Mechanisms underlying the cardio-protection of total ginsenosides against myocardial ischemia in rats in vivo and in vitro: Possible involvement of L-type Ca2+ channels, contractility and Ca2+ homeostasis

Han, Xue; Li, Mengying; Zhao, Zhifeng; Zhang, Yuanyuan; Zhang, Jianping; Zhang, Xuan; Zhang, Ying; Guan, Shengjiang; Chu, Li

doi:10.1016/j.jphs.2019.02.001

Cited by 21 publications

(18 citation statements)

References 57 publications

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“…The heart tissues were removed from the fixing fluid, and were then cleared, dehydrated, macerated and embedded in paraffin. The tissue samples were sectioned at 5-µm thickness and were stained with hematoxylin for 15 min and eosin for 5 min, both at room temperature according to standard procedures (46). The samples were visualized under an optical microscope at x400 magnification (Leica DM4000B; Leica Microsystems GmbH).…”

Section: Methodsmentioning

confidence: 99%

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Zhao

Zheng

et al. 2020

Mol Med Rep

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arsenic trioxide (aTo) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the u.S. Food and drug administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (crT), the critical ingredient of saffron. Sprague-dawley rats were then randomly divided into four groups (n=10/group): i) control group; ii) aTo group, iii) crT-low (20 mg/kg) group; and iv) crT-high (40 mg/kg) group. rats in the control and aTo groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and crT groups were administered with either 20 and 40 mg/kg crT. Following 6 h, all groups except the control group were intraperitoneally injected with 5 mg/kg aTo over 10 days. cardiotoxicity was indicated by changes in electrocardiographic (ecG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis-related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. cardiotoxicity was induced in male Sprague-dawley rats with aTo (5 mg/kg). crT (20 and 40 mg/kg) and aTo were co-administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J-point elevation induced by aTo in rats. Histological changes were evaluated via hematoxylin and eosin staining. crT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione-peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, crT downregulated the expression levels of the pro-inflammatory factors IL-1, TnF-α, il-6, Bax and p65, as well as increased the expression of Bcl-2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that crT treatment effectively ameliorated aTo-induced cardiotoxicity. The protective effects of crT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by aTo treatment, and additional clinical applications are possible, but warrant further investigation.

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Section: Methodsmentioning

confidence: 99%

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Zhao

Zheng

et al. 2020

Mol Med Rep

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“…The dosages and paradigms of injections were performed according to previous studies. 20 After induction of myocardial ischemia for two consecutive days, the heart was removed and used for the same experiments as the normal rat ventricular myocytes.…”

Section: Isolation Of Cardiomyocytesmentioning

confidence: 99%

<p>Cardioprotective Effect of Monoammonium Glycyrrhizinate Injection Against Myocardial Ischemic Injury in vivo and in vitro: Involvement of Inhibiting Oxidative Stress and Regulating Ca<sup>2+</sup> Homeostasis by L-Type Calcium Channels</p>

Zhao¹,

Liu²,

Zhang³

et al. 2020

DDDT

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Monoammonium glycyrrhizinate (MAG) is an aglycone of glycyrrhizin that is found in licorice and is often used clinically as an injection to treat liver diseases. However, the effect of MAG injection on cardiac function and its possible cellular mechanisms remain unclear. We explored the protective effects of MAG against myocardial ischemic injury (MII) induced by isoproterenol (ISO), as well as the cellular mechanisms via molecular biology techniques and patch-clamp recording. Methods: A rat model of myocardial ischemia injury was induced by administering ISO (85 mg/kg) subcutaneously for 2 consecutive days. ECG, cardiac functional parameters, CK and LDH levels, SOD and GSH activities, MDA concentration, histological myocardium inspection, mitochondria ultrastructure changes, intracellular calcium concentrations were observed. Influences of MAG on I Ca-L and contraction in isolated rat myocytes were observed by the patch-clamp technique. Results: MAG reduced damage, improved cardiac morphology, inhibited oxidative stress, decreased the generation of reactive oxygen species, and decreased intracellular Ca 2+ concentration. Exposure of the rats' ventricular myocytes to MAG resulted in a concentrationdependent reduction in L-type calcium currents (I Ca-L). MAG reduced I Ca-L in a consistent and time-dependent fashion with a semi-maximal prohibitive concentration of MAG of 14 μM. MAG also shifted the I-V curve of I Ca-L upwards and moved the activation and inactivation curves of I Ca-L to the left. Conclusion: The findings indicate that MAG injection exerts a protective influence on ISOinduced MII by inhibiting oxidative stress and regulating Ca 2+ homeostasis by I Ca-L .

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“…This study further analyzed the specific mechanisms underlying HSYA-mediated cardioprotection from the perspective of calcium channel regulation, aiming to advance the knowledge of HSYA as a treatment against MI/IR. Myocardial enzyme levels are important for measuring the degree of myocardial cell damage [2]. This study demonstrated that HSYA can significantly attenuate HR-induced AST, CK-MB, and LDH levels in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 64%

“…Ischemic heart disease is associated with high mortality rates and disability burden worldwide [1]. Recovery of blood circulation in the ischemic heart through therapy can cause further damage to the myocardial tissue, which is defined as myocardial ischemia/reperfusion injury (MI/RI) [2]. The mechanisms underlying MI/RI are complex and have not yet been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Myocardial ischemia/reperfusion injury (MI/RI) is an urgent problem with a great impact on health globally. However, its pathological mechanisms have not been fully elucidated. Hydroxysafflor yellow A (HSYA) has a protective effect against MI/RI. This study is aimed at further clarifying the relationship between HSYA cardioprotection and calcium overload as well as the underlying mechanisms. We verified the protective effect of HSYA on neonatal rat primary cardiomyocytes (NPCMs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from hypoxia-reoxygenation (HR) injury. To explore the cardioprotective mechanism of HSYA, we employed calcium fluorescence, TUNEL assay, JC-1 staining, and western blotting. Finally, cardio-ECR and patch-clamp experiments were used to explain the regulation of L-type calcium channels (LTCC) in cardioprotection mediated by HSYA. The results showed that HSYA reduced the levels of myocardial enzymes and protected NPCMs from HR injury. HSYA also restored the contractile function of hiPSC-CMs and field potential signal abnormalities caused by HR and exerted a protective effect on cardiac function. Further, we demonstrated that HSYA protects cardiomyocytes from HR injury by decreasing mitochondrial membrane potential and inhibiting apoptosis and calcium overload. Patch-clamp results revealed that MI/RI caused a sharp increase in calcium currents, which was inhibited by pretreatment with HSYA. Furthermore, we found that HSYA restored contraction amplitude, beat rate, and field potential duration of hiPSC-CMs, which were disrupted by the LTCC agonist Bay-K8644. Patch-clamp experiments also showed that HSYA inhibits Bay-K8644-induced calcium current, with an effect similar to that of the LTCC inhibitor nisoldipine. Therefore, our data suggest that HSYA targets LTCC to inhibit calcium overload and apoptosis of cardiomyocytes, thereby exerting a cardioprotective effect and reducing MI/RI injury.

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Mechanisms underlying the cardio-protection of total ginsenosides against myocardial ischemia in rats in vivo and in vitro: Possible involvement of L-type Ca2+ channels, contractility and Ca2+ homeostasis

Cited by 21 publications

References 57 publications

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

<p>Cardioprotective Effect of Monoammonium Glycyrrhizinate Injection Against Myocardial Ischemic Injury in vivo and in vitro: Involvement of Inhibiting Oxidative Stress and Regulating Ca<sup>2+</sup> Homeostasis by L-Type Calcium Channels</p>

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis

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