Sodium Tanshinone IIA Sulfonate Research Articles

Efficacy of combined use of octreotide and sodium tanshinone IIA sulfonate in patients with cirrhosis complicated with severe acute pancreatitis

Purpose: To assess the prognosis of liver cirrhosis complicated with severe acute pancreatitis (SAP) after treatment with octreotide in combination with sodium tanshinone IIA sulfonate. Methods: A total of 164 patients with cirrhosis complicated with SAP were randomly assigned to two groups, each with 82 patients. Serum levels of inflammatory factors, as well as vascular endothelial function and liver function indices were determined. Treatment outcomes in the patients were recorded in terms of abdominal pain relief time, gastrointestinal function recovery time, hospital stay duration, and incidence of complications. Results: Relative to the control group, there were decreases in concentrations of inflammatory indices in the study cohort. Endothelial function index levels increased in the two groups, but the levels of endothelin (ET) and von Willebrand Factor (vWF) decreased more in the study group of patients, when compared to the control group, while nitric oxide (NO) level was raised (p < 0.05). Liver function improved in both groups. There were marked reductions in serum ALT, AST and total bilirubin (TBIL) in study cohort, relative to the control cohort (p < 0.05). However, albumin (ALB) levels were comparable in the two groups. Abdominal pain relief time, duration of hospitalization and time taken for normal digestive system function were shorter in the study cohort (p < 005). Receiver operating characteristic (ROC) curve analysis revealed that after treatment with octreotide and sodium tanshinone IIA sulfonate, values of area under the curve (AUC) for abdominal pain relief time, gastrointestinal function recovery time and hospital stay were 0.886, 0.918 and 0.794, respectively. Conclusion: The combined use of octreotide and sodium tanshinone IIA sulfonate inhibits the release of inflammatory factors in cirrhotic patients with SAP, and improves vascular endothelial and liver functions, thereby improving disease prognosis. These data constitute a good scientific basis for the use of octreotide and sodium tanshinone IIA sulfonate in the treatment of liver cirrhosis complicated with SAP.

Pulmonary fibrosis insights and therapy targets from disease models and administration of the lipophilic diterpene, sodium tanshinone IIA sulfonate: Review and meta-analysis.

Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p<0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-β1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.

Comparative effectiveness and safety of four traditional Chinese medicine injections with invigorating blood circulation, equivalent effect of anticoagulation or antiplatelet in acute myocardial infarction: a Bayesian network meta-analysis.

Background: Traditional Chinese medicine injections with invigorating blood circulation (TCMI-IBCs), which have been used as antithrombosis therapies, are widely employed by Chinese clinicians as adjuvant therapy for acute myocardial infarction (AMI). Objective: A Bayesian network meta-analysis was conducted to contrast the effectiveness and safety of four TCMI-IBCs in AMI. Methods: Eight Databases were thoroughly searched before 31 December 2023, for randomized controlled trials (RCTs) focusing on the application of TCMI-IBCs combined with conventional treatments (CT) to treat AMI. All-cause mortality (ACM) was the major endpoint. Secondary outcomes included bleeding events, malignant arrhythmia (MA), recurrent myocardial infarction (RMI), left ventricular ejection fraction (LVEF), and adverse events. Stata17.0 and GeMTC software were employed for Bayesian network meta-analysis. Results: A total of 73 eligible RCTs involving 7,504 patients were enrolled. Puerarin injection (PI), Danhong injection (DI), sodium Tanshinone IIA Sulfonate injection (STSI), and Danshen Chuanxiongqin injection (DCI) combined with CT can significantly reduce the occurrence of ACM and improve LVEF in AMI (P < 0.05), while without significant impact on bleeding events or MA (P > 0.05). STSI + CT would be the optimal treatment strategy in lowering RMI and ACM. DI + CT was the most likely to be the optimal strategy in reducing MA occurrence and improving LVEF. CT was likely the most effective strategy in reducing bleeding events. However, DI + CT exhibited the least favorable safety. Conclusion: TCMI-IBCs + CT had potential benefits in the treatment of AMI. STSI + CT showed the most favorable performance in treating AMI, followed by DI combined with CT. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384067, identifier CRD42022384067.

