Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Korean J Physiol Pharmacol. 2013 Apr;17(2):127-32. doi: 10.4196/kjpp.2013.17.2.127. Epub 2013 Apr 10.
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 γ-aminobutyric acid receptorC (GABAC) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on GABAC receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant GABAC receptor (ρ1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing GABAC 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 (IGABA ). Interestingly, pre-application of M4 inhibited IGABA 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 µM, respectively. Inhibition of IGABA by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate GABAC receptor channel activity in the brain, including in the eyes.
人参中的一种活性成分——人参皂苷，显示出多种药理和生理作用，它们被肠道微生物转化为化合物 K（CK）或原人参三醇（M4）。CK 是原人参二醇（PD）人参皂苷的代谢物，而 M4 是原人参三醇（PT）人参皂苷的代谢物。γ-氨基丁酸受体 C（GABAC）主要在视网膜双极细胞和大脑的几个区域表达。然而，对于人参皂苷代谢物对 GABAC 受体通道活性的影响知之甚少。在本研究中，我们使用双电极电压钳技术研究了 CK 和 M4 对在非洲爪蟾卵母细胞中表达的人重组 GABAC 受体（ρ1）通道活性的影响。在表达 GABAC 受体 cRNA 的卵母细胞中，我们发现 CK 或 M4 单独使用对卵母细胞没有影响。然而，CK 或 M4 与 GABA 共同应用抑制 GABA 诱导的内向峰值电流（IGABA）。有趣的是，M4 以剂量依赖性和可逆转的方式比 CK 更有效地抑制 IGABA。CK 和 M4 的半抑制浓度（IC50）值分别为 52.1±2.3 和 45.7±3.9 µM。IGABA 的抑制作用与电压无关且非竞争性。这项研究表明，人参皂苷代谢物可能调节大脑中的 GABAC 受体通道活性，包括在眼睛中。
