Sodium tanshinone IIA sulfonate improves adverse ventricular remodeling post MI by reducing myocardial necrosis, modulating inflammation and promoting angiogenesis

2021 ◽  
Vol 28 ◽  
Author(s):  
Baoli Zhang ◽  
Peng Yu ◽  
Enyong Su ◽  
Jianguo Jia ◽  
Chunyu Zhang ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Immunohistochemical Staining ◽  
Ventricular Remodeling ◽  
Smooth Muscle Actin ◽  
Myocardial Necrosis ◽  
Tanshinone Iia ◽  
Vascular Density ◽  
Therapeutic Effects ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Scar Size

Background and Objective: Myocardial infarction (MI) leads to pathological cardiac remodeling and heart failure. Sodium tanshinone IIA sulfonate (STS) shows therapeutic values. The present study aimed to explore the potential role of STS in ventricular remodeling post-MI Methods: Mice were randomly divided into sham, MI + normal saline (NS) and MI + STS (20.8 mg/kg/day intraperitoneally) groups. MI was established following left anterior descending artery ligation. Cardiac function was evaluated using echocardiography. Scar size and myocardial fibrosis-associated markers were detected using Masson’s trichrome staining and western blot analysis (WB). Necrosis and inflammation were assessed using H&E staining, lactate dehydrogenase (LDH) detection, ELISA, immunohistochemical staining, and WB. Furthermore, angiogenesis markers and associated proteins were detected using immunohistochemical staining and WB. Results: Mice treated with STS exhibited significant improvements in cardiac function, smaller scar size, and low expression levels of α-smooth muscle actin and collagen I and III at 28 days following surgery, compared with the NS-treated group. Moreover, treatment with STS reduced eosinophil necrosis, the infiltration of inflammatory cells, plasma levels of LDH, high mobility group protein B1, interleukin-1β and tumor necrosis factor-α, and protein expression of these cytokines at 3 days. Macrophage infiltration was also decreased in the STS group in the early phase. Additionally, CD31+ vascular density, protein levels of hypoxia-inducible factor-1α, and vascular endothelial growth factor were elevated in the STS-treated mice at 28 days. Conclusion: STS improved pathological remodeling post-MI, and the associated therapeutic effects may result from a decrease in myocardial necrosis, modulation of inflammation, and an increase in angiogenesis.

scholarly journals Sodium Tanshinone IIA Sulfonate Promotes Spinal Cord Injury Repair  by Inhibiting BSCB Disruption In Vitro and In Vivo

2020 ◽  
Author(s):  
Dan Luo ◽  
Xing Li ◽  
Jiheng Zhan ◽  
Yonghui Hou ◽  
Jiyao Luan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tanshinone Iia ◽  
Neurological Deficits ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Sodium Tanshinone Iia Sulfonate

Abstract Background:Spinal cord injury (SCI) leads to microvascular damage and the destruction of blood spinal cord barrier (BSCB), which progresses to secondary injuries like apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair the damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. We found that STS restored BSCB integrity and promoted microvessel recovery 7 days after SCI in a mouse model. However, the therapeutic effects of STS on damaged BSCB in the early stage of SCI remained uncertain. Methods: we exposed spinal cord microvascular endothelial cells (SCMECs) to H2O2 and treated them with different doses of STS. The mice received intraperitoneal injection of STS after SCI in vivo model. Spinal cord tissue was taken 1 and 3d post-SCI. HE, Nissl staining, BSCB permeability, and the expression levels of tight junction (TJ) and adherens junction (AJ), MMP2, MMP9, NeuN, and C-caspase-3 were analyzed.Results: In addition to protecting the cells from H2O2-induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI as well, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMPs activation and prevented TJ and AJ the loss of proteins. Conclusions:Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium

2011 ◽  
Vol 301 (2) ◽  
pp. H548-H554 ◽  
Author(s):  
Mitsuo Sobajima ◽  
Takashi Nozawa ◽  
Takuya Shida ◽  
Takashi Ohori ◽  
Takayuki Suzuki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Smooth Muscle Actin ◽  
Left Ventricular ◽  
Vascular Density ◽  
Peripheral Blood Flow ◽  
Mrna Levels ◽  
Cross Sectional

Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

scholarly journals Tanshinones induce tumor cell apoptosis via directly targeting FHIT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianglian Zhou ◽  
Yuting Pan ◽  
Yue Wang ◽  
Bojun Wang ◽  
Yu Yan ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Tanshinone Iia ◽  
Binding Affinities ◽  
Tumor Cell Apoptosis ◽  
Anti Cancer ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Direct Binding ◽  
Fhit Protein ◽  
Diadenosine Triphosphate

AbstractThe liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.

scholarly journals Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e51991 ◽  
Author(s):  
Eva Mathieu ◽  
Guillaume Lamirault ◽  
Claire Toquet ◽  
Pierre Lhommet ◽  
Emilie Rederstorff ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Intramyocardial Delivery

scholarly journals QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yong Wang ◽  
Chun Li ◽  
Yuli Ouyang ◽  
Tianjiao Shi ◽  
Xiaomin Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Nadph Oxidase ◽  
Caspase 3 ◽  
Ventricular Remodeling ◽  
Cardiac Injury ◽  
Myocardial Tissue ◽  
Therapeutic Effects ◽  
Histological Changes ◽  
Nadph Oxidase 4

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect.

scholarly journals Functional Recovery after Scutellarin Treatment in Transient Cerebral Ischemic Rats: A Pilot Study with18F-Fluorodeoxyglucose MicroPET

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jin-hui Li ◽  
Jing Lu ◽  
Hong Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Neurological Deficit ◽  
Neuronal Maturation ◽  
Vascular Density ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Neuronal Marker ◽  
Cerebral Ischemic

Objective. To investigate neuroprotective effects of scutellarin (Scu) in a rat model of cerebral ischemia with use of18F-fluorodeoxyglucose (18F-FDG) micro positron emission tomography (microPET).Method. Middle cerebral artery occlusion was used to establish cerebral ischemia. Rats were divided into 5 groups: sham operation, cerebral ischemia-reperfusion untreated (CIRU) group, Scu-25 group (Scu 25 mg/kg/d), Scu-50 group (Scu 50 mg/kg/d), and nimodipine (10 mg/Kg/d). The treatment groups were given for 2 weeks. The therapeutic effects in terms of cerebral infarct volume, neurological deficit scores, and cerebral glucose metabolism were evaluated. Levels of vascular density factor (vWF), glial marker (GFAP), and mature neuronal marker (NeuN) were assessed by immunohistochemistry.Results. The neurological deficit scores were significantly decreased in the Scu-50 group compared to the CIRU group (P<0.001).18F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in Scu-50 group compared with CIRU group (P<0.01) and Scu-25 group (P<0.01). Immunohistochemical analysis demonstrated Scu-50 enhanced neuronal maturation.Conclusion.18F-FDG microPET imaging demonstrated metabolic recovery after Scu-50 treatment in the rat model of cerebral ischemia. The neuroprotective effects of Scu on cerebral ischemic injury might be associated with increased regional glucose activity and neuronal maturation.

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