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Objective. To evaluate the potential drug-drug interactions of the Shuganjieyu capsule by establishing a Chronic Unpredictable Mild Stress (CUMS) depression model combined with the Cocktail probe substrate method. Methods. The whole study was divided into the single-dose and multiple-dose groups. Animals were randomly divided into further subgroups in each group. Following chronic unpredictable mild stress model development, Shuganjieyu capsules were administered to the drug administration group. The single-dose subgroup received the drug for one day, and the multiple-dose subgroup received the drug for three months. Liver microsomes of each group were extracted, and the effects of the Shuganjieyu capsule on the CYP450 enzyme were investigated by liquid chromatography-mass spectrometry (LC-MS) (LC-MS) based on the Cocktail probe substrate method. The immunohistochemical method and RT-qPCR were used to detect the activity of CYP450 immunoprotein in rat liver. Results. In the single-dose subgroup, there were no statistical differences between the administration and model groups. In the multiple-dose subgroup, the conversion and protein expression rates of CYP1A2 and CYP2C19 were significantly increased in the model group compared with the blank group. In the administration group, the conversion and protein expression rates of CYP1A2 and CYP2C19 were inhibited. Conclusion. Long-term administration of the Shuganjieyu capsule could relieve depression-related behaviors in CUMS rats and downregulate the CYP1A2 and CYP2C19 enzyme activities in CUMS rats by inhibiting the expression of CYP1A2 and CYP2C19 protein. Long-term administration of the Shuganjieyu capsule may affect the bioavailability of other drugs metabolized by CYP1A2 and CYP2C19 enzymes, but the clinical guidance’s specific significance needs to be clarified further.

Background: Inflammation is a common pathological phenomenon when homeostasis is seriously disturbed. Phillygenin (PHI) is a lignin component isolated from Forsythiae Fructus, which showed a good anti-inflammation effect. However, the mechanisms of PHI on anti-inflammation have not yet been systematically elucidated.Methods: In the study, the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to investigate mechanisms of PHI on inflammation. The effect of PHI on LPS-induced IL-1β and PGE2 inflammatory factors was detected by ELISA, and the mRNA expression of IL-1β, IL-6 and TNF-α was detected by RT-qPCR. Proteomics studies the signaling pathways that may be affected by PHI. Molecular docking technology was used to study the possible targets of PHI on NF-kB pathway. Western blot was performed to detect progressive changes in protein expression.Results: The research showed that PHI significantly inhibited the robust increase of IL-1β and PGE2, and lowered the transcriptional level of inflammatory genes including IL-6, IL-1β and PGE2 in LPS-stimulated RAW264.7 cells. Proteomics results indicated that PHI was involved in the regulation of multiple signaling pathways. Molecular docking results indicated that PHI has an affinity for most proteins in NF-kB pathway. Western blot analysis showed that PHI inhibited LPS-induced NF-κB pathway activation. Conclusion: PHI inhibits the activation of NF-κB pathway, thereby inhibiting the expression of related inflammatory genes and the release of cytokines, thus showing remarkable anti-inflammatory effect.