Isoliensinine Eliminates Afterdepolarizations Through Inhibiting Late Sodium Current and L-Type Calcium Current

Liu, Zhi-Pei; Hu, Long; Zhang, Zefu; Song, Lv; Zhang, Peihua; Cao, Zhijun; Ma, Jing

doi:10.1007/s12012-020-09597-z

Cited by 14 publications

(5 citation statements)

References 40 publications

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“…Isoliensinine also had an inhibitory effect on stretch arrhythmias, and this effect was also achieved by blocking the ion channels activated by stretch (Chen et al, 2006). Moreover, Liu et al (Liu et al, 2020) showed that isoliensinine eliminated afterdepolarizations by inhibiting late sodium current (I NaL ) and L-type calcium current (I CaL ). The late sodium current is caused by the slow inactivation of some sodium channels after a large number of sodium channels are rapidly inactivated and is considered a target of new antiarrhythmic drugs (Antzelevitch et al, 2014).…”

Section: Anti-arrhythmiamentioning

confidence: 99%

Isoliensinine: A Natural Compound with “Drug-Like” Potential

Cheng

Zhou

et al. 2021

Front. Pharmacol.

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Isoliensinine, a bisbenzylisoquinoline alkaloid isolated from Nelumbo nucifera Gaertn, exerts a variety of beneficial effects, such as antitumor, cardioprotective, antioxidant, antidepressant, and anti-HIV effects, and ameliorates T2DM with hyperlipidemia and Alzheimer’s disease. In this article, the recent literature on isoliensinine, including its pharmacology, pharmacokinetics, and synthesis and extraction, is summarized. Moreover, possible future prospects and research directions are also discussed. Studies on isoliensinine were found by searching a combination of keywords including “pharmacology,” “pharmacokinetics,” and “synthesis and extraction” in the main databases, including PubMed, Google Scholar, Web of Science, NCBI, and Wan Fang. Many studies have pointed out that a major limitation of isoliensinine is its poor solubility in aqueous media. Considering its advantages and limitations, isoliensinine can be used as a lead compound to develop novel efficient and low-toxicity derivatives. The available literature indicates that isoliensinine displays “drug-like” potential. Additionally, there are many related issues and novel mechanisms that need to be explored.

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Section: Anti-arrhythmiamentioning

confidence: 99%

Isoliensinine: A Natural Compound with “Drug-Like” Potential

Cheng

Zhou

et al. 2021

Front. Pharmacol.

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“…The currents of the HCN4 channel were measured utilizing the whole-cell patch-clamp approach in a manner that has been previously described [ 27 , 28 ]. BMSCs were detached using trypsin and subcultured onto glass coverslips for a minimum of 30 minutes prior to patch clamping.…”

Section: Methodsmentioning

confidence: 99%

Effect of Shenfu Injection on Differentiation of Bone Marrow Mesenchymal Stem Cells into Pacemaker-Like Cells and Improvement of Pacing Function of Sinoatrial Node

Chen

Kang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Sick sinus syndrome (SSS), a complex type of cardiac arrhythmia, is a major health threat to humans. Shenfu injection (SFI), a formula of traditional Chinese medicine (TCM), is effective in improving bradyarrhythmia. However, the underlying mechanism of SFI’s therapeutic effect is subject to few systematic investigations. The purpose of the present research is to examine whether SFI can boost the differentiation effectiveness of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells and whether the transplantation of these cells can improve the pacing function of the sinoatrial node (SAN) in a rabbit model of SSS. BMSCs from New Zealand rabbits were extracted, followed by incubation in vitro. The flow cytometry was utilized to identify the expression of CD29, CD44, CD90, and CD105 surface markers. The isolated BMSCs were treated with SFI, and the whole-cell patch-clamp method was performed to detect hyperpolarization-the activated cyclic nucleotide-gated potassium channel 4 (HCN4) channel current activation curve. The SSS rabbit model was established using the formaldehyde wet dressing method, and BMSCs treated with SFI were transplanted into the SAN of the SSS rabbit model. We detected changes in the body-surface electrocardiogram and recorded dynamic heart rate measurements. Furthermore, transplanted SFI-treated BMSCs were subjected to HE staining, TUNEL staining, qPCR, western blotting, immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay to study their characteristics. Our results indicate that the transplantation of SFI-treated BMSCs into the SAN of SSS rabbits improved the pacing function of the SAN. In vitro data showed that SFI induced the proliferation of BMSCs, promoted their differentiation capacity into pacemaker-like cells, and increased the HCN4 expression in BMSCs. In vivo, the transplantation of SFI treated-BMSCs preserved the function of SAN in SSS rabbits, improved the expression of the HCN4 gene and gap junction proteins (Cx43 and Cx45), and significantly upregulated the expression of cAMP in the SAN, compared to the SSS model group. In summary, the present research demonstrated that SFI might enhance the differentiation capacity of BMSCs into pacemaker-like cells, hence offering a novel approach for the development of biological pacemakers. Additionally, we confirmed the effectiveness and safety of pacemaker-like cells differentiated from BMSCs in improving the pacing function of the SAN.

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“…Patch-Clamp Techniques. Calcium currents were recorded using whole-cell voltage-clamp techniques, as previously reported [23,24]. Currents were digitized at a sampling rate of 5 kHz.…”

Section: Simultaneous Detection Of Hipsc-cm Contraction Andmentioning

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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Isoliensinine Eliminates Afterdepolarizations Through Inhibiting Late Sodium Current and L-Type Calcium Current

Cited by 14 publications

References 40 publications

Isoliensinine: A Natural Compound with “Drug-Like” Potential

Isoliensinine: A Natural Compound with “Drug-Like” Potential

Effect of Shenfu Injection on Differentiation of Bone Marrow Mesenchymal Stem Cells into Pacemaker-Like Cells and Improvement of Pacing Function of Sinoatrial Node

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

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