Sodium Tanshinone IIA Sulfonate Protects Primary Cardiomyocytes Against Radiation-Induced Myocardial Injury via the p38 Pathway.

Sodium tanshinone IIA sulfonate (STS), which is extracted from a Chinese medicinal herb, possesses many pharmacologic functions, such as coronary dilation, anti-inflammatory properties, and antiapoptotic and antioxidant effects. It remains unknown whether STS can protect cardiomyocytes injured after radiation therapy. An in vitro Sprague-Dawley (SD) rat neonatal cardiomyocyte system was established. Primary cardiomyocytes (PCMs) from neonatal SD rats were isolated under sterile conditions. PCM cells were divided into a control group (0 Gy/hour) and 5 experimental radiation therapy groups (0.25 Gy/hour, 0.5 Gy/hour, 1 Gy/hour, 2 Gy/hour, and 4 Gy/hour). Cell viability, the content of malondialdehyde (MDA), the lactate dehydrogenase (LDH) leakage rate, and superoxide dismutase (SOD) and glutathione (GSH) activities were recorded separately in each group after 7 days of culture. Western blot was used to detect the levels of p38, caspase-3 protein, and X protein (BAX) associated with B-cell lymphoma 2 (Bcl-2) in PCMs. X-rays inhibited cell growth, decreased cell viability, and induced an oxidative stress response in PCMs. STS and SB203580 (the inhibitor of P38 mitogen-activated protein kinase pathway) alleviated X-ray-induced damage to PCMs. An enzyme-linked immunosorbent assay showed that X-rays increased the cTnT level. STS and SB203580 ameliorated the X-ray-induced increase in cTnT leakage. X-rays enhanced the expression of p38/p-p38 and caspase-3 while reducing the expression of Bcl-2/BAX in PCMs, as demonstrated by western blotting. STS and SB203580 mitigated the changes in protein expression triggered by X-ray radiation. In conclusions, STS was shown to exert significant cardioprotective, anti-inflammatory, and antioxidant effects in PCMs by inhibiting the p38 mitogen-activated protein kinase pathway.

Sodium Tanshinone IIA Sulfonate alleviates vascular senescence in diabetic mice by modulating the A20-NFκB-NLRP3 inflammasome-catalase pathway

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence β-Galactosidase Staining (SA-β-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-β-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.

Effects of tanshinone IIA on endothelial cell dysfunction in uremic condition.

An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in uremic patients, yet its dysfunction poses a significant clinical challenge. Venous stenosis, primarily caused by venous neointimal hyperplasia, is a key factor in the failure of vascular access. During vascular access dysfunction, endothelial cells (ECs) transform mechanical stimuli into intracellular signals and interact with vascular smooth muscle cells. Tanshinone IIA, an important compound derived from Salvia miltiorrhiza, has been widely used to treat cardiovascular diseases. However, its role in modulating ECs under uremic conditions remains incompletely understood. In this research, ECs were exposed to sodium tanshinone IIA sulfonate (STS) and subjected to shear stress and uremic conditions. The results indicate that STS can reduce the suppressive effects on the expression of NF-κB p65, JNK and Collagen I in uremia-induced ECs. Moreover, the downregulation of NF-κB p65, JNK and Collagen I can be enhanced through the inhibition of ERK1/2 and the upregulation of Caveolin-1. These findings suggest that tanshinone IIA may improve EC function under uremic conditions by targeting the Caveolin-1/ERK1/2 pathway, presenting tanshinone IIA as a potential therapeutic agent against AVF immaturity caused by EC dysfunction.

Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway

BackgroundHyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia.MethodsIn this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation.ResultsOur findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression.ConclusionsThese results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

A systematic review and meta-analysis on sodium tanshinone IIA sulfonate injection for the adjunctive therapy of pulmonary heart disease

AimsSodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study.MethodsRandomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed.Results19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001).ConclusionSTS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.

