Investigation on the Mechanism of Antidepressant Effect of Cinnamomi Cortex Based on Network Pharmacology and Experimental Verification

OBJECTIVE To explore the mechanism of Cinnamomi Cortex in the treatment of depression based on the network pharmacology method, and to verify the experimental results according to the results. METHODS The potential active components of Cinnamomi Cortex were screened by using the Chinese Medicine System Pharmacology Database Analysis Platform(TCMSP) and literatures related to the active components of Cinnamomi Cortex. The target of action of the active ingredients obtained by screening was predicted; the disease targets of depression were obtained from the DisGeNet database; the STRING database protein-protein interaction was used to construct PPI network; Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis for key targets through DAVID database. Based on the results of network pharmacology, the solid self-microemulsion of Cinnamomi Cortex oil was used as a reagent to establish a chronic unpredictable mild stress(CUMS) depression mice model, and the experimental verification was carried out by measuring the expression levels of neurotransmitters and inflammatory factors in mice. RESULTS A total of 22 active ingredients and 186 potential targets were obtained through screening. A total of 275 GO items were obtained by GO enrichment analysis, including 222 for biological processes, 18 for cellular composition, and 35 for molecular functions. A total of 96 signaling pathways were obtained from KEGG enrichment. The results of network pharmacology indicated that the antidepressant mechanism of Cinnamomi Cortex was related to neurotransmitter components and inflammatory response. The results of animal experiments indicated that Cinnamomi Cortex oil solid self-microemulsion could improve hippocampal damage caused by CUMS, and make neurons in the hippocampus neatly arranged and cell structure intact. At the same time, it could effectively increase the expression levels of 5-hydroxytryptamine(5-HT), NE and DA in the brain of CUMS mice(P<0.05), and reduce the expression levels of serum IL-6, IL-1β and TNF-α(P<0.05). The results of animal experiments were consistent with the results of network pharmacology. CONCLUSION The antidepressant activity of Cinnamomi Cortex has the characteristics of multi-component, multi-target and multi-pathway. Regulating the expression levels of neurotransmitters and inflammatory factors is an important way of its action, which provides a basis for the in-depth study of the antidepressant mechanism of Cinnamomi Cortex.