Ginkgolide B induces apoptosis and developmental injury in mouse embryonic stem cells and blastocysts.
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.


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.
Chan
Wen-Hsiung
WH
Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan. whchan@cycu.edu.tw
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D015151:Immunoblotting; D007783:Lactones / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D013480:Superovulation
D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C045856:ginkgolide B; D020782:Matrix Metalloproteinases