Sodium tanshinone IIA sulfonate: A review of pharmacological activity and pharmacokinetics

Zhou, Zhong-Yan; Zhao, Wai-Rong; Zhang, Jing; Chen, Xinlin; Tang, Jingyi

doi:10.1016/j.biopha.2019.109362

Cited by 73 publications

(60 citation statements)

References 103 publications

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“…As one of the major biologically active constituents in Danshen, Tan IIA has been successfully used for coronary heart diseases, cerebrovascular diseases, and myocardial infarction treatment in the clinic. 9,30,31 In the past decades, Tan IIA has attracted great interest in cancer prevention and chemotherapy due to its significant antitumor efficacy and minimal side effects. Recent reports revealed that Tan IIA inhibits NSCLC cells via down-regulating the PI3K/Akt signalling 32 and activating the JNK pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>Inhibition of EGFR Signaling and Activation of Mitochondrial Apoptosis Contribute to Tanshinone IIA-Mediated Tumor Suppression in Non-Small Cell Lung Cancer Cells</p>

Gao

Liu

et al. 2020

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Background: Deregulation of epidermal growth factor receptor (EGFR) signaling plays a critical role in non-small cell lung cancer (NSCLC) tumorigenesis. The natural product Tanshinone IIA (Tan IIA) exhibits significant anti-tumor effect in various human cancers, however, the mechanism remains elusive. Methods: The inhibitory effect of Tan IIA NSCLC cells was determined by MTS and soft agar assays. The activation of EGFR signaling and the protein level of myeloid cell leukemia 1 (Mcl-1) were examined by immunoblot (IB), immunohistochemical staining (IHC), and ubiquitination analysis. The in vivo anti-tumor effect was validated by the xenograft mouse model. Results: Tan IIA inhibits NSCLC cells through suppression of EGFR signaling. Tan IIA decreases cell viability and colony formation in EGFR wild type and activating mutant cell lines. The IB data further confirmed that Tan IIA suppresses EGFR phosphorylation timeand dose-dependently. Tan IIA destabilizes Mcl-1 and shortens the half-life. Ubiquitination analysis showed that treatment with Tan IIA promotes Mcl-1 ubiquitination and degradation. Further study showed that the downregulation of EGFR-Akt signaling is required for Tan IIA-induced Mcl-1 reduction. Ectopic overexpression of constitutively activated Akt1 compromised these antitumor efficacies in Tan IIA-treated NSCLC cells. Finally, Tan IIA inhibited the in vivo tumor growth. Conclusion: Our data indicate that Tan IIA acts as an EGFR signaling inhibitor, and targeting EGFR-Akt-Mcl1 axis could provide a new option for NSCLC treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Inhibition of EGFR Signaling and Activation of Mitochondrial Apoptosis Contribute to Tanshinone IIA-Mediated Tumor Suppression in Non-Small Cell Lung Cancer Cells</p>

Gao

Liu

et al. 2020

OTT

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“…Zebrafish disease models have the advantages of low cost, ease of observation, and genetic similarity with humans, which facilitates drug discovery ( Dooley and Zon, 2000 ; Kari et al, 2007 ; Delvecchio et al, 2011 ). In our group, we have established various zebrafish disease models, including neuroprotection ( Chong et al, 2013 ; Chong et al, 2014 ), angiogenesis ( Zhou et al, 2017 ; Zhou et al, 2019b ; Zhou et al, 2020 ), cerebral hemorrhage ( Huang et al, 2018 ; Zhou et al, 2019c ), etc., for bioactive constitutes discovery from natural products and underlying mechanisms studies. Thus, zebrafish-based cerebral hemorrhage model attracted our attention for high-throughput screening of drugs for hemorrhage stroke ( Hung et al, 2012 ; Crilly et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, the rescue effect of STS along with downregulated hif1al2 expression was only partially attenuated by Akt and ERK inhibitors ( Figures 5C, D ), in opposite to what is expected based on the results in Liang et al (2018) . STS promoted vascular endothelial function and cell survival through Akt/eNOS and MAPKs signaling pathways ( Zhou et al, 2019c ). Thus, the activation of Akt/MAPKs signaling pathways might be important in the maintenance of vascular integrity and permeability by STS in cerebral hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

“…STS injection has been approved by the China State Food and Drug Administration (CFDA) for the treatment of cardiovascular diseases, including coronary heart disease, myocardial infarction, and angina ( Yang et al, 2009 ). Recent studies indicated that STS exerts multiple pharmacological activities and could also have the potential for management of ischemia stroke, cardiac hypertrophy, and pulmonary hypertension ( Takahashi et al, 2002 ; Wang et al, 2013 ; Ji et al, 2017 ; Zhou et al, 2019c ). In our previous study ( Zhou et al, 2018 ), STS significantly decreased both the hemorrhage rate and area in zebrafish in a dose-dependent manner, while STS did not cause toxicity up in zebrafish to 300 µM ( Figure 1C ).…”

