[Investigation of antidepressant active components and mechanisms of total triterpenoids of Wolfiporia cocos based on serum pharmacochemistry combined with network pharmacology and experimental validation].

Based on the total triterpenoids of Wolfiporia cocos(TTWC) in the serum of depressed rats, this study combined network pharmacology, molecular docking, and experimental validation to explore the antidepressant active components and mechanisms of TTWC. Firstly, ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was used to identify the blood-entering components of TTWC. Then, network pharmacology and molecular docking were used to predict the potential antidepressant active components and mechanisms of TTWC. Finally, an in vitro model constructed using lipopolysaccharide(LPS)-treated BV2 cells was used to validate the main active components. A total of 38 triterpenoid components of W. cocos were detected in the blood. Thirty potential active components were obtained through screening by network pharmacology, and 122 component-disease overlapping targets were obtained, which showed that interleukin(IL)-6, tumor necrosis factor(TNF), Albumin(ALB), non-receptor tyrosine kinase(SRC), and IL-1β might be the core targets. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment results indicated that the antidepressant effect of TTWC might be influenced by neuroactive ligand-receptor interaction signaling pathway, Fc ε RI signaling pathway, TNF signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. The molecular docking results showed that the potential antidepressant active components of TTWC had a good binding effect with the core targets. The results of cell assays showed that TTWC and nine components, including pachymic acid and pachymic acid A, reduced the secretion levels of tumor necrosis factor-α(TNF-α), IL-6, IL-1β, IL-18, and nitric oxide(NO) to varying degrees and down-regulated the protein expression levels of phosphorylated p38 mitogen-activated protein kinase(p-p38) and phosphorylated c-Jun amino-terminal protein kinase(p-JNK). Comparison of the results of the experiments in each group showed that there were differences in the potency and main targets of the components. On the basis of previous studies, the present study explored the antidepressant active components of TTWC and demonstrated that they can effectively reduce the secretion of inflammatory factors and inflammatory mediators, and realize the control of neuroinflammation through the regulation of the MAPK pathway. The results of this study showed that TTWC inhibited neuroinflammation in a multi-component, multi-target, and multi-pathway manner, thus realizing the antidepressant effect.