Elucidation of the molecular mechanism of Sanguisorba Officinalis L. against leukopenia based on network pharmacology

Abstract

Leukopenia is the most common hallmark of hematopoietic diseases in clinic. Sanguisorba Officinalis L., a traditional Chinese medicine, has long been used for alleviating leukopenia. However, its associated mechanism still remains unknown. In this study, a network pharmacology approach was used to elucidate the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia. Firstly, 12 active compounds of Sanguisorba Officinalis L. were identified through TCMSP database with absorption, distribution, metabolism, excretion (ADME) screening, and UHPLC-MS analysis. Then, 258 leukopenia related targets of the identified active compounds were predicted via the Swiss Target Prediction database, GeneCards database and DisGeNET database, respectively. After taking the intersection of two related targets, 72 common targets were selected. Among them, 8 core targets (VEGFA, HSP90AA1, EGFR, PTGS2, MTOR, ESR1, ERBB2, MDM2) of Sanguisorba Officinalis L. against leukopenia were obtained through the topological analysis. Meanwhile, both the GO and KEGG pathway analysis reveal that the core targets are mainly enriched in PI3K-Akt, HIF-1, VEGF and estrogen signaling pathways. In addition, molecular docking simulation was performed to explore the binding ability between the 12 active compounds of Sanguisorba Officinalis L. with 8 core targets. Furthermore, a myelosuppressive mice model was established to evaluate the protective effect of Sanguisorba Officinalis L. against leukopenia. The results showed that the ethanol extract of Sanguisorba Officinalis L. significantly raised the number of peripheral white blood cells. Overall, this study provides an insight into the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia, which lays a theoretical foundation for the further experimental verification and clinical application.

Keywords: Leukopenia; Molecular mechanism; Network pharmacology; Sanguisorba Officinalis L.; White blood cells.