An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-01-11

AUTHORS

Ruiying Wang, Min Wang, Shan Wang, Ke Yang, Ping Zhou, Xueheng Xie, Qi Cheng, Jingxue Ye, Guibo Sun, Xiaobo Sun

ABSTRACT

BACKGROUND: Cardiotoxicity remains an important concern in drug discovery and clinical medication. Meanwhile, Sophora tonkinensis Gapnep. (S. tonkinensis) held great value in the clinical application of traditional Chinese medicine, but cardiotoxic effects were reported, with matrine, oxymatrine, cytisine, and sophocarpine being the primary toxic components. METHODS: In this study, impedance and extracellular field potential (EFP) of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were recorded using the cardio non-labeled cell function analysis and culture system (Cardio-NLCS). The effects of matrine, oxymatrine, cytisine, and sophocarpine (2, 10, 50 μM) on cell viability; level of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (CTn-I); antioxidant activities; production of reactive oxygen species (ROS) and malondialdehyde (MDA); and disruption of intracellular calcium homeostasis were also added into the integrated assessment. RESULTS: The results showed that matrine and sophocarpine dose-dependently affected both impedance and EFP, while oxymatrine and cytisine altered impedance significantly. Our study also indicated that cardiotoxicity of matrine, oxymatrine, cytisine, and sophocarpine was related to the disruption of calcium homeostasis and oxidative stress. Four alkaloids of S. tonkinensis showed significant cardiotoxicity with dose dependence and structural cardiotoxicity synchronized with functional changes of cardiomyocytes. CONCLUSIONS: This finding may provide guidance for clinical meditation management. Furthermore, this study introduced an efficient and reliable approach, which offers alternative options for evaluating the cardiotoxicity of the listed drugs and novel drug candidates. More... »

PAGES

20

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13287-018-1126-4

DOI

http://dx.doi.org/10.1186/s13287-018-1126-4

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30635051


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28 schema:description BACKGROUND: Cardiotoxicity remains an important concern in drug discovery and clinical medication. Meanwhile, Sophora tonkinensis Gapnep. (S. tonkinensis) held great value in the clinical application of traditional Chinese medicine, but cardiotoxic effects were reported, with matrine, oxymatrine, cytisine, and sophocarpine being the primary toxic components. METHODS: In this study, impedance and extracellular field potential (EFP) of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were recorded using the cardio non-labeled cell function analysis and culture system (Cardio-NLCS). The effects of matrine, oxymatrine, cytisine, and sophocarpine (2, 10, 50 μM) on cell viability; level of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (CTn-I); antioxidant activities; production of reactive oxygen species (ROS) and malondialdehyde (MDA); and disruption of intracellular calcium homeostasis were also added into the integrated assessment. RESULTS: The results showed that matrine and sophocarpine dose-dependently affected both impedance and EFP, while oxymatrine and cytisine altered impedance significantly. Our study also indicated that cardiotoxicity of matrine, oxymatrine, cytisine, and sophocarpine was related to the disruption of calcium homeostasis and oxidative stress. Four alkaloids of S. tonkinensis showed significant cardiotoxicity with dose dependence and structural cardiotoxicity synchronized with functional changes of cardiomyocytes. CONCLUSIONS: This finding may provide guidance for clinical meditation management. Furthermore, this study introduced an efficient and reliable approach, which offers alternative options for evaluating the cardiotoxicity of the listed drugs and novel drug candidates.
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35 schema:keywords Chinese medicine
36 Gapnep
37 MB isoenzyme
38 Sophora tonkinensis Gapnep
39 activity
40 alkaloids
41 alternative option
42 analysis
43 antioxidant activity
44 applications
45 approach
46 assessment
47 calcium homeostasis
48 candidates
49 cardiac troponin I
50 cardio non-labeled cell function analysis
51 cardiomyocytes
52 cardiotoxic effects
53 cardiotoxicity
54 cardiotoxicity of matrine
55 cell function analysis
56 cell viability
57 cell-derived cardiomyocytes
58 changes
59 characterization
60 clinical applications
61 clinical medication
62 clinical meditation management
63 components
64 concern
65 creatine kinase MB isoenzyme
66 culture system
67 cytisine
68 dehydrogenase
69 dependence
70 discovery
71 disruption
72 dose
73 dose dependence
74 drug candidates
75 drug discovery
76 drugs
77 effect
78 effects of matrine
79 extracellular field potentials
80 field potentials
81 findings
82 function analysis
83 functional changes
84 great value
85 guidance
86 homeostasis
87 human pluripotent stem cell-derived cardiomyocytes
88 impedance
89 important concern
90 integrated assessment
91 integrated characterization
92 intracellular calcium homeostasis
93 isoenzymes
94 kinase MB isoenzyme
95 lactate dehydrogenase
96 levels
97 malondialdehyde
98 management
99 matrine
100 medications
101 medicine
102 meditation management
103 non-labeled cell function analysis
104 novel drug candidates
105 options
106 oxidative stress
107 oxygen species
108 oxymatrine
109 pluripotent stem cell-derived cardiomyocytes
110 potential
111 primary toxic component
112 production
113 reactive oxygen species
114 reliable approach
115 results
116 significant cardiotoxicity
117 sophocarpine
118 sophocarpine dose
119 species
120 stem cell-derived cardiomyocytes
121 stress
122 structural cardiotoxicity
123 study
124 system
125 tonkinensis
126 tonkinensis Gapnep
127 toxic components
128 traditional Chinese medicine
129 troponin I
130 values
131 viability
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