Prokinetic meranzin hydrate from Chaihu-Shugan-San improves depression-like behaviors and hypomotility in rats via ghrelin and neurocircuitry

Abstract

Background Depression and functional dyspepsia (FD) are characterized by comorbidity, overlapping depression, and nausea. The pathogenesis of depression and FD is mediated by α2-adrenoreceptor and/or ghrelin. Antidepressant (A) or prokinetic (P) agents are numerous, but few have been investigated in this context. Ancient Gan-zhu-shu-xie (GZSX), whose representative traditional Chinese medicine(TCM) is Chaihu-Shugan-San (CSS), may exert antidepressant effects with prokinetic meranzin hydr-ate (MH) via α2-adrenoreceptors in the acute forced swimming (FS) test in rats.Therefore, the main aim of the study is to investigate the acute antidepressant and prokinet-ic effects of CSS and MH after acutely FS on rats, and its possible mechanism. Methods FS rats were treated with CSS, MH, fluoxetine, ghrelin antagonist [D-Lys3]-GHRP-6, and take a series of behavior tests and gastrointestina motility tests, and via 7.0 T fMRI-BOLD signal, compared with well-known mechanism of positive control. Results MH has similar effects to CSS-stimulated deactivation when comparedto those of fluoxetine (4.02-fold for hippocampus and 1.45-fold for thalamus). The ghrelin antagonist [D-Lys3]-GHRP-6 synchronously inhibited A&P and BOLD HTB foci. Prokinetic mosapride had effects on the thalamus and basal ganglia but not the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. Conclusion These data show that on acute FS-stimulated DB&H, MH-induced rapid A&P, and ghrelin-related regulation coupled to BOLD signals in brain areas before, providing insight into a unified theory of depression pathogenesis and pharmacotherapy.