[Network analysis and experimental verification of Qingyan Formula in treatment of perimenopausal anxiety disorder]

This paper aims to explore the potential of Qingyan Formula(QYF) in the treatment of perimenopausal anxiety disorder(PAD) by network pharmacological method, and verify the pharmacodynamics and mechanism by using animal experiments. First, Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) was used to retrieve the active components of QYF. Then the potential drug targets were screened with use of Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine(TCMIP) v2.0 and Swiss Target Prediction database. Targets related to PAD were retrieved and screened from the OMIM database and GeneCards database. The intersection targets of QYF and PAD were screened out, and then the enrichment analysis of the signal pathways was conducted. Open field experiments and the O maze experiment were used to verify the pharmacodynamic effect of QYF in the treatment of PAD rats, and the serum neurotransmitter level was detected. The results showed that QYF may be have the function of regulating steroid hormone signaling pathways such as steroid hormone synthesis, ovarian steroidogenesis and estrogen signaling pathways, regulating central neurotransmitters signaling pathways including tryptophan metabolism pathways, Toll-like receptor signaling pathways, TGF-β signaling pathway and regulating inflammatory response pathways including NF-κB signaling pathway, Apelin signaling pathway, MAPK signaling pathway, TNF signaling pathway, and FOXO signaling pathway. All of the signaling pathways were related to PAD, which indicated that QYF may have the role of treating PAD. Qingyan Formula 70% ethanol extract(QYFE) revealed anxiolytic effects by extending the activity time and distance of anxious ovariectomized(OVX) rats in the central field of open field experiments, and increasing the duration and activity distance of anxious OVX rats in the open arm area in O maze experiments. QYFE increased serum serotonin/5-hydroxytryptamine(5-HT), and gamma aminobutyric acid(GABA) levels in anxious OVX rats, significantly reduced glutamate(Glu) and norepinephrine(NA) levels, and reversed the disturbance of excitatory/suppressive transmitter balance caused by OVX, which may be related to its effect on alleviating anxiety disorder in OVX rats.