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To investigate the effects and potential mechanisms of action of Panax notoginseng (Burk) F. H. Chen (P. notoginseng, San Qi) flowers in type 2 diabetes mellitus (T2DM) using network pharmacology, in vivo experiments, and RNA sequencing (RNA-seq).
Network pharmacology analysis was performed to identify and correlate the drug targets of flower buds of P. notoginseng (PNF) with T2DM disease targets and to predict the key targets and pathways involved in the therapeutic effects of PNF in T2DM. In vivo experiments were conducted to assess the effects of PNF on glucose and lipid metabolism in mice with T2DM. RNA-seq was performed, and the results were integrated with network pharmacology data to assess the therapeutic mechanisms of PNF in T2DM. The results from transcriptomics and network pharmacology were validated using real-time polymerase chain reaction.
A total of 27 intersecting targets were identified by overlapping 35 drug targets with T2DM targets. Further topological analysis using the Centiscape 2.2 tool revealed five core targets, including signal transducer and activator of transcription 3 (STAT3). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the JAK/STAT signaling pathway is a key mechanism underlying the therapeutic effects of PNF in T2DM. In vivo experiments confirmed that PNF effectively regulates glycolipid metabolism in a mouse model of diabetes. KEGG pathway enrichment analysis of RNA-seq data highlighted the JAK2/STAT3 and PI3K/AKT pathway as a potential mechanism. PNF high-dose (PNFH) increased the gene expression levels of PIK3R1 and AKT2, decreased the expression of PCK1, JAK2, and STAT3, and showed a trend toward increasing INSR expression without reaching statistical significance.
PNF improves glycolipid metabolism disorders in T2DM, potentially by modulating the JAK2/STAT3 and PI3K/AKT signaling pathway.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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