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槐定碱化合物通过ROS/CaMKII途径产生的抗心律失常和抗氧化作用的多方面潜力。

Multi-faceted potential of sophoridine compound's anti-arrhythmic and antioxidant effects through ROS/CaMKII pathway.

作者信息

Sun Shuai, Shi Fangdi, Zhao Gang, Zhang Hong

机构信息

Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, 030001, China.

出版信息

Heliyon. 2024 Sep 6;10(18):e37542. doi: 10.1016/j.heliyon.2024.e37542. eCollection 2024 Sep 30.

DOI:10.1016/j.heliyon.2024.e37542
PMID:39347430
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11437953/
Abstract

Cardiac arrhythmias remain a significant cause of mortality and morbidity, for novel antiarrhythmic therapies. This study states that the first report of sophoridine (SPN), a quinolizidine alkaloid derived from traditional Chinese herbs, shows promise as a potential candidate due to its anti-arrhythmic and antioxidant properties. The study found that cell viability in H9C2 rat cardiomyocytes remained stable even when treated with SPN at a higher dosage of 100 μg/ml. This phenomenon was accompanied by increases in mitochondria-derived reactive oxygen species (ROS) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, at 50 and 100 μg/ml. Glucose fluctuations regulate ventricular arrhythmias caused by SPN by activating the ROS/CaMKII pathway. Experimental models using zebrafish provided additional evidence supporting the regulatory effects of SPN on heart rate. In addition, the administration of SPN resulted in substantial deregulation of crucial genes involved in heart development (nppa, nppb, tnnt2a) at the transcriptional level in zebrafish. These findings provide insight into the various pharmacological properties of SPN and this opens up new possibilities for anti-arrhythmic treatment strategies.

摘要

心律失常仍然是导致死亡率和发病率的一个重要原因，因此需要新的抗心律失常疗法。本研究表明，槐定碱（SPN）是一种从传统中药中提取的喹诺里西啶生物碱，其首次报告显示，由于其抗心律失常和抗氧化特性，有望成为一种潜在的候选药物。研究发现，即使在100μg/ml的较高剂量下用SPN处理，H9C2大鼠心肌细胞的细胞活力仍保持稳定。在50和100μg/ml时，这种现象伴随着线粒体衍生的活性氧（ROS）和钙/钙调蛋白依赖性蛋白激酶II（CaMKII）信号的增加。葡萄糖波动通过激活ROS/CaMKII途径调节SPN引起的室性心律失常。使用斑马鱼的实验模型提供了额外的证据，支持SPN对心率的调节作用。此外，在斑马鱼中，SPN的给药导致参与心脏发育的关键基因（nppa、nppb、tnnt2a）在转录水平上发生大量失调。这些发现为SPN的各种药理特性提供了见解，并为抗心律失常治疗策略开辟了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/22b185d08cda/gr9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/22b185d08cda/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/216f5fe17e64/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/d5308f476775/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/eeb6011d3576/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/07d381b737e6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/4faebd87847f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/89d139863468/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/271733184c68/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/f5ddf127dff4/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/fd5866683951/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f1/11437953/22b185d08cda/gr9.jpg

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