Network pharmacological analysis of ethanol extract of Morus alba linne in the treatment of type 2 diabetes mellitus

Abstract Diabetes is a chronic endocrine metabolism disorder that leads to hyperglycaemia. As the most common diabetic type, type 2 diabetes mellitus accounts for 90% of all diabetic disease with a key feature of insulin resistance. Mulberry leaves are commonly used in traditional Chinese medicine, and many studies confirm that mulberry leaves have positive effects on alleviating the pathological conditions of type 2 diabetes. However, its anti-diabetic effects and active ingredients are not completely understood. Compared with time- and cost-consuming experiments, network pharmacology provided a convenient method to systematically investigate the interactions between compounds in mulberry leaves and diabetes-related genes. Although similar network pharmacological studies were performed for mulberry leaves, only compounds sourced from public database or volatile components in the mulberry leaves were examined. In this study, we initially analysed the bioactive compounds from ethanol extract of mulberry leaves via liquid chromatography coupled with mass spectrometry, which generated a total of 248 components. A total of 14 active components and 49 potentially functional compounds were identified from TCMSP and PharmMapper database, respectively, which worked on 37 target proteins directly involved in the pathogenesis of T2DM. Kaempferol was shown to be the most influential active compound while androgen receptor was most widely regulated by compounds in the ethanol extract of mulberry leaves. Moreover, protein–protein interaction and target-pathway network analysis revealed that AKT1 was most important in the 37 target proteins in terms of its functions in different pathways and interactions with other target proteins. Moreover, pathway analysis showed that ethanol extract of mulberry leaves alleviated type 2 diabetes mellitus through pathways such as TNF signaling pathway, NF-κB signaling pathway, and insulin resistance pathway. In sum, this study provided a complete overview of the working mechanisms for the ethanol extract of mulberry leaves, the results of which could be used as a practical guidance for further experimental investigation of the functions of mulberry leaves during the treatment of type 2 diabetes mellitus.