Synergistic protective effect of astragaloside IV–tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia

Yang, Jiehong; Li, Jinhui; Lü, Jing; Zhang, Yuyan; Zhu, Ziling; Wan, Haitong

doi:10.1016/j.jep.2011.12.023

Cited by 54 publications

(49 citation statements)

References 34 publications

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“…AS-IV, as one of its active elements, has been revealed its pharmacological mechanisms to some degree. Recent researches have suggested that AS-IV might protect from cardiomyopathy via diverse effects upon a variety of intracellular signaling pathways, including the activation of Src/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, 22) inhibiting tumor growth factor (TGF)-β1 23) and ERK1/2 signaling pathways, 24) upregulating superoxide dismutase-1 levels, 3,25) antioxidative and nitric oxide-inducing pathway, 26) and improving intracellular calcium handling. 27,28) The aim of our study is to clarify the basic electrophysiological effects of AS-IV on cardiac myocytes, and we have found that AS-IV prolonged APd, and decreased I K and I CaL in guinea-pig cardiac myocytes.…”

Section: Effects Of As-iv On Na + Currentsmentioning

confidence: 99%

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Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

Zhao

et al. 2013

Biological & Pharmaceutical Bulletin

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Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1×10 −6 m, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1±38.9 to 785.3±83.7 ms. AS-IV at 1×10 −6 m also enhanced the inward rectifier K + currents (I K1 ) and inhibited the delayed rectifier K + currents (I K ). AS-IV (1×10 −6 m) strongly depressed the peak of voltage-dependent Ca 2+ channel current (I CaL ) from −607.3±37.5 to −321.1±38.3 pA. However, AS-IV was not found to affect the Na + currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I K . AS-IV also influences Ca 2+ signaling through suppressing I CaL .

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Section: Effects Of As-iv On Na + Currentsmentioning

confidence: 99%

“…antioxidation, [3][4][5] antivirus, 6,7) anti-apoptosis, 8,9) anti-hyperglycemic, 10,11) neuroprotection, 13) gastroprotection, 14) anti-chronicasthma, 15) and anti-lung-cancer. 16) One of AS-IV's targets is the cardiovascular system, and especially the heart.…”

mentioning

confidence: 99%

Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

Zhao

et al. 2013

Biological & Pharmaceutical Bulletin

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“…For decades, it has been widely used to treat cardiovascular and cerebrovascular diseases (Cai et al, 2000;Li et al, 2004;Chen et al, 2011;Yang et al, 2012), pulmonary hypertension (Tang et al, 1988;Jian-Sheng et al, in press), chronic renal failure (Cao et al, 1997), and cirrhosis (Li et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The effect of ligustrazine on L-type calcium current, calcium transient and contractility in rabbit ventricular myocytes

Ren

Zhang

et al. 2012

Journal of Ethnopharmacology

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“…Overwhelming evidences have accumulated implying that excessive reactive oxygen species (ROS) and oxidative stress play key roles in the pathophysiology of I/R injury [13]. Normally, there is a balance between the formation of ROS and its consumption by the endogenous protective systems.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Total Steroid Saponins on Cerebral Ischemia Injuries in an Animal Model of Focal Ischemia/Reperfusion

et al. 2014

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Total steroid saponins (TSSN) isolated from Dioscorea zingiberensis C.H.Wright (DZW), a unique Traditional Chinese Medicine, is known for its potential usage in various types of diseases. However, there are a little evidences about its neuroprotective effect in transient focal ischemia-reperfusion (I/R) cerebral injury. Therefore, the current study was carried out to investigate the effect of TSSN on neuroprotection and its potential mechanisms in the rat I/R model by middle cerebral artery occlusion (MCAO) for 90 min. The rats were each treated with TSSN (30 mg/kg, 10 mg/kg, and 3 mg/kg) or Nimodipine (20 mg/kg) daily for 6 days before MCAO. Then, the neurological deficit score, cerebral infarct volume, and brain water content were measured at 24 h after reperfusion. Meanwhile, the histopathological changes and AQP-4 protein activities were examined in hippocampal CA1 and the cortex of ipsilateral ischemic cerebral hemisphere by hematoxylin & eosin staining and immunohistochemistry, respectively. The indices of oxidative stress in the serum were also obtained, and NF-κB and ERK 1/2 protein expressions in the injured brain were evaluated by western blotting. The results indicated that the pre-treatment with these drugs not only significantly reduced cerebral infarct volume, brain water content and improved neurological deficit score, but also restored neuronal morphology and decreased the AQP-4 positive cells in CA1 and the cortex. Moreover, it markedly restored the level of oxidant stress makers (CAT, SOD, MDA, NO and iNOS) to their normal range in serum. In addition, the increased NF-κB and ERK 1/2 protein expressions were alleviated as compared with the I/R group. These findings demonstrate that TSSN exhibits promising neuroprotection effects against the transient focal ischemia-reperfusion (I/R) cerebral injury in the rat experimental model, where the underlying mechanisms might be mediated through inhibition of anti-edema as well as anti-oxidative effects by inactivation of NF-κB and ERK 1/2 signalling pathway.

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Synergistic protective effect of astragaloside IV–tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia

Abstract: This study showed that ASG IV-TMPZ played a pivotal synergistic protective role against focal cerebral ischemic reperfusion damage in a rat experimental model.

Cited by 54 publications

References 34 publications

Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

The effect of ligustrazine on L-type calcium current, calcium transient and contractility in rabbit ventricular myocytes

Neuroprotective Effects of Total Steroid Saponins on Cerebral Ischemia Injuries in an Animal Model of Focal Ischemia/Reperfusion

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