Salvianolic acid B and Tanshinone IIA attenuate myocardial ischemia injury in mice by NO production through multiple pathways

Pan, Chun‐Shui; Lou, Lixia; Huo, Yingqing; Singh, Gurbakhshish; Meng, Chen; Zhang, Dongmei; Wu, Aiming; Zhao, Ming; Shuo-ren, Wang; Li, Jian

doi:10.1177/1753944710396538

Cited by 77 publications

(50 citation statements)

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“…Activation of AMPK was found to contribute to elevated [Ca 21 ] i response to hypoxia through activation of store-operated calcium entry. STS has been shown to activate AMPK at the site of Thr(172) in human umbilical vein endothelial cells (60). The roles of ROS, PKC, and AMPK and their relationship to the inhibitory effects of STS on hypoxic up-regulation of TRPC in PASMCs remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Wang

Qian

Wan

et al. 2013

Am J Respir Cell Mol Biol

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Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca 21 concentration ([Ca 21 ] i ) and store-operated Ca 21 entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn 21 quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O 2 , 21 d) was increased by 59%, and basal [Ca 21 ] i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca 21 ] i were associated with reduced expression of canonical transient receptor potential (TRPC)1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0-25 mM) dose-dependently inhibited hypoxiainduced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca 21 ] i , SOCE, mRNA, and protein expression of TRPC1 and TRPC6. STS also relieved right ventricular systolic pressure, right ventricular hypertrophy, and TRPC1 and TRPC6 protein expression in distal pulmonary arteries in a monocrotaline-induced rat model of pulmonary arterial hypertension. These results indicate that STS prevents pulmonary arterial hypertension development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca 21 ] i and attenuated proliferation and migration of PASMCs.Keywords: STS; TRPC; SOCE; pulmonary hypertension Pulmonary arterial hypertension (PAH) is a rare yet life-threatening disease that affects 15 per 1 million adults, according to the most recent estimation in 2008 (1). It is physiologically defined by mean pulmonary arterial pressure of 25 mm Hg or greater at rest and is pathologically characterized by pulmonary vascular remodeling, including smooth muscle hypertrophy and intima thickening. Although significant progress has been made in the past decades in our understanding of PAH and in disease management, the prognosis is still poor, with a 1-year survival rate of 91.0% (2) and 3-year survival rate of 77% or less according to recent investigations (3-5). The principal treatments for PAH rely on approaches targeting the prostacyclin, endothelin, or NO pathways (phosphodiesterase inhibition) or, increasingly, on a combination of them (6-11). Few patients show indication for treatment with calcium channel...

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Section: Discussionmentioning

confidence: 99%

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Wang

Qian

Wan

et al. 2013

Am J Respir Cell Mol Biol

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“…A subgroup of sham and RUPP rats were treated with STS in their drinking water (ϳ27 mg·kg Ϫ1 ·day Ϫ1 ) from the day of surgery to euthanasia. The dosage of STS was chosen following a literature review that determined treatment regimens of 80 mg/day in human (ϳ1.1 mg·kg Ϫ1 ·day Ϫ1 ) (18,19) and ovine (ϳ1.8 mg·kg Ϫ1 ·day Ϫ1 ) (23, 50) trials and a median of 20 mg·kg Ϫ1 ·day Ϫ1 in rodent studies (30,37,45,46,49,51). Systolic and diastolic blood pressures and heart rate were measured by insertion of an in-dwelling carotid catheter under isoflurane anesthesia before euthanasia on GD20.…”

Section: Methodsmentioning

confidence: 99%

“…Our own group has shown STS-induced vasodilation of mesenteric arteries from male Sprague-Dawley rats (21). We demonstrated that STS-induced vasodilation was partially mediated by endothelium-derived hyperpolarization, whereas others have shown effects of STS on NO production, either through direct modulation of eNOS (30) or through nongenomic estrogen receptor actions on eNOS (8). In addition, there have been three clinical studies that have shown positive maternal effects of STS on hypertension in pregnancy: a reduction in morbidity, mean arterial pressure, and blood viscosity, cholesterol, and lipoprotein (20,22,43).…”

