Abstract: Objective To explore the therapeutic mechanism of Liuwei Suanzao decoction (LWSZD) for perimenopausal insomnia (PI) based on network pharmacology. Methods TCMSP and Batman-TCM databases were searched for the active ingredients and targets of LWSZD and a herb- active ingredient-target network was constructed, and the disease targets were obtained from the OMIM, Genecards and Gene databases. The common targets were imported into STRING database and Cytoscape software to screen the core therapeutic targets, and GO enrichment and KEGG pathway analyses were performed using DAVID database. Molecular docking of the main active ingredients of LWSZD and the core targets was conducted using AutoDock, and the results were verified by observing the therapeutic effects of LWSZD and zolpidem in a rat model of PI induced by bilateral ovariectomy and intraperitoneal p-chlorophenylalanine injection. Results A total of 99 active ingredients, 389 drug targets, 187 PI-related targets, and 15 drug-PI common targets were screened. The core active ingredients were armepavine, sanjoinenine and mairin, and the core targets included ESR1, SIRT1, SERPINE1, COMT and CCL2, which were involved in the positive regulation of transcription from RNA polymerase II promoter, signal transduction, response to drug and positive regulation of transcription and in the pathways of dopaminergic synapses, tyrosine metabolism and tryptophan metabolism. Molecular docking results showed that LWSZD had a strong binding with ESR1, SIRT1 and SERPINE1 and was comparable to zolpidem. In the rat models of PI, treatment with LWSZD effectively alleviated the symptoms of insomnia (P<0.01), improved the levels of estrogen and other HPO axis-related hormones (P<0.05), and promoted the mRNA and protein expressions of ESR1 and SIRT1 in the hypothalamus tissues (P<0.01). Conclusion The active ingredients armepavine, sanjoinenine and mairin in LWSZD may synergistically regulate the expressions of ESR1, SIRT1 and SERPINE1 to improve PI in rats.

Key words: Liuwei Suanzao decoction, perimeno-pausal insomnia, network pharmacology, molecular docking, animal experiment