AUTHOR=Zong Yang , Chen Ting , Dong Hongli , Zhu Lijing , Ju Wenzheng 

TITLE=Si-Ni-San Prevents Reserpine-Induced Depression by Inhibiting Inflammation and Regulating CYP450 Enzymatic Activity

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 10 - 2019

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01518

DOI=10.3389/fphar.2019.01518

ISSN=1663-9812

ABSTRACT=Depression is becoming a major global health issue. Si-Ni-San is a famous formula in Traditional Chinese Medicine with the powerful anti-depressant. However, the mechanism of the antidepressant action of Si-Ni-San has not been clearly elucidated. In this study, the establishment of reserpine-induced depression rats were evaluated by using behavioral tests. The quantitative analysis of Si-Ni-San by HPLC-DAD. The serum, hepatic and hippocampus levels of IL-1β, IL-6 and TNF-α were measured by ELISA, respectively. Furthermore, the key proteins for NF-κB, BDNF and its receptor TrkB were analyzed by WB in liver and hippocampus, respectively. CYP450 enzymes activity were performed using LC-MS/MS in conjunction with drug and statistics (DAS 3.0) after oral administration of six probe-drugs. Behavioral tests including Forced swim test, Sugar water preference test and Open field test were performed to certificate the model was successfully established. ELISA experiments showed that Si-Ni-San attenuated reserpine-induced increases in IL-1β, IL-6 and TNF-α expression in the serum, hepatic and hippocampus. In addition, WB experiments showed that Si-Ni-San can increase the levels of NF-κB, BDNF and its receptor TrkB in the hippocampus of rats. According to the pharmacokinetic parameters, Si-Ni-San had moderate inhibitory effects on reserpine induced depression models, CYP1A2, 2D1, 2E1, 3A2, but no significant metabolic changes on CYP2C6 and 2D2. The results show that Si-Ni-San has a better protective effect on the depressive symptoms induced by reserpine, which may be related to the improvement of the inflammatory factor, the level of the brain-derived neurotrophic factor and the activity of CYP450 enzymes.