Abstract
Background: Chaihu-Shugan-San (CSS) is a traditional Chinese medicine (TCM) mainly treated liver constraint and spleen deficiency about 2200 years' history that analogous to depression comorbidity with functional dyspepsia. ZhikeShaoyao(ZS) drug pair plays a pivotal role in CSS. From this clue, we try to find a new antidepressant with polypharmacological mechanisms. In vivo antidepressive and prokinetic comparisons between ZS and its absorbed compound, synephrine, were made. Methods: These antidepressant effects were studied using behavioral tests including forced swimming test (FST), tail suspension test (TST) and open field test (OFT) in the chronic unpredictable mild stress (CUMS) rat model. In order to compare the anti-inflammatory effects, we use ELISA kits and Quantitative real-time PCR to detect IL-1β, IL-6 and TNF-α in the hippocampus. Using LPS to establish BV2 cell inflammation model observes the effect of ZS and synephrine. Moreover, Liquid chromatography-mass spectrometry (LC-MS) is used to determine bioactive absorption of synephrine in the hippocampus and gut of CUMS rat. Results: ZS and synephrine significantly reduce the immobility time of FST, TST, OFT experiment (P<0.05),effectively improve the levels of 5-hydroxytryptamine (P<0.05, P<0.05), noradrenaline (P<0.001, P<0.001), and inhibit the expressions of proinflammatory cytokines in BV2 cell inflammation model and CUMS model, Moreover, they enhance the level of gastrointestinal motility hormones acyl ghrelin (P<0.01, P<0.05), ghrelin (P<0.05, P<0.001), in the gastric antrum tissue and plasma, and effectively facilitate gastrointestinal motility. For the LC-MS analysis, the synephrine was discovered in the hippocampus. Conclusion: In summary, our findings demonstrate that ZS and synephrine may be effective natural antidepressants by enhancing monoamine neurotransmitters, inhibiting inflammation, and elucidating the potential mechanism of A&P, which might blaze potential way of opening up new therapeutic avenues for depression.
This work was supported by National Natural Science Foundation of China (No.30070932, 30271648, 30325045, 30572339, 81072967, 81173591, 81373855 and 81573797). A project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (integration of Chinese and western medicine) and high-level talents of Nanjing University of Chinese Medicine.
