  Radix Bupleuri is a hepatoprotective traditional Chinese medicine (TCM) used
for thousands of years in clinical, which was reported to be linked with liver
damage. Previous studies have revealed that saikosaponins are the major types
of components that contribute to the hepatotoxicity of Radix Bupleuri. However
the underlying molecular mechanism is far from being understood. In order to
clarify whether these structural analogues exert toxicity effects through the
same molecular targets, a systematic comparison study was done in this paper.
The effects of SSa, b2, c, and d on isolated rat liver mitochondria and human
hepatocyte L02 cells were explored, respectively. The collective results
indicated that although saikosaponins share the similar structures but they
have quite different mechanisms. SSb2 and SSd showed most serious damage on the
function of mitochondria and survival rate of cell, respectively. SSb2 could
cause mitochondrial permeability transition pore (mPTP) opening and collapse of
mitochondrial membrane potential ({\Delta}{\Psi}m) by impairing the
mitochondrial respiratory chain complex III. While SSd destroyed plasma
membrane and led to the release of lactate dehydrogenase (LDH) mainly through
activating caspase-1. Furthermore, the combine index (CI) demonstrated that the
combined hepatotoxicity of SSb2 and SSd could be additive. This finding might
yield more in depth understanding of hepatotoxicity of Radix Bupleuri possess
many different saikosaponins.
