Background Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting a huge population worldwide. Teucrium polium L. has been used as a folk medicine for the treatment of T2DM in Anatolia, Turkey. The antihyperglycemic effect of the plant was reported previously. However, there was no detailed study on the underlying molecular mechanisms. In this study, we generated a research plan to clarify the active constituents of the extract and uncover the molecular mechanisms using network pharmacology analysis. Methods For this purpose, we composed a dataset of 126 compounds for the phytochemical profile of the aerial parts of T. polium. Drug-likeness of the compounds was evaluated, and 52 compounds were selected for further investigation. A total of 252 T2DM related targets hit by selected compounds were subjected to DAVID database. Results The KEGG pathway analysis showed enrichment for the TNF signaling pathway, insulin resistance, the HIF-1 signaling pathway, apoptosis, the PI3K-AKT signaling pathway, the FOXO signaling pathway, the insulin signaling pathway, and type 2 diabetes mellitus which are related to T2DM . AKT1, IL6, STAT3, TP53, INS, and VEGFA were found to be key targets in protein-protein interaction. Besides these key targets, with this study the role of GSK3β, GLUT4, and PDX1 were also discussed through literature and considered as important targets in the antidiabetic effect of T. polium. Various compounds of T. polium were shown to interact with the key targets activating PI3K-AKT and insulin signaling pathways. Conclusions According to these findings, mainly phenolic compounds were identified as the active components and IRS1/PI3K/AKT signaling and insulin resistance were identified as the main pathways regulated by T. polium. This study reveals the relationship of the compounds in T. polium with the targets of T2DM in human. Our findings suggested the use of T. polium as an effective herbal drug in the treatment of T2DM and provides new insights for further research on the antidiabetic effect of T. polium.

Scutellaria salviifolia Benth. (SS), an endemic plant for Turkey, is used for gastric ailments as folk medicine. In this study, we aimed to uncover the underlying molecular mechanisms with the help of network pharmacology and molecular docking analysis in the inflammation processes of gastric ailments. Gene enrichment analysis and target screening were carried out. Experimental validation was performed via cytokines of nitric oxide (NO) and interleukin-6 (IL-6) in LPS stimulated RAW 264.7 cells. Furthermore, antioxidant activity studies were performed by radical scavenging effects on different radicals. A total of 144 targets were listed for the isolated compounds where 26 of them were related to selected inflammation targets. According to the gene enrichment analysis, HIF1 signaling pathway and TNF signaling pathway were found to be involved in inflammation. We also defined AKT1, TNF, EGFR, and COX2 as key targets due to the protein-protein interactions of 26 common targets. The extract inhibited NO and IL-6 production at 100 and 200 µg/mL, while flavonoid-rich fraction possessed significant anti-inflammatory activity at the concentration of 50 and 100 µg/mL via NO and IL-6 production, respectively. It is thought that the anti-inflammatory effects of extracts, fractions and pure compounds were achieved by reducing NO and IL-6 levels via regulating the NF-κB pathway or reducing NO production by suppressing iNOS through the HIF-1 pathway when evaluated together with the results of network analysis and literature. Anti-inflammatory activities of the extract and fractions were promising and comparably with S. baicalensis, commonly used for its anti-inflammatory activity. Graphical Abstract Communicated by Ramaswamy H. Sarma