODS</b>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 PubMed, 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.</p><p><b>RESULTS</b>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].</p><p><b>CONCLUSIONS</b>Compared with WM, the combined use of STS was more effective.</p>

Effects of sodium tanshinone IIA sulfonate on TGF-β1-induced atrial fibroblasts differentiation / 中国药学杂志

OBJECTIVE: To observe the effects and mechanisms of sodium tanshinone II A sulfonate (STS) on transforming growth factor-β1 (TGF-β1)-induced atrial fibroblasts differentiation. METHODS: In the culture of neonatal rat atrial fibroblasts, type I/III collagen in the cell culture supernatant were measured by enzyme-linked immunosorbent assay. The proliferation activity was measured by methylthiazolyl tetrazolium(MTT) assay. Atrial fibroblasts differentiation was determined by measuring the expression of α-SMA(α-smooth muscle actin) using Western blot and immunofluorescence. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation was measured by Western blot. RESULTS: STS can decrease TGF-β1-induced elevations of type I/III collagen and proliferation activity; inhibit the expression of α-SMA and ERK1/2 activation. CONCLUSION: SIS can inhibit TGF-β1-induced atrial fibroblasts differentiation, the mechanism may be associated with depression of ERKl/2 signaling pathway.

Effects of sodium tanshinone II A sulfonate on Ang II-induced cardiomyocyte oxidative stress / 中国药学杂志

OBJECTIVE: To observe the effects and mechanisms of sodium tanshinone II A sulfonate (STS) on angiotensin II (Ang II)-induced cardiomyocyte oxidative stress. METHODS: In the primary culture of neonatal rat cardiomyocytes, the content of reactive oxygen species (ROS) was measured by 2, 7-dichlorofluorescein diacetate (DCFH-DA). 8-hydroxydeoxyguanosine level in the supernatant was measured by ELISA. As indexes of cardiomyocyte oxidative stress, the cellular contents of MDA and SOD, cell vialibity and LDH release were measured. NADPH oxidase (NOX) activity was measured by chromatometry. The expressions of p47phox was assessed using Western blot. RESULTS: STS can decrease Ang II-induced elevations of ROS level and oxidative stress, and inhibit the expression of p47phox and NOX activity. CONCLUSION: The inhibitory effects of STS on Ang II-induced cardiomyocyte oxidative stress may be associated with depressing NOX signaling pathway via down regulation of p47phox expression. Copyright 2012 by the Chinese Pharmaceutical Association.