Chen Huimin, Shen Jiajia, Li Haofeng, Zheng Xiao, Kang Dian, Xu Yangfan, Chen Chong, Guo Huimin, Xie Lin, Wang Guangji, Liang Yan
Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
J Ginseng Res. 2020 Jan;44(1):86-95. doi: 10.1016/j.jgr.2018.09.002. Epub 2018 Sep 19.
Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure.
The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora.
A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1.
The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of () increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with (1 × 10 CFU) by gavage 15 d before I/R surgery. Both Rb1 and upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and .
In sum, Rb1 exerts neuroprotective effects by regulating and GABA receptors rather than through direct distribution to the target sites.
人参皂苷Rb1（Rb1）是原人参二醇型人参皂苷中含量最丰富的一种，尽管其脑内暴露量较低，但仍具有出色的神经保护作用。
本研究旨在通过基于微生物群调节研究Rb1神经保护作用的机制，阐明Rb1药代动力学和药效学之间明显的矛盾。
建立了伪无菌（PGF）大鼠模型，比较了常规大鼠和PGF大鼠中Rb1的神经保护作用。对常见益生菌的相对丰度进行定量，以揭示在Rb1神经保护中占主导地位的真正益生菌。评估正常、缺血/再灌注（I/R）以及I/R+Rb1大鼠海马体和纹状体中γ-氨基丁酸（GABA）受体的表达，包括GABAA受体（α2、β2和γ2）和GABAB受体（1b和2），以揭示Rb1的神经保护机制。
结果表明，微生物群在Rb1的神经保护中起关键作用。用Rb1预处理后，（某种益生菌名称缺失）的相对丰度增加了15.26倍。在I/R手术前15天通过灌胃将（1×10CFU）（某种益生菌名称缺失）定殖于大鼠胃肠道，可预防I/R手术对梗死面积、神经功能缺损评分和促炎细胞因子（IL-1β、IL-6和TNF-α）的影响。Rb1和（某种益生菌名称缺失）均上调了I/R大鼠中GABA受体的表达。联合给予GABA受体拮抗剂可显著减弱Rb1和（某种益生菌名称缺失）的神经保护作用。
总之，Rb1通过调节（某种益生菌名称缺失）和GABA受体发挥神经保护作用，而不是通过直接分布到靶位点。