Sodium tanshinone IIA sulfonate suppresses microglia polarization and neuroinflammation possibly via regulating miR-125b-5p/STAT3 axis to ameliorate neuropathic pain

The spinal cord microglia play a pivotal role in neuroinflammation and neuropathic pain (NP). Sodium tanshinone IIA sulfonate (STS), a derivative of tanshinone IIA, has anti-inflammatory and anti-hyperalgesic effects. However, its underlying mechanism in NP remains unclear. This study aimed to investigate the effect of STS and elucidate possible mechanisms in a rat model of spared nerve injury. In vivo experiments, STS and AG490 were administered intraperitoneally once daily for 14 consecutive days after surgery. The results showed that the expression of miR-125b-5p in the spinal dorsal horn was substantially reduced, whereas signal transducer and activator of transcription 3 (STAT3) signaling was increased. After treatment with STS, the mechanical thresholds, expression of miR-125b-5p, and microglial M2 marker such as Arg-1 in the spinal cord horn increased significantly, whereas multiple pro-inflammatory cytokines and apoptosis were significantly reduced. Moreover, STAT3 pathway-related proteins and expression of the microglial M1 marker, CD68, were appreciably inhibited. In vitro, lipopolysaccharide (LPS) was used to induce an inflammatory response in BV-2 microglial cells. STS pretreatment inhibited LPS-stimulated pro-inflammatory cytokine secretion, reduced STAT3 pathway related-proteins and apoptosis, increased miR-125b-5p and proopiomelanocortin expression, and enhanced microglia transformation from M1 to M2 phenotype in BV-2 cells. These effects were reversed after the inhibition of miR-125b-5p expression in BV-2 cells. A dual-luciferase reporter assay confirmed that STAT3 binds to miR-125b-5p. In summary, these results suggest that STS exerts anti-hyperalgesic and anti-neuroinflammatory effects in rats with NP possibly via the miR-125b-5p/STAT3 axis.

Effectiveness and safety of Danshen injections in treatment of cardiac failure: a network meta-analysis.

Objective: The purpose of this network meta-analysis (NMA) was to compare the therapeutic effects of various Danshen (Salvia miltiorrhiza Bunge [Lamiaceae; Salviae miltiorrhizae radix et rhizoma]) injections on heart failure to determine the optimal Danshen injection combined with conventional treatment. Methods: 8 databases were searched from the inception of these databases to May 2023 to collect randomized controlled trials (RCTs) on the effectiveness and safety of Danshen injections in the treatment of heart failure. This NMA was performed using Stata 16.0 software and R 4.1.3 software. Results: A total of 24 RCTs involving 2,186 subjects were included. The intervention group received Danshen injections plus conventional treatment, involving the following 7 Danshen injections. The results of the NMA showed that Compound Danshen injection + Common (SUCRA: 79.6%) and Sodium tanshinone ⅡA sulfonate injection + Common (SUCRA: 78.0%) exhibited higher total effective rates. Sodium tanshinone ⅡA sulfonate injection + Common (SUCRA: 94.3%) and Danshen injection + Common (SUCRA: 68.2%) were superior to other traditional Chinese medicines in improving left ventricular ejection fraction (LVEF). Danshen injection + Common (SUCRA: 99.9%) and Shenxiong glucose injection + Common (SUCRA: 77.2%) were the most effective in reducing brain natriuretic peptide (BNP). In addition, compared with conventional treatment, all Danshen injections did not increase the risk of adverse reactions. Conclusion: Current evidence shows that all seven Danshen injections are effective for heart failure. Due to the limited quantity and quality of the included studies, our findings need to be verified by more high-quality studies.

Sodium tanshinone IIA sulfonate inhibits tumor growth via miR-138 upregulation in intermittent hypoxia-induced xenograft mice.

