Lee Eunyoung, Kim Sunoh, Chung Kwang Chul, Choo Min-Kyung, Kim Dong-Hyun, Nam Ghilsoo, Rhim Hyewhon
Biomedical Research Center, Korea Institute of Science and Technology (KIST), 39-1 Hawholgok-dong Sungbuk-gu, Seoul 136-791, Republic of Korea.
Eur J Pharmacol. 2006 Apr 24;536(1-2):69-77. doi: 10.1016/j.ejphar.2006.02.038. Epub 2006 Feb 28.
Most herbal medicines that are orally administrated have been known to be metabolized before they are absorbed from the gastrointestinal tract. We, therefore, examined the effects of 20(S)-ginsenosides Rb1, Rg1 and Rg3, the three most commonly studied ginsenosides in the central nervous system, and their main metabolites on NMDA receptors using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques. Among the nine ginsenosides tested, 20(S)-ginsenoside Rh2 (20(S)-Rh2) along with 20(S)-ginsenoside Rg3 (20(S)-Rg3) produced the highest inhibitory effect in cultured hippocampal neurons. Although 20(S)-Rg3 and 20(S)-Rh2 selectively targeted NMDA receptors with similar potency, they produced additive effects and seemed to modulate different NMDA receptor regulatory sites. As a competitive antagonist, 20(S)-Rh2 seems to inhibit the receptor via its interaction with polyamine-binding sites, and 20(S)-Rg3 does so using glycine-binding sites. Therefore, these results suggest that the treatment of 20(S)-Rh2, a newly identified active ingredient of ginseng, might be a novel preventive candidate in treating neurodegenerative disorders.
大多数口服的草药在从胃肠道吸收之前就已被代谢。因此，我们使用基于fura-2的数字成像和穿孔全细胞膜片钳技术，研究了20(S)-人参皂苷Rb1、Rg1和Rg3（中枢神经系统中研究最多的三种人参皂苷）及其主要代谢产物对NMDA受体的影响。在所测试的九种人参皂苷中，20(S)-人参皂苷Rh2（20(S)-Rh2）与20(S)-人参皂苷Rg3（20(S)-Rg3）对培养的海马神经元产生了最高的抑制作用。尽管20(S)-Rg3和20(S)-Rh2以相似的效力选择性地作用于NMDA受体，但它们产生了相加效应，并且似乎调节不同的NMDA受体调节位点。作为竞争性拮抗剂，20(S)-Rh2似乎通过与多胺结合位点相互作用来抑制受体，而20(S)-Rg3则通过甘氨酸结合位点来抑制受体。因此，这些结果表明，人参新鉴定的活性成分20(S)-Rh2的治疗可能是治疗神经退行性疾病的一种新型预防候选药物。
