Mechanism of effect of Zhuang medicine Semiliquidambar cathayen. Sis Chang on depression inflammation based on network pharmacology, molecular docking and animal experiments / 中国药理学通报

ABSTRACT

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen. sis Chang (JLBFH) by network pharmacology and molecular docking,etc, then to explore the mechanism of JLBFH' s effect on inflammatory response to depression through reserpine-induced depression rat model. Methods The target of drug and disease was predicted by network pharmacological database, protein interaction network diagram was constructed, biofunctional enrichment and pathways were analyzed, and molecular docking prediction was performed by AGFR software. Based on reserpine-induced depression, the role of JLBFH in depression inflammation was verified by behavior, molecular biology and pathological examination, and so on. Results A total of 13 active ingredients were screened, 11 key targets of JLBFH modulation of depression were selected, and the bioenrichment results were mainly related to cognition, prominent plasticity regulation, etc. The pathways were mainly related to Rapl signaling pathway, Toll-like receptor signaling pathways. The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice, markedly reduced the retention time in the circle of rats, increased serum levels of 5-HT and DA, decreased serum levels of IL-6, improved inflammatory infiltration in the prefrontal cortex, decreased brain tissue levels of IL-6,IL-1β ,TNF-α mRNA expression,and increased AKT1 mRNA expression in brain tissue. Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component, multi-target and multi-pathway, and the experimental validation results show that JLBFH can improve the d¬pression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.