Data Availability StatementThe datasets generated for this research can be found on demand towards the corresponding writer. test were evaluated to ensure the establishment of depressive rats. The levels of IL-1, IL-6, and TNF- in the serum, liver, and hippocampus of rats were measured by enzyme-linked immunosorbent assays (ELISA). Furthermore, the key proteins NF-B, BDNF, and TrkB were analyzed by Western blot (WB) analysis in the hippocampus. In addition, CYP450 enzymatic activity analysis was performed using LC-MS/MS in conjunction with drug and statistics (DAS 3.0) after dental administration of six probe medicines. Our results showed that SNS attenuated reserpine-induced raises in IL-1, IL-6, and TNF- manifestation in the serum, liver, and hippocampus. The levels of NF-B, BDNF, and TrkB in the hippocampus of depressive rats were also modified. According to the pharmacokinetic guidelines, SNS experienced moderate inhibitory effects in the reserpine-induced major depression model on CYP1A2, CYP2D1, CYP2E1, and CYP3A2, but no significant metabolic changes to CYP2C6 and CYP2D2. These findings suggested that SNS has a protective effect on reserpine-induced depressive rats, which may be related to the improvement of the inflammatory factors, the level of BDNF and the activity of CYP450 enzymes. (Chaihu), (Shaoyao), (Zhishi), and (Gancao) (Hu et al., 2016). Generally, adult individuals take orally 100 ml of SNS in the dose of 0. 09 g/ml twice per day time according to the suggestion Phloridzin distributor of traditional Chinese physician. SNS can soothe the liver, remove internal warmth, strengthen the spleen, and nourish the blood. Furthermore, it has been clinically applied for the improvement of mental diseases, including depression and other conditions (Shen et al., 2016). Although SNS has certain clinical effects in the treatment of depression (Wang et al., 2009), the lack of rigorous experimental research counteracts the unique advantages of TCM, which seriously hinders its promotion and application worldwide. Recently, clinical and preclinical evidence have suggested that inflammation is associated with the complicated pathophysiology of depression (Kaufmann et al., 2017; Pfau et al., 2018; Chan et al., 2019). Patients with depression exhibited an upregulation of proinflammatory cytokines, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor- (TNF-) (Kennedy et al., 2009). NF-B has been known to act as an essential transcription factor for the expression of inflammatory mediators, such as iNOS, COX-2, IL-1, and TNF-, which leads to depressive-like behavior (Lawrence and Fong, 2010; Biesmans et al., 2013; Yuan et al., 2015). Phloridzin distributor BDNF and its receptor TrkB are distributed in the central nervous system widely, in the cerebral cortex and hippocampus specifically, having a significant influence for the success, development, Phloridzin distributor and differentiation of neurons. Currently, it really is generally thought that a reduction in BDNF and TrkB proteins levels relates to the event of melancholy, and antidepressant treatment can enhance the degrees of BDNF and TrkB (Duman and Monteggia, 2006). Consequently, this scholarly study evaluated the efficacy of SNS by discovering these biomarker changes in depressive rats. The multi-target and multi-component characteristics of TCM determine the complexity of its mechanism of action. The evaluation Mst1 from the enzymatic actions of the primary active ingredients can offer a medical basis for understanding the logical application and system of TCM (Li et al., 2013). Generally, the clinical need for metabolic interactions because of enzyme inhibition is a lot higher than that of enzyme advertising, accounting for about 70% of most relationships in the enzyme program. The inhibition of CYP450 enzymes from the active component in TCM can decrease the eradication of rate of metabolism of additional TCM elements or chemical medicines, break the total amount between the mixed medicines and their metabolites, boost their bloodstream trigger or focus build up, and may result in an improvement in the medication efficacy. However, effects or poisonous reactions occur. Consequently, evaluating the result of the substances of Phloridzin distributor TCM on CYP450 enzymatic activity can be of great significance for both clinical protection and reducing the chance of drug-drug relationships (Overholser and Foster, 2011). Cocktail evaluation using probe medicines can be used to efficiently study the activity of various CYP enzymes (Lammers et al., 2016). In this study, we described the development and validation of six probe drugs for CYP1A2, CYP2C6, CYP2D1, CYP2D2, CYP2E1, and CYP3A2 using LC-MS/MS to determine CYP450 enzymatic activities in rats. The probe drugs cocktail comprised six representative substrates: theophylline (THE) for CYP1A2, tolbutamide (TOL) for CYP2C6, omeprazole (OME) for CYP2D1, dextromethorphan (DXT) for CYP2D2, chlorzoxazone (CZX) for CYP2E1, and midazolam (MDZ) for CYP3A2. Therefore, in order to evaluate the curative effect of SNS, biochemical indexes such as proinflammatory cytokines in the hippocampus, serum, and liver tissue were measured in reserpine-induced depressive rats. To elucidate the effect of SNS on CYP450 enzymatic.