A role for the carbohydrate portion of ginsenoside Rg₃ in Na⁺ channel inhibition

We showed recently that ginsenosides inhibit the activity of various types of ion channel. Here we have investigated the role of the carbohydrate component of ginsenoside Rg₃ in the inhibition of Na⁺ channels. The channels were expressed in Xenopus oocytes by injecting cRNAs encoding rat brain Nav1.2α and β1 subunits, and analyzed by the two-electrode voltage clamp technique. Treatment with Rg₃ reversibly inhibited the inward Na⁺ peak current (I_Na) with an IC₅₀ of 32.2 ± 4.5 μM, and the inhibition was voltage-dependent. To examine the role of the sugar moiety, we prepared a straight chain form of the second glucose and a conjugate of this glucose with 3-(4-hydroxyphenyl) propionic acid hydrazide (HPPH). Neither derivative inhibited I_Na. Treatment with the carbohydrate portion of ginsenoside Rg₃, sophorose [β-D-glucopyranosyl (1→2)-β-glucopyranoside], or the aglycone (protopanaxadiol), on their own or in combination had no effect on I _Na. These observations indicate that the carbohydrate portion of ginsenoside Rg₃ plays an important role in its effect on the Na ⁺ channel.