Influence of JuA in evoking communication changes between the small intestines and brain tissues of rats and the GABAA and GABAB receptor transcription levels of hippocampal neurons

Abstract

Ethnopharmacological relevanceJujuboside A (JuA) is a main active ingredient of semen ziziphi spinosae, which can significantly reduce spontaneous activity in mammals, increase the speed of falling asleep, prolong the sleeping time as well as improve the sleeping efficiency. In this study, the mechanism and the pathway of the sedative and hypnotic effect of JuA were investigated. Materials and methodsAfter being treated with JuA (in vitro), the rat׳s small intestine tissues cultures were used to stimulate the brain tissues. Then 27 cytokine levels were detected in the two kinds of tissue culture via liquid protein chip technology; In addition, the cultured hippocampal neurons of rat were treated with JuA, and γ-aminobutyric acid (GABA) receptor subunits (GABAAα1, GABAAα5, GABAAβ1 and GABABR1) mRNAs were evaluated by Real-time PCR. ResultsThe levels of IL-1α, MIP-1α, IL-1β and IL-2 were reduced significantly after 3h of treating the small intestine tissues with JuA (200µl/ml), and the concentration change rates, in order, were −59.3%, −3.59%, −50.1% and −49.4%; these cytokines were transmitted to brain tissues 2h later, which could lead to significant levels of reduction of IL-1α, IFN-γ, IP-10 and TNF-α; the concentration change rates were −62.4%, −25.7%, −55.2% and −38.5%, respectively. Further, the intercellular communication network diagram was mapped out, which could suggest the mechanism and the pathway of the sedative and hypnotic effect of JuA. The results also indicated that JuA (50µl/ml) increased significantly GABAAα1 receptor mRNAs and reduced GABABR1, mRNAs in hippocampal neurons after 24h of stimulation; however, all the mRNA transcription levels of GABAAα1,GABAAα5, GABAAβ1 and GABABR1 receptors increased significantly after 48h. ConclusionJuA performed its specific sedative and hypnotic effect through not only adjusting GABA receptors subunit mRNAs expression, but also down-regulating the secretion of relevant inflammation cytokines on the intestinal mucosal system to affect the intercellular cytokine network between nerve cells in the brain. This mechanism is similar to that of melatonin.