Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury<i>In Vivo</i>and<i>In Vitro</i>

Fan, Hui; Liu, Yang; Fu, Fenghua; Xu, Hui; Meng, Qinggang; Zhu, Haibo; Teng, Lirong; Yang, Mingyan; Zhang, Leiming; Zhang, Ziliang; Liu, Ke

doi:10.1155/2012/508938

Cited by 49 publications

(35 citation statements)

References 17 publications

(19 reference statements)

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“…The mechanisms elucidating the role of SalA in regulation of biological processes in endothelial cells, vascular smooth muscle cells, and cardiomyocytes have been investigated [25,26,27]. It has been described that SalA might be a cardiovascular protective agent during reperfusion injury, mainly through its anti-apoptosis activity via induction of Bcl-2 and inhibition of Bax [28,29]. In agreement with these data, we showed that SalA abolished suppression of Bcle-2 and enhancement of Bax induced by hypoxia (Fig.…”

Section: Discussionmentioning

confidence: 99%

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

Xie¹,

Duan

Guo³

et al. 2015

Cell Physiol Biochem

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Background: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDLr expression, ER stress, and apoptosis under hypoxia condition. Methods: Human umbilical vein endothelial cells (HUVECs) pretreated with SalA were subjected to hypoxia stimulation. Endothelial ER stress and apoptosis were examined. The mRNA levels were tested by real-time RT-PCR, and the protein levels were determined by immunoblot analysis. Results: Pretreatment of HUVECs with SalA markedly attenuated hypoxia-induced endothelial ER stress and apoptosis. Hypoxia resulted in enhancement of VLDLr expression, which was effectively inhibited by SalA pretreatment. Furthermore, luciferase reporter gene assays indicated that SalA inhibited vldlr gene promoter activity, and ChIP assays showed that hypoxia increase the recruitment of HIF-1α to the vldlr gene promoter, and this process was hampered markedly by pretreatment of SalA. Finally, overexpression of VLDLr abolished SalA-mediated protection of endothelial cells from ER stress and apoptosis. Knockdown of VLDLr mimicked SalA protective effect. Conclusion: These results for the first time demonstrate that SalA protects against hypoxia-induced endothelial ER stress and apoptosis through inhibiting recruitment of HIF-1α to vldlr gene promoter and thus suppressing VLDLr expression.

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Section: Discussionmentioning

confidence: 99%

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

Xie¹,

Duan

Guo³

et al. 2015

Cell Physiol Biochem

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“…These results showed that intravenous infusion of salvianolate peri-operatively is more beneficial for the cardiac function recovery of patients and has positive effects on improving myocardial perfusion volume and promoting the recovery of CO. Fan et al (13) also acknowledged the conclusions mentioned above in their reports, and they believed that >80% of salvianolate is salvia magnesium acetate, which can play an important role in expanding cardiovascular blood flow, inhibiting the synthesis of endothelin, and help improve myocardial ischemia and anoxia to promote a positive outcome.…”

Section: Discussionmentioning

confidence: 93%

Perioperative application of salvianolate on oxidative stress and plasma IMD/ADM2 in patients with acute myocardial infarction undergoing PCI

Zhang

Jiao

Chen

2017

Experimental and Therapeutic Medicine

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The present study was conducted to investigate the effects of salvianolate on perioperative oxidative stress and plasma Intermedin/adrenomedullin 2 (IMD/ADM2) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). The clinical data of 108 patients with AMI treated by PCI were retrospectively analyzed. According to the use of salvianolate in perioperative period, the patients were divided into the study group (n=62) and the control group (n=46). The control group was given routine treatment while the study group was given routine treatment combined with intravenous infusion of salvianolate (200 mg administered once at 24 h before operation, once/day after operation, 1 week later, the curative effect was observed). The changes in levels of hemodynamic indexes [fibrinogen (FIB), platelet aggregation rate (PAG), plasma viscosity, packed-cell volume (PCV)], oxidative stress indexes [superoxide dismutase (SOD), glutathione peroxidase (GSH Px)], cardiac function indexes [left ventricular ejection fraction (LVEF), cardiac output (CO)], related biochemical indexes [high-sensitivity C-reactive protein (hs-CRP), N-terminal pro brain natriuretic peptide (NT proBNP)] and plasma IMD/ADM2 in the two groups at 24 h pre-operation and the 8th day postoperation were analyzed. On the 8th day post-operation, hemodynamic indexes such as FIB (3.3±1.0 and 3.9±0.9) g/l, PAG (20.6±6.5 and 41.6±7.7)%, plasma viscosity (1.1±0.5 and 1.7±0.6) mPa•s/120 s−1 and PCV (40.0±3.8 and 45.5±3.7)%, the related biochemical indexes such as hs-CRP (55.1±4.8 and 79.3±5.3) mg/l and NT-proBNP (435.6±305.2 and 788.6±310.8) ng/l in the two groups were significantly decreased compared to those pre-operation; the differences were statistically significant (P<0.05). The oxidative stress indexes such as SOD (43.6±1.9 and 24.2±2.0) U/ml and GSH-Px (822.6±13.52 and 742.6±62.6) enzyme activity unit, the cardiac function indexes such as LVEF (45.1±3.5 and 41.9±3.3)% and CO (4.6±0.5 and 4.1±0.5) l/min and plasma IMD/ADM2 (163.5±20.2 and 144.2±22.5) pg/ml in the two groups were significantly increased compared to those pre-operation; the differences were statistically significant (P<0.05). In conclusion, applying intravenous infusion of salvianolate in patients with AMI during perioperative period of PCI can effectively improve the oxidative stress reaction and have positive effects on regulating plasma IMD/ADM2 level, which promoted cardiac function recovery and enhances myocardial perfusion volume.

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“…Recent research shows that Sal A has antiapoptotic effects via activating ERK1/2 and downregulating c-Jun N-terminal kinase (JNK), with increased Bcl-2 and reduced Bax protein expression [112, 113]. A combination of SalB and ginsenoside Rg1 increases the viability of cardiac myocytes and reduces infarct size, thereby improving the functional parameters of the heart against I/R injury in rats [114].…”

Section: Resultsmentioning

confidence: 99%

Oxidative Stress andSalvia miltiorrhizain Aging-Associated Cardiovascular Diseases

Chang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Aging-associated cardiovascular diseases (CVDs) have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM) has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs.

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Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion InjuryIn VivoandIn Vitro

Cited by 49 publications

References 17 publications

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

Perioperative application of salvianolate on oxidative stress and plasma IMD/ADM2 in patients with acute myocardial infarction undergoing PCI

Oxidative Stress andSalvia miltiorrhizain Aging-Associated Cardiovascular Diseases

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