Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes
Traditional Chinese medicine injection (TCMI) refers to the use of modern technology to make Chinese patent medicines in injectable forms, which shorten the onset time of the traditional Chinese medicine (TCM). Although there have been clinical cases in which Shenmai injection (SMI) was used to trea...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580822002072 |
| _version_ | 1811167254284337152 |
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| author | Zhang Zhang Yuxin Li Meihui Yan Tingting Yu Xin Yuan Sen Li |
| author_facet | Zhang Zhang Yuxin Li Meihui Yan Tingting Yu Xin Yuan Sen Li |
| author_sort | Zhang Zhang |
| collection | DOAJ |
| description | Traditional Chinese medicine injection (TCMI) refers to the use of modern technology to make Chinese patent medicines in injectable forms, which shorten the onset time of the traditional Chinese medicine (TCM). Although there have been clinical cases in which Shenmai injection (SMI) was used to treat cardiovascular diseases (CVDs), there are no pharmacological experiments that investigate the efficacy of the drug in vitro or the underlying mechanisms. Aim of the study: We aimed to systemically evaluate the efficacy and investigate the mechanisms of SMI in modulating electrophysiology and calcium (Ca2+) signaling using a microelectrode array (MEA) and a genetically encoded Ca2+ indicator, GCaMP6s, respectively, in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Materials and methods: A MEA system was employed to record field potentials (FPs) in hiPSC-CMs. The QT interval is corrected by the RR interval, the reciprocal of the beating rate. GCaMP6s was used to measure Ca2+ signaling in hiPSC-CMs. Meanwhile, the transcriptome changes in hiPSC-CMs treated with 2% SMI were examined using RNAseq. In addition, the ingredients of SMI were investigated using liquid chromatography-mass spectrometry (LC-MS). Results: It was found that 0.5%, 1%, and 2% (v/v) SMIs could increase corrected QT (QTc) but did not change other FP parameters. GCaMP6s was successfully applied to measure the chronic function of SMI. The full width at half maximum (FWHM), rise time, and decay time significantly decreased after treatment with SMI for 1 h and 24 h, whereas an increased Ca2+ transient frequency was observed. Conclusions: We first used the Ca2+ indicator to measure the chronic effects of TCM. We found that SMI treatment can modulate electrophysiology and calcium signaling and regulate oxidative phosphorylation, cardiac muscle contraction, and the cell cycle pathway in hiPSC-CMs. |
| first_indexed | 2024-04-10T16:07:21Z |
| format | Article |
| id | doaj.art-a1384ddf1c6946c483c4949c5fe3a4fc |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-04-10T16:07:21Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-a1384ddf1c6946c483c4949c5fe3a4fc2023-02-10T04:22:44ZengElsevierBiochemistry and Biophysics Reports2405-58082023-03-0133101407Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytesZhang Zhang0Yuxin Li1Meihui Yan2Tingting Yu3Xin Yuan4Sen Li5School of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaCorresponding author.; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaTraditional Chinese medicine injection (TCMI) refers to the use of modern technology to make Chinese patent medicines in injectable forms, which shorten the onset time of the traditional Chinese medicine (TCM). Although there have been clinical cases in which Shenmai injection (SMI) was used to treat cardiovascular diseases (CVDs), there are no pharmacological experiments that investigate the efficacy of the drug in vitro or the underlying mechanisms. Aim of the study: We aimed to systemically evaluate the efficacy and investigate the mechanisms of SMI in modulating electrophysiology and calcium (Ca2+) signaling using a microelectrode array (MEA) and a genetically encoded Ca2+ indicator, GCaMP6s, respectively, in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Materials and methods: A MEA system was employed to record field potentials (FPs) in hiPSC-CMs. The QT interval is corrected by the RR interval, the reciprocal of the beating rate. GCaMP6s was used to measure Ca2+ signaling in hiPSC-CMs. Meanwhile, the transcriptome changes in hiPSC-CMs treated with 2% SMI were examined using RNAseq. In addition, the ingredients of SMI were investigated using liquid chromatography-mass spectrometry (LC-MS). Results: It was found that 0.5%, 1%, and 2% (v/v) SMIs could increase corrected QT (QTc) but did not change other FP parameters. GCaMP6s was successfully applied to measure the chronic function of SMI. The full width at half maximum (FWHM), rise time, and decay time significantly decreased after treatment with SMI for 1 h and 24 h, whereas an increased Ca2+ transient frequency was observed. Conclusions: We first used the Ca2+ indicator to measure the chronic effects of TCM. We found that SMI treatment can modulate electrophysiology and calcium signaling and regulate oxidative phosphorylation, cardiac muscle contraction, and the cell cycle pathway in hiPSC-CMs.http://www.sciencedirect.com/science/article/pii/S2405580822002072Calcium indicatorshiPSC-CMsShenmai injectionTraditional Chinese medicine |
| spellingShingle | Zhang Zhang Yuxin Li Meihui Yan Tingting Yu Xin Yuan Sen Li Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes Biochemistry and Biophysics Reports Calcium indicators hiPSC-CMs Shenmai injection Traditional Chinese medicine |
| title | Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes |
| title_full | Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes |
| title_fullStr | Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes |
| title_full_unstemmed | Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes |
| title_short | Investigating the effect of Shenmai injection on cardiac electrophysiology and calcium signaling using human-induced pluripotent stem cell-derived cardiomyocytes |
| title_sort | investigating the effect of shenmai injection on cardiac electrophysiology and calcium signaling using human induced pluripotent stem cell derived cardiomyocytes |
| topic | Calcium indicators hiPSC-CMs Shenmai injection Traditional Chinese medicine |
| url | http://www.sciencedirect.com/science/article/pii/S2405580822002072 |
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