Ginkgolide B induces apoptosis and developmental injury in mouse embryonic stem cells and blastocysts
1Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan. whchan@cycu.edu.tw
Background:
Ginkgolide B, the major active component of Ginkgo biloba extracts, can both stimulate and inhibit apoptotic signalling. We previously showed that ginkgolide treatment of mouse blastocysts induces apoptosis, decreases cell numbers, retards early post-implantation blastocyst development and increases early-stage blastocyst death. Here, we report more detailed examinations of the cytotoxic effects of ginkgolide B on mouse embryonic stem cells (ESCs) and blastocysts and their subsequent development in vitro and in vivo.
Methods And Results:
Using cell culture assay model, we revealed in our results that ginkgolide B treatment of ESCs (ESC-B5) induced apoptosis via reactive oxygen species (ROS) generation, c-Jun N-terminal kinase (JNK) activation, loss of mitochondrial membrane potential (MMP) and the activation of caspase-3. Furthermore, an in vitro assay model showed that ginkgolide B treatment inhibited cell proliferation and growth in mouse blastocysts. Finally, an in vivo model showed that treatment with 10 microM ginkgolide B caused resorption of post-implantation blastocysts and fetal weight loss.
Conclusions:
Our results reveal for the first time that ginkgolide B retards the proliferation and development of mouse ESCs and blastocysts in vitro and causes developmental injury in vivo.
Insights
Ginkgolide B from Ginkgo biloba harms early development. It induces apoptosis in mouse embryonic stem cells and blastocysts, hindering growth and causing developmental injury in vivo.
Area of Science:
- Developmental Biology
- Cell Biology
- Pharmacology
Background:
- Ginkgolide B, a key component of Ginkgo biloba, exhibits dual effects on apoptotic signaling.
- Previous studies indicated ginkgolide treatment induces apoptosis and impairs early mouse blastocyst development.
Purpose of the Study:
- To investigate the cytotoxic effects of ginkgolide B on mouse embryonic stem cells (ESCs) and blastocysts.
- To examine the impact of ginkgolide B on subsequent in vitro and in vivo development.
Main Methods:
- Cell culture assays were used to assess ginkgolide B's effects on ESCs (ESC-B5).
- In vitro and in vivo models were employed to evaluate blastocyst proliferation, growth, and developmental outcomes.
- Mechanisms of apoptosis, including ROS generation, JNK activation, mitochondrial membrane potential, and caspase-3 activation, were analyzed.
Main Results:
- Ginkgolide B induced apoptosis in ESCs through reactive oxygen species (ROS) generation, c-Jun N-terminal kinase (JNK) activation, loss of mitochondrial membrane potential (MMP), and caspase-3 activation.
- In vitro, ginkgolide B inhibited cell proliferation and growth in mouse blastocysts.
- In vivo, 10 microM ginkgolide B treatment led to post-implantation blastocyst resorption and fetal weight loss.
Conclusions:
- Ginkgolide B retards the proliferation and development of mouse ESCs and blastocysts in vitro.
- Ginkgolide B causes developmental injury in vivo, including blastocyst resorption and reduced fetal weight.
