20(S)-ginsenoside Rg3, a neuroprotective agent, inhibits mitochondrial permeability transition pores in rat brain

Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a well-known traditional Chinese herbal medicine. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main active ingredients of ginseng. 20(S)-Ginsenoside Rg3, a triterpene glycoside which chemically belongs to the protopanaxadiol ginsenoside group, is effective in attenuating brain infarction after cerebral ischemia, but the detailed mechanism is not known. This study examined the effect of 20(S)-ginsenoside Rg3 on mitochondrial permeability transition pore (MPTP) in the rat brain. 20(S)-Ginsenoside Rg3 at 2-16 microm inhibited Ca(2+)- and H(2)O(2)-induced swelling of mitochondria isolated from rat brains. The addition of Ca(2+) generated reactive oxygen species (ROS) in isolated mitochondria. 20(S)-Ginsenoside Rg3 (2-16 microm) inhibited Ca(2+) induced generation of ROS. At the same time, 20(S)-ginsenoside Rg3 significantly improved mitochondrial energy metabolism, enhanced ATP levels and the respiratory control ratio. These results suggest that 20(S)-ginsenoside Rg3 inhibits the opening of MPTP by free radical scavenging action in the brain, and this implies that inhibition of MPTP may contribute to the neuroprotective effect of 20(S)-ginsenoside Rg3.