Ginsenoside Rb1 exerts neuroprotective effects through regulation of abundance and GABA receptor expression.

BACKGROUND

Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure.

PURPOSE

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.

METHODS

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.

RESULTS

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 .

CONCLUSION

In sum, Rb1 exerts neuroprotective effects by regulating and GABA receptors rather than through direct distribution to the target sites.