Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model
Date
2018-10-05
Journal Title
Journal ISSN
Volume Title
Publisher
BMC (part of Springer Nature)
Abstract
Background: Sutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal
plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few
studies report on its toxicology and dosage in vivo. There is still room to better understand its cytotoxicity effects in
animal systems.
Methods: We prepared two extracts, one with 80% (v/v) ethanol, and the other, with water. Both were studied to
determine the maximum tolerable concentration when extracts were applied at 0 to 200 μg/ml to a Tuebingen
zebrafish embryo line. The development of zebrafish embryos after 24 h post fertilization (hpf) was studied. A
concentration range of 5 μg/ml to 50 μg/ml was then chosen to monitor the ontological development of cultured
embryos. A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was used to study
the differences of the two experimental extracts. Chemical variation between the extracts was illustrated using
chemometrics.
Results: Both extracts led to bleeding and pericardial cyst formation when applied at high concentrations to the
zebrafish embryo culture. Chronic teratogenic toxicities, leading to pericardial edema, yolk sac swelling, and other
abnormal developmental characteristics, were detected. The aqueous extracts of S. frutescens were less toxic to the
larvae than the ethanol extracts, validating preference for aqueous preparations when used in traditional medicine.
Chemical differences between the water extracts and alcoholic extracts were analysed using LC-MS/MS. A
supervised metabolomics approach, targeting the sutherlandiosides and sutherlandins using orthogonal partial least
squares-discriminant analysis (OPLS-DA), illustrated that sutherlandiosides were the main chemical features that can
be used to distinguish between the two extracts, despite the extracts being highly similar in their chemical
constituents. Conclusion: The water extract caused less cytotoxic and abnormal developmental effects compared to the
ethanolic extract, and, this is likely due to differences in concentrations of extracted chemicals rather than the
chemical profile per se. This study provides more evidence of cytotoxicity effects linked to S. frutescens using the
zebrafish embryo bioassay as a study tool.
Description
CITATION: Chen, L., et al. 2018. Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model. BMC Complementary and Alternative Medicine, 18:273, doi:10.1186/s12906-018-2303-9.
The original publication is available at https://bmccomplementalternmed.biomedcentral.com
The original publication is available at https://bmccomplementalternmed.biomedcentral.com
Keywords
Antibody-dependent cell cytotoxicity, Medicinal plants, Toxicity testing, Toxicity testing -- In vivo
Citation
Chen, L., et al. 2018. Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model. BMC Complementary and Alternative Medicine, 18:273, doi:10.1186/s12906-018-2303-9