Section: Introductionmentioning

confidence: 99%

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Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

et al. 2020

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Hemorrhage stroke is a severe vascular disease of the brain with a high mortality rate in humans. Salvia miltiorrhiza Bunge (Danshen) is a well-known Chinese Materia Medica for treating cerebral vascular and cardiovascular diseases in traditional Chinese medicine. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, which is the main active ingredient of Danshen. In our previous study, we established a zebrafish model of cerebral hemorrhage and found that STS dramatically decreased both the hemorrhage rate and hemorrhage area, although the underlying mechanism was not fully elucidated. We conducted a transcriptome analysis of the protective effect of STS against atorvastatin (Ator)-induced cerebral hemorrhage in zebrafish using RNA-seq technology. RNA-seq revealed 207 DEGs between the Ator-treated group and control group; the expression levels of 53 DEGs between the Ator-treated group and control group were reversed between the STS + Ator-treated group and Ator-treated group. GO enrichment analysis indicated that these 53 DEGs encode proteins with roles in hemoglobin complexes, oxygen carrier activity and oxygen binding, etc. KEGG analysis suggested that these 53 DEGs were most enriched in three items, namely, porphyrin and chlorophyll metabolism, ferroptosis, and the HIF-1 signaling pathway. The PPI network analysis identified 12 hub genes, and we further verified that Ator elevated the mRNA expression levels of hemoglobin ( hbae1.3 , hbae3 , hbae5, hbbe2 , and hbbe3 ), carbonic anhydrase ( cahz) , HIF-1 ( hif1al2 ) and Na+/H+ exchanger ( slc4a1a and slc9a1 ) genes, while STS significantly suppressed these genes. In addition, we found that pharmacological inhibition of PI3K/Akt, MAPKs, and mTOR signaling pathways by specific inhibitors partially attenuated the protective effect of STS against Ator-induced cerebral hemorrhage in zebrafish, regardless of mTOR inhibition. We concluded that hemoglobin, carbonic anhydrase, Na+/H+ exchanger and HIF-1 genes might be potential biomarkers of Ator-induced cerebral hemorrhage in zebrafish, as well as pharmacological targets of STS. Moreover, HIF-1 and its regulators, i.e., the PI3K/Akt and MAPK signaling pathways, were involved in the protective effect of STS against Ator-induced cerebral hemorrhage. This study also provided evidence of biomarkers involved in hemorrhage stroke and improved understanding of the effects of HMG-COA reductase inhibition on vascular permeability and cerebral hemorrhage.

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“…NaAsO2 is the most toxic, affecting people in many countries around the world, including China.Arsenic has been shown to cause many cardiovascular diseases and to cause cardiomyocyte damage and cardiomyocyte apoptosis 5,6) .Sodium tanshinone IIA sulfonate (STS) has been approved by China Food and Drug Administration (CFDA) for the treatment of cardiovascular disease. 7,8) However, the combination of NaAsO2 poisoning and STS has not been reported. The effect of STS on myocardial injury induced by NaAsO2 was investigated at the cellular level.The results of CCK-8 Assay showed that A certain concentration of STS (0-50 and 100umol / l) had no cytotoxic effect on H9C2 cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sodium tanshinone IIA sulfonate on H9C2 cardiomyocyte injury induced by sodium arsenite

Zhang¹,

Li²,

Sheng³

et al. 2020

Preprint

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Arsenic is a grade I human carcinogen that can cause kinds of damage to the body.The heart is one of the main target organs of arsenic damage,but the preventive and curative measures underlying arsenic poisoning are not clear. To investigate the effect of tanshinone IIA sulfonate (STS) on the injury of H9C2 cardiomyocytes induced by NaAsO2,H9C2 cardiomyocyteswere divided into four groups where control group with general medium,arsenic (As) group received sodium arsenite (NaAsO2)-containing general medium,STS pretreatment+As group and finally the STS alone group . Compared with the control group, different concentrations of STS had no significant effect on the cell viability (n = 6, P > 0.05); Compared with the control group, there was no significant change in the viability of cells treated with arsenic for 12 h after STS pretreatment for 6 h (n = 6, P > 0.05),the viability of cells treated with NaAsO2 alone was decreased(n = 6, P < 0.05);Compared with the control group, the cell viability was decreased after STS pretreatment for 12h and arsenic for 24h,the cell viability of NaAsO2 group was also decreased,the viability of NaAsO2 cells was lower than that of STS pretreated for 12h with NaAsO2 for 24h(n=6,p<0.05).The content of Caspase 3/7 in the NaAsO2 group was higher than that in the STS and NaAsO2 group and the Control group and STS group after 12h,the differences were statistically significant(n=6,p<0.05).After STS pretreatment for 12h and NaAsO2 for 24 h, there was no significant difference in Caspase 8 content between NaAsO2 group and other groups (n=6,P>0.05) As a result,Sodium tanshinone IIA sulfonate can attenuate the injury of H9C2 cardiomyocytes induced by sodium arsenite.

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Sodium tanshinone IIA sulfonate: A review of pharmacological activity and pharmacokinetics

Cited by 73 publications

References 103 publications

<p>Inhibition of EGFR Signaling and Activation of Mitochondrial Apoptosis Contribute to Tanshinone IIA-Mediated Tumor Suppression in Non-Small Cell Lung Cancer Cells</p>

<p>Inhibition of EGFR Signaling and Activation of Mitochondrial Apoptosis Contribute to Tanshinone IIA-Mediated Tumor Suppression in Non-Small Cell Lung Cancer Cells</p>

Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

Effects of Sodium tanshinone IIA sulfonate on H9C2 cardiomyocyte injury induced by sodium arsenite

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