Inhibitory Effects of Ginsenoside Metabolites, Compound K and Protopanaxatriol, on GABA<SUB>C</SUB> Receptor-Mediated Ion Currents

Inhibitory Effects of Ginsenoside Metabolites, Compound K and Protopanaxatriol, on GABA<SUB>C</SUB> Receptor-Mediated Ion Currents

Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The &#1347;-aminobutyric acid receptor_C (GABA_C) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on GABA_C receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant GABA_C receptor (&#1361;1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing GABA_C receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current (I_GABA). Interestingly, pre-application of M4 inhibited I_GABA more potently than CK in a dose- dependent and reversible manner. The half-inhibitory concentration (IC₅₀) values of CK and M4 were 52.1±2.3 and 45.7±3.9 &#1356;M, respectively. Inhibition of I_GABA by CK and M4 was voltage-independent and non- competitive. This study implies that ginsenoside metabolites may regulate GABA_C receptor channel activity in the brain, including in the eyes.