Figure 5.

A schematic illustration on cytosolic Ca²⁺ overload signalings and ginsenoside-mediated attenuation against cytosolic Ca²⁺ overload. This schematic drawing shows that cytosolic Ca²⁺ levels could be elevated in ischemic or traumatic brain injury. The elevation of cytosolic Ca²⁺ levels occurs either via direct activation of voltage-gated Ca²⁺ channels or via depolarization caused by voltage-dependent Na⁺ channel activation and other excitatory ligand-gated ion channels at pre- and post-synaptic sites. The overload of cytosolic Ca²⁺ levels caused by excitatory neurotransmitters or neurotoxins may initiate the persistent activation of Ca²⁺-dependent signaling, resulting in damage, for instance through apoptosis or necrosis. Although ginsenoside has no effects on ion channels and ligand-gated ion channels at rest state of neurons, ginsenoside might exhibit its effects by attenuation of cytosolic Ca²⁺ elevation by abnormal conditions by inhibiting ion channels and receptors (as indicated with “x” in arrow). The detailed explanations were described in text. Ginsenoside exhibits differential regulations on subsets of K⁺ channels. So, one possible hypothesis is that K⁺ channels regulated by ginsenoside might play a balancing role on Ca²⁺ and Na⁺ channel inhibitions by ginsenoside.