We studied the functions of sodium tanshinone IIA sulfonate (TSA) in inducing tumor growth in obstructive sleep apnea (OSA)-mimicking intermittent hypoxia (IH) xenograft mice and the underlying potential molecular mechanism. RNA sequencing was conducted to screen the differentially expressed microRNAs in cell lines exposed to IH with or without TSA treatment. As part of the 5-week in vivo study, we treated xenograft mice with 8-h IH once daily. TSA and miR-138 inhibitors or mimics were administrated appropriately. In addition, we performed real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), microvessel density (MVD), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. RNA sequencing and RT-PCR results demonstrated that TSA increased the levels of miR-138 under IH conditions in vitro. TSA reduced the IH-stimulated high levels of hypoxia-induced factor-1α and vascular endothelial growth factor. Furthermore, IH contributed to high tumor migration, invasion, MVD, and low apoptosis. TSA attenuated IH-mediated tumor proliferation, migration, invasion, MVD, and increased apoptosis, whereas miR-138 inhibitor interrupted the effect of TSA on treating IH-induced tumor behaviors. OSA mimicking IH facilitates tumor growth and reduces miR-138 levels. TSA inhibits IH-induced tumor growth by upregulating the expression of miR-138.

Tanshinone IIA: a Chinese herbal ingredient for the treatment of atherosclerosis.

Tanshinone IIA (Tan IIA) is a fat-soluble compound extracted from Salvia miltiorrhiza, which has a protective effect against atherosclerosis (AS). Tan IIA can inhibit oxidative stress and inflammatory damage of vascular endothelial cells (VECs) and improve endothelial cell dysfunction. Tan IIA also has a good protective effect on vascular smooth muscle cells (VSMCs). It can reduce vascular stenosis by inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs), and improve the stability of the fibrous cap of atherosclerotic plaque by inhibiting apoptosis and inflammation of VSMCs. In addition, Tan IIA inhibits the inflammatory response of macrophages and the formation of foam cells in atherosclerotic plaques. In summary, Tan IIA improves AS through a complex pathway. We propose to further study the specific molecular targets of Tan IIA using systems biology methods, so as to fundamentally elucidate the mechanism of Tan IIA. It is worth mentioning that there is a lack of high-quality evidence-based medical data on Tan IIA treatment of AS. We recommend that a randomized controlled clinical trial be conducted to evaluate the exact efficacy of Tan IIA in improving AS. Finally, sodium tanshinone IIA sulfonate (STS) can cause adverse drug reactions in some patients, which needs our attention.

Evidence quality assessment of sodium tanshinone IIA sulfonate injection intervention coronary heart disease angina pectoris: An overview of systematic reviews and meta-analyses.

Sodium tanshinone IIA sulfonate injection (STS) is widely used in the clinical treatment of coronary heart disease angina pectoris (CHDAP). This article systematically summarizes and evaluates the available evidence for STS in the treatment of AP, and assess its quality. Two researchers searched and extracted 8 databases for systematic reviews (SRs)/meta-analyses (MAs), and independently assessed the methodological quality, risk of bias, reporting quality, and quality of evidence of SRs/MAs included in randomized controlled trials (RCTs). Tools used included the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the risk of bias in systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This overview includes 11 SRs/MAs that use quantitative calculations to comprehensively evaluate various efficacies of STS in AP intervention. The methodological quality, reporting quality, risk of bias, and quality of evidence for outcome measures of SRs/MAs were all unsatisfactory. All SRs/MAs are of low quality according to the results of the AMSTAR-2 assessment, and only a small number of SRs/MAs were assessed as low risk of bias based on the results of the ROBIS assessment, and none of the SRs/MAs has been fully reported on the checklist. According to GRADE system, 33 outcomes were extracted from the included SRs/MAs for evaluation, of which 12 were rated as moderate-quality evidence, 7 as low-quality evidence, and 14 as very low-quality evidence. Limitations included the lack of essential items such as protocol registration, screening of duplicate studies, provision of a list of excluded studies and assessment of publication bias. Tanshinone IIA Sulfonate Sodium Injection may be an effective and safe treatment method. However, further standardized, comprehensive SRs/MAs and RCTs are needed to provide evidence-based medical support.

Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice

BackgroundEndothelial progenitor cells (EPCs) transplantation is one of the effective therapies for neointima associated with endothelial injury. Diabetes impairs the function of EPCs and cumbers neointima prevention of EPC transplantation with an ambiguous mechanism. Sodium Tanshinone IIA Sulfonate (STS) is an endothelium-protective drug but whether STS protects EPCs in diabetes is still unknown.MethodsEPCs were treated with High Glucose (HG), STS, and Nucleotide-binding Domain-(NOD) like Receptor 3 (NLRP3), caspase-1, the Receptor of Advanced Glycation End products (AGEs) (RAGE) inhibitors, Thioredoxin-Interacting Protein (TXNIP) siRNA, and EPC proliferation, differentiation functions, and senescence were detected. The treated EPCs were transplanted into db/db mice with the wire-injured Common Carotid Artery (CCA), and the CD31 expression and neointima were detected in the CCA inner wall.ResultsWe found that STS inhibited HG-induced expression of NLRP3, the production of active caspase-1 (p20) and mature IL-1β, the expression of catalase (CAT) cleavage, γ-H2AX, and p21 in EPCs. STS restored the expression of Ki67, CD31 and von Willebrand Factor (vWF) in EPCs; AGEs were found in the HG-treated EPCs supernatant, and RAGE blocking inhibited the expression of TXNIP and the production of p20, which was mimicked by STS. STS recovered the expression of CD31 in the wire-injured CCA inner wall and the prevention of neointima in diabetic mice with EPCs transplantation.ConclusionSTS inhibits the aggravated neointima hyperplasia by protecting the proliferation and differentiation functions of EPC and inhibiting EPC senescence in diabetic mice. The mechanism is related to the preservation of CAT activity by inhibiting the RAGE-TXNIP-NLRP3 inflammasome pathway.

The efficacy and safety of sodium tanshinone ⅡA sulfonate injection in the treatment of unstable angina pectoris: A systematic review and meta-analysis.

To systematically evaluate the efficacy and safety of Sodium tanshinone ⅡA sulfonate injection (STS) in the treatment of unstable angina pectoris (UAP). CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Web of Science, Embase were searched by computer. The research covers the clinical randomized controlled trials of STS in the treatment of unstable angina pectoris published from the establishment of the library to January 31, 2023. Two researchers independently screened the literature, extracted data and evaluated the risk of research bias, and then conducted meta-analysis with RevMan5.3 software. A total of 37 randomized controlled trials were included, involving 3926 patients in total. Meta analysis results showed that, compared with conventional western medicine alone, STS combined with conventional western medicine could reduce the frequency (SMD = -2.61, 95%CI[-4.27, -0.96], P = 0.002) and duration (SMD = -4.01, 95%CI[-6.18, -1.84], P = 0.0003) of angina pectoris, improve ECG efficacy (OR = 3.61, 95%CI[2.79, 4.68], P<0.00001) and clinical symptom efficacy (OR = 4.02, 95%CI[3.32, 4.87], P<0.00001), reduce TG(SMD = -0.60, 95%CI[-1.04, -0.16], P = 0.008), TC(SMD = -3.86, 95%CI[-6.37, -1.34], P = 0.003), and LDL-C(SMD = -1.54, 95%CI[-2.67, -0.42], P = 0.007), decrease plasma viscosity(SMD = -1.02, 95%CI[-1.58, -0.47], P<0.0003), whole blood low shear viscosity(SMD = -0.85, 95%CI[-1.21, -0.49], P<0.00001), whole blood high shear viscosity(SMD = -0.82, 95%CI[-1.44, -0.20], P = 0.009), and erythrocyte aggregation index(SMD = -1.00, 95%CI[-1.75, -0.25], P = 0.009), and bring down CRP(SMD = -1.39, 95%CI[-1.91, -0.86], P<0.00001). The incidence of adverse reactions in the treatment group was higher than that in the control group (OR = 2.26, 95%CI[1.06, 4.85], P = 0.04). Neither of the two groups suffered from abnormal liver and kidney function during the study process. STS combined with routine treatment has a definite clinical efficacy and certain safety in the treatment of UAP, but it needs to be further confirmed by high-quality and low-bias randomized controlled trials in the future.

