Interaction of the Ginseng Compounds 20(S)protopanaxadiol and Rh2 with Voltage-gated Sodium Channels in Mammalian Brain

Bioactive components of ginseng have been found to be responsible for inducing multiple pharmacological responses, including changes to nervous system function. This investigation examined the interaction of 20(S)protopanaxadiol (PPD) and its monoglucoside Rh2 with voltage-gated sodium channels. These compounds inhibited [3H]batrachotoxinin A 20-α-benzoate binding to sodium channels, by targeting a locus that is allosterically coupled to neurotoxin binding site 2. Further studies on sodium channel-dependent functions revealed that these ginseng natural products also blocked veratridine-evoked depolarization of the nerve as measured by a voltage-sensitive fluoroprobe, and inhibited release of the neurotransmitters L-glutamate, GABA and L-aspartate from the nerve ending. This research clarified the mechanism by which PPD and Rh2 inhibit voltage-gated sodium channels from a biochemical standpoint. Reduced ability of the nerve to respond to a depolarizing stimulus and inhibition of neurotransmitter release may underly some of the depressant effects reported for ginsenosides on the nervous system.