Differential effect of bovine serum albumin on ginsenoside metabolite-induced inhibition of α3β4 nicotinic acetylcholine receptor expressed in Xenopus Oocytes

Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might play a role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside Rg₂-, CK-, or M4-induced regulation of α3β4 nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current (I_ACh) in oocytes expressing α3β4 nicotinic ACh receptor. Co-treatment of ginsenoside Rg ₂, CK, or M4 with ACh inhibited I_ACh in oocytes expressing α3β4 nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited I _ACh in oocytes expressing α3β4 nicotinic ACh receptor and co-treatment of ginsenoside Rg₂ or M4 but not CK with ACh inhibited I_ACh in oocytes expressing α3β4 nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of I _ACh in oocytes expressing α3β4 nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites.