Abstract

Cardiac arrhythmia is an irregular heart rhythm that can lead to serious heart conditions and various organ disorders, and may cause sudden cardiac death. Catalpol belongs to the iridoid glycoside family and is highly abundant in Rehmannia glutinosa Libosch. The study included five groups such as group I (normal control), group II (treatment control), group III (low-dose treatment), group IV (medium-dose treatment) and group V (high-dose treatment). We investigated the therapeutic effects of catalpol on cardiac arrhythmia in human-induced pluripotent stem cells (iPSCs). Cell viability, lactate dehydrogenase (LDH) levels, lipid peroxidation, antioxidant activity, and caspase-3 and caspase-9 activities and protein levels were measured in normal control, treatment control, and treated (1, 10, and 100 µM) iPSC groups. Compared with the treatment control group, catalpol supplementation (1, 10, and 100 µM) increased iPSC cell viability by 7.5, 27.3, and 65.8%, respectively; reduced the LDH levels by 10.4, 31.3, and 75.2%, respectively; and reduced the lipid peroxidation levels by 7.7, 33.0, and 62.6%, respectively. The antioxidant levels were significantly higher in the treatment control group than in the normal control group. Catalpol (100 µM) reduced the caspase-3 and caspase-9 activities by more than 30% and increased expression of the corresponding proteins by more than 50%. These findings suggest that the naturally occurring iridoid glycoside catalpol is effective against aconitine-induced cardiac arrhythmia in iPSCs.

Highlights

  • Cardiac arrhythmia an abnormal heart rhythm caused by irregular electrical activity (Benoist et al 2012) that may lead to serious heart conditions and various organ disorders, and cause sudden cardiac death (Nattel and Harada 2014)

  • Pennacchio et al (1997) showed that iridoid glycosides were cardioactive in rats, and Bi et al (2018) found that catalpol protected against cardiac

  • Experimental groups The study included five groups: Group I, normal control, human induced pluripotent stem cells (iPSCs) incubated with dimethyl sulfoxide (DMSO) for 24 h; Group II, treatment control, human iPSCs incubated with 8 μM aconitine for 24 h; Group III, low-dose treatment, human iPSCs incubated with 8 μM aconitine and 1 μM catalpol for 24 h; Group IV, medium-dose treatment, human iPSCs incubated with 8 μM aconitine and 10 μM catalpol for 24 h; and Group V, high-dose treatment, human iPSCs incubated with 8 μM aconitine and 100 μM catalpol for 24 h

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Summary

Introduction

Cardiac arrhythmia an abnormal heart rhythm caused by irregular electrical activity (Benoist et al 2012) that may lead to serious heart conditions and various organ disorders, and cause sudden cardiac death (Nattel and Harada 2014). Antiarrhythmic agents target the ion channels in the cardiomyocyte membrane, alter conduction velocity, and repress trigger activity to stabilize irregular electrical activity (Karagueuzian and Klein 2018). Conventional therapeutic agents are effective against acute cardiac arrhythmia, they produce proarrhythmia and Catalpol is an iridoid glycoside belonging the iridoid glycoside family and is highly abundant in Rehmannia glutinosa Libosch. Hu et al (2016) reported that catalpol inhibited apoptosis in cardiac myocytes via the mitochondrial-dependent caspase pathway. Pennacchio et al (1997) showed that iridoid glycosides were cardioactive in rats, and Bi et al (2018) found that catalpol protected against cardiac Catalpol has been demonstrated to have neuroprotective, anti-apoptotic, anti-inflammatory, and anti-oxidative properties in animal and cell culture studies (Jiang et al 2015; Zheng et al 2017). Hu et al (2016) reported that catalpol inhibited apoptosis in cardiac myocytes via the mitochondrial-dependent caspase pathway. Pennacchio et al (1997) showed that iridoid glycosides were cardioactive in rats, and Bi et al (2018) found that catalpol protected against cardiac

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