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confidence: 99%

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

Morton

Quon

Cheung

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Morton JS, Quon A, Cheung PY, Sawamura T, Davidge ST. Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia. Am J Physiol Regul Integr Comp Physiol 308: R163-R172, 2015. First published December 4, 2014 doi:10.1152/ajpregu.00222.2014.-Preeclampsia is a disorder of pregnancy with a significant impact on maternal and fetal health. The complexity of this multifactorial condition has precluded development of effective therapies and, although many potential pathways have been investigated, the etiology still requires clarification. Our group has investigated the scavenger lectin-like oxidized LDL (LOX-1) receptor, which may respond to factors released from the distressed placenta that contribute to the vascular pathologies observed in preeclampsia. Given the known beneficial effects of sodium tanshinone IIA sulfonate (STS; a component of Salvia miltiorrhiza) on vasodilation, reduction of oxidative stress, and lipid profiles, we have investigated its role as a potential treatment strategy. We hypothesized that STS would improve vascular endothelial function and, combined with a reduction in oxidative stress, would improve pregnancy outcomes in a rat model of preeclampsia (reduced uteroplacental perfusion pressure, RUPP). We further hypothesized this may occur via the action of STS on the LOX-1 and/or platelet-activating factor (PAF) receptor axes. The RUPP model increased maternal blood pressure, vascular oxidative stress, and involvement of the vascular PAF receptor. Treatment with STS during pregnancy decreased both oxidative stress and involvement of the PAF receptor; however, it also increased involvement of the LOX-1 receptor, which is in line with the concept that scavenger receptors, such as LOX-1 and PAF, are upregulated in response to ligand binding and/or under pathological conditions. In this model of preeclampsia, however, the vascular actions of STS did not lead to improvements in pregnancy outcome such as fetal biometrics or maternal blood pressure. preeclampsia; pregnancy; vascular function; tanshinone; LOX-1; PAF receptor PREECLAMPSIA is a major cause of maternal and fetal morbidity and mortality affecting from 2% to 8% of pregnancies worldwide each year with developing countries impacted to a greater extent than industrialized countries (44). It is a highly complex disorder for which many pathological pathways and potential key components have been proposed. In general, poor development of placental spiral arteries is thought to cause the release of circulating factors from a poorly perfused placenta, which impair maternal vascular function, manifested as endothelial dysfunction (4, 17, 27). Impaired maternal vascular function then leads to an abnormal hemodynamic response to pregnancy and reduced perfusion of maternal organs, including the placenta, resulting in a positive feedback loop. Currently, the only known "cure" for preeclampsia is removal of the placenta, and by default the fetus, reinforcing this organ's central role in the disorder. Our own group has demonstr...

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“…In a porcine model of myocardial I/R, MLB increased capillary density and decreased infarct size [51] . In C57 mice, MLB was found to inhibit cardiac hypertrophy and infarction and to improve cardiac function at 4 weeks after induction of the infarction [44] . In rats with left anterior descending coronary artery ligation, MLB treatment effectively improved left ventricle (LV) function and the appearance of the myocardium as compared with a group with acute myocardial infarction (AMI) [52,53] ; MLB treatment also prevented myocardial remodeling, a deleterious consequence of myocardial infarction (MI), by significantly down-regulating the mRNA expression level and activity of MMP-9 [52] .…”

Section: Protecting Against Myocardial Ischemia and Reperfusion (I/r)mentioning

confidence: 93%

“…MLB could also inhibit Ca 2+ influx and decrease NO release in ECs exposed to hypoxia and attenuate cell injury in ECs [43] . In HUVECs, MLB enhanced NO production via the AMPK/ PI3K/Akt pathway [44] . MLB was also found to produce endothelium-dependent vasodilation by regulating NO production through the modulation of heme oxygenase-1 and arginase activities [41] .…”

Section: Preventing Endothelial Dysfunctionmentioning

confidence: 96%

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

Wang

2012

Acta Pharmacol Sin

108

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Salvia miltiorrhiza, a traditional medical herb known as danshen, has been widely used in China to improve blood circulation, relieve blood stasis, and treat coronary heart disease. S miltiorrhiza depside salt is a novel drug recently developed at the Shanghai Institute of Materia Medica; it contains magnesium lithospermate B (MLB) and its analogs, rosmarinic acid (RA) and lithospermic acid (LA), as active components. The drug has been used in the clinic to improve blood circulation and treat coronary heart disease. The pharmacological effects of the depside salt from S miltiorrhiza and its components have been extensively investigated. Experimental studies have demonstrated that magnesium lithospermate B possesses a variety of biological activities, especially protective effects in the cardiovascular system such as attenuation of atherosclerosis and protection against myocardial ischemia-reperfusion injury. Rosmarinic acid and lithospermic acid also show beneficial effects on the cardiovascular system. This paper reviews the recent findings regarding the mechanisms underlying the pharmacological actions of the active components of S miltiorrhiza depside salt, based on published works and our own observations.

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Salvianolic acid B and Tanshinone IIA attenuate myocardial ischemia injury in mice by NO production through multiple pathways

Abstract: These findings suggest that both Sal B and Tan IIA have cardioprotective function in certain levels through multiple targets related with NO production, such as eNOS phosphorylation, L-arginine uptake and CAT expression, which may have major clinical implications.

Cited by 77 publications

References 22 publications

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

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