Sodium Tanshinone IIA Sulfonate Ameliorates Oxygen-glucose Deprivation/Reoxygenation-induced Neuronal Injury via Protection of Mitochondria and Promotion of Autophagy.

Sodium tanshinone IIA sulfonate (STS) has shown significant clinical therapeutic effects in cerebral ischemic stroke (CIS), but the molecular mechanisms of neuroprotection remain partially known. The purpose of this study was to explore whether STS plays a protective role in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by regulating microglia autophagy and inflammatory activity. Co-cultured microglia and neurons were subjected to OGD/R injury, an in vitro model of ischemia/reperfusion (I/R) injury with or without STS treatment. Expression of protein phosphatase 2A (PP2A) and autophagy-associated proteins Beclin 1, autophagy related 5 (ATG5), and p62 in microglia was determined by Western blotting. Autophagic flux in microglia was observed with confocal laser scanning microscopy. Neuronal apoptosis was measured by flow cytometric and TUNEL assays. Neuronal mitochondrial function was determined via assessments of reactive oxygen species generation and mitochondrial membrane potential integrity. STS treatment markedly induced PP2A expression in microglia. Forced overexpression of PP2A increased levels of Beclin 1 and ATG5, decreased the p62 protein level, and induced autophagic flux. Silencing of PP2A or administration of 3-methyladenine inhibited autophagy and decreased the production of anti-inflammatory factors (IL-10, TGF-β and BDNF) and induced the release of proinflammatory cytokines (IL-1β, IL-2 and TNF-α) by STS-treated microglia, thereby inducing mitochondrial dysfunction and apoptosis of STS-treated neurons. STS exerts protection against neuron injury, and the PP2A gene plays a crucial role in improving mitochondrial function and inhibiting neuronal apoptosis by regulating autophagy and inflammation in microglia.

Effect of Sodium TanshinoneⅡA Sulfonate on Uric Acid, Sicam-1, ET-1 and FMD in Patients with Coronary Heart Disease Complicated with Hyperuricemia.

This study was to observe the effect of Sodium TanshinoneⅡA Sulfonate (ST-ⅡAS) on blood uric acid (UA), human Soluble Intercellular Adhesion Molecule-1 (sICAM-1), Endothelin-1 (ET-1) and percentage of brachial artery Flow-Mediated Dilatation (FMD) in individuals with Hyperuricemia Complicated Coronary Heart Disease (HC-CHD). The study's participants were 108 patients with HC-CHD who attended our hospital between January 2020 and June 2022. In the trial, the patients were split into two groups with 54 instances each: the general group and the observation group. The observation group received ST-IIAS therapy, while the general group received standard care. The experiment chose to observe and compare the difference of uric acid, sICAM-1, ET-1, FMD, therapeutic effectiveness and negative effects between the two groups at various times. Results showed that on the 14th day, the observation group's amounts of UA, sICAM-1, and ET-1 were inferior to the general group (P<0.05); On the 7th and 14th days, the observation group's amount of ET-1 was lower than that of the general group (P<0.05); The observation group's FMD of patients on the 14th day was inferior to the general group after treatment (P<0.05); The observation group's overall effective rate was 94.44% higher than the general group's (P<0.05); The observation group experienced fewer negative responses than the general group did (P<0.05). In conclusion, ST-ⅡAS can be used for uric acid, vascular endothelial systolic and diastolic function in patients with HC-CHD, and has better clinical efficacy and lower risk of adverse reactions.

Two-step continuous flow process of sodium tanshinone IIA sulfonate using a 3D circular cyclone-type microreactor

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.

