Antidepression and Prokinetic Effects of Paeoniflorin on Rats in the Forced Swimming Test via Polypharmacology

Paeoniflorin, an organic compound extracted from the roots of the white peony (Paeonia lactiflora) plant, has previously been shown to exert antidepression and prokinetic effects. The traditional Chinese prescription Si-Ni-San, of which paeoniflorin is a constituent, is often used in treating depression and functional gastrointestinal disorders. The effectiveness of Si-Ni-San has been shown to be less effective in a paeoniflorin-deleted form. The present study further investigates whether paeoniflorin alone is as effective as herbal prescriptions in which the compound is a constituent, specifically any antidepressive and prokinetic effect on rats subjected to a forced swimming test (FST). The FST was used to establish the depression model. Sprague-Dawley rats were administrated with 10 mg/kg paeoniflorin by gastrogavage three times before the behavioral test and gastrointestinal motility tests, respectively. In antidepression studies, fluoxetine was used as the positive control. In order to determine the effect of paeoniflorin on the gastrointestinal movement, mosapride was used as the positive control. Plasma and hippocampus monoamine, hypothalamic-pituitary-adrenal axis, plasma brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), ghrelin, motilin, and hippocampus nitric oxide (NO) were assessed using an enzyme-linked immunosorbent assay (ELISA). Gastrointestinal (GI) motility was measured in vivo and in vitro. Rats subjected to FST showed decreased gastric emptying and intestinal transit in vivo, decreased plasma and hippocampus 5-hydroxytryptamine, norepinephrine, dopamine, ghrelin, motilin, and reduced plasma BDNF and SOD as well as increased plasma and hippocampus corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone, plasma MDA, and hippocampus NO. Paeoniflorin reversed these symptoms in a similar manner to fluoxetine and mosapride, respectively. In vitro, paeoniflorin can stimulate the jejunal contract of healthy rats dose-dependently. The results suggest that paeoniflorin can simultaneously exert antidepression and prokinetic effects via polypharmacology.