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

Ethnopharmacological relevance: Jujuboside 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 methods: After 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 gamma-aminobutyric acid (GABA) receptor subunits (GABA(A)alpha(1), GABA(A)alpha(5), GABA(A)beta(1) and GABA(B)R(1)) mRNAs were evaluated by Real-time PCR. Results: The levels of IL-1 alpha, MIP-1 alpha, IL-1 beta and IL-2 were reduced significantly after 3 h of treating the small intestine tissues with JuA (200 mu l/ml), and the concentration change rates, in order, were -593%, -3.59%, -50.1% and -49.4%; these cytokines were transmitted to brain tissues 2 h later, which could lead to significant levels of reduction of IL-1 alpha, IFN-gamma, IP-10 and TNF-alpha; the concentration change rates were -62.4%, -25.7%, -552% 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 (50 mu l/ml) increased significantly GABA(A)alpha(1), receptor mRNAs and reduced GABA(B)R(1), mRNAs in hippocampal neurons after 24 h of stimulation; however, all the mRNA transcription levels of GABA(A)alpha(1),GABA(A)alpha(5), GABA(A)beta(1) and GABA(B)R(1) receptors increased significantly after 48 h. Conclusion: JuA 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.