Sodium tanshinone IIA sulfonate attenuates sepsis-associated brain injury via inhibiting NOD-like receptor 3/caspase-1/gasdermin D-mediated pyroptosis

Sodium tanshinone IIA sulfonate (STS) has been reported to protect organ function in sepsis. However, the attenuation of sepsis-associated brain injury and its underlying mechanisms by STS has not been established. C57BL/6 mice were used to establish the cecal ligation perforation (CLP) model, and STS was injected intraperitoneally 30min before the surgery. The BV2 cells were stimulated by lipopolysaccharide after being pre-treated with STS for 4h. The STS protective effects against brain injury and in vivo anti-neuroinflammatory effects were investigated using the 48-hour survival rate and body weight changes, brain water content, histopathological staining, immunohistochemistry, ELISA, RT-qPCR, and transmission electron microscopy. The pro-inflammatory cytokines of BV2 cells were detected by ELISA and RT-qPCR. At last, the levels of NOD-like receptor 3 (NLRP3) inflammasome activation and pyroptosis in brain tissues of the CLP model and BV2 cells were detected using western blotting. STS increased the survival rate, decreased brain water content, and improved brain pathological damage in the CLP models. STS increased the expressions of tight junction proteins ZO-1 and Claudin5 while reducing the expressions of tumor necrosis factor α (TNF-α), interleukin-1β(IL-1β), and interleukin-18 (IL-18) in the brain tissues of the CLP models. Meanwhile, STS inhibited microglial activation and M1-type polarization in vitro and in vivo. The NLRP3/caspase-1/ gasdermin D (GSDMD)-mediated pyroptosis was activated in the brain tissues of the CLP models and lipopolysaccharide (LPS)-treated BV2 cells, which was significantly inhibited by STS. The activation of NLRP3/caspase-1/GSDMD-mediated pyroptosis and subsequent secretion of proinflammatory cytokines may be the underlying mechanisms of STS against sepsis-associated brain injury and neuroinflammatory response.

Preparation and performance of random- and oriented-fiber membranes with core-shell structures via coaxial electrospinning.

The cells and tissue in the human body are orderly and directionally arranged, and constructing an ideal biomimetic extracellular matrix is still a major problem to be solved in tissue engineering. In the field of the bioresorbable vascular grafts, the long-term functional prognosis requires that cells first migrate and grow along the physiological arrangement direction of the vessel itself. Moreover, the graft is required to promote the formation of neointima and the development of the vessel walls while ensuring that the whole repair process does not form a thrombus. In this study, poly (l-lactide-co-ε-caprolactone) (PLCL) shell layers and polyethylene oxide (PEO) core layers with different microstructures and loaded with sodium tanshinone IIA sulfonate (STS) were prepared by coaxial electrospinning. The mechanical properties proved that the fiber membranes had good mechanical support, higher than that of the human aorta, as well as great suture retention strengths. The hydrophilicity of the oriented-fiber membranes was greatly improved compared with that of the random-fiber membranes. Furthermore, we investigated the biocompatibility and hemocompatibility of different functional fiber membranes, and the results showed that the oriented-fiber membranes containing sodium tanshinone IIA sulfonate had an excellent antiplatelet adhesion effect compared to other fiber membranes. Cytological analysis confirmed that the functional fiber membranes were non-cytotoxic and had significant cell proliferation capacities. The oriented-fiber membranes induced cell growth along the orientation direction. Degradation tests showed that the pH variation range had little change, the material mass was gradually reduced, and the fiber morphology was slowly destroyed. Thus, results indicated the degradation rate of the oriented-fiber graft likely is suitable for the process of new tissue regeneration, while the random-fiber graft with a low degradation rate may cause the material to reside in the tissue for too long, which would impede new tissue reconstitution. In summary, the oriented-functional-fiber membranes possessing core-shell structures with sodium tanshinone IIA sulfonate/polyethylene oxide loading could be used as tissue engineering materials for applications such as vascular grafts with good prospects, and their clinical application potential will be further explored in future research.