The proliferative and chronotropic effects of Brillantaisia nitens Lindau (Acanthaceae) extracts on pluripotent stem cells and their cardiomyocytes derivatives

• Published in: Journal of ethnopharmacology 2014-10, Vol.156, p.73-81
• Main Authors: Nembo, Erastus Nembu, Dimo, Theophile, Bopda, Orelien Sylvain Mtopi, Hescheler, Jürgen, Nguemo, Filomain
• Format: Article
• Language: English
• Subjects: Acanthaceae; Action Potentials; Animals; Brillantaisia nitens; Cardiomyocytes; Cell Differentiation; Cell Proliferation; Cell Survival; Differentiation; Dose-Response Relationship, Drug; Embryonic Stem Cells - drug effects; Medicine, African Traditional; Mice; Myocytes, Cardiac - drug effects; Plant Extracts - pharmacology; Plant Leaves; Pluripotent Stem Cells - drug effects; Stem cells
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2014.07.046

Brillantaisia nitens Lindau (Acanthaceae) leaves are commonly used in traditional medicine in Africa for the treatment of many disorders including heart diseases and malaria. In this study, we therefore evaluated the effect of the methylene chloride/methanol leaf extract of Brillantaisia nitens on the proliferation of mouse pluripotent stem cells and their cardiomyocyte derivatives. In this study, we combined two emerging technologies, pluripotent stem cell-derived cardiomyocytes and modern electrophysiology systems (impedance-based real-time) to assess the cytotoxicity of Brillantaisia nitens extract (BNE). Undifferentiated pluripotent cells and cardiomyocytes were exposed to different concentrations of BNE. Cell viability and contraction were monitored by impedance using the xCELLigence system for short- and long-term treatment whereas the excitability of single cardiomyocytes was captured by patch clamp technique after BNE acute exposure. Brillantaisia nitens extract inhibited the proliferation and increased cytotoxicity of embryonic stem cells in a concentration-dependent manner. With the increase in concentration of BNE, beating rate and the contractile amplitude of cardiomyocytes changed significantly. Spontaneous rhythmic activity of cardiomyocytes was completely suppressed after 48 and 24h exposures to relatively low (4.16mg/ml) and high (8.32mg/ml) concentrations of BNE, respectively. Moreover, acute application of 4.16mg/ml of BNE led to a significant alteration of action potential (AP) parameters such as beating frequency, amplitude and AP duration at 90% of repolarization. Brillantaisia nitens extract inhibits the proliferative capacity of pluripotent stem cells and reduces electrical activity of cardiomyocytes, confirming its depressant action on the heart. [Display omitted]