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

The genus Scutellaria (Labiatae) is represented by 25 species in Turkish flora. Some of Scutellaria species are used as tonic, wound healing, hemostatic, antioxidant and antitumor in the world. This is a comparative study to evaluate cytotoxic efficacy of three endemic Scutellaria species; S. salviifolia Bentham (SS), S. glaphyrostachys Rech.f. (SG), S. rubicunda Hornem. subsp. brevibracteata J.R.Edm. (SB) against three different cell lines (HEp-2: human cervix epithelial carcinoma, HeLa: human cervix epithelial cancer cell lines and L929: mouse fibroblast non-cancerous cell line) by MTT method. For the activity tests, methanol extracts of the aerial parts were used. IC₅₀ values were found in a range of 378.0–494.7, 381.7–423.7 μg/ mL against HeLa and HEp-2 cell lines, respectively. All extracts showed lower cytotoxicity on L929 cell line than cancer cells with IC₅₀ value (753.0–1524.6 μg/mL). Due to the results, SB was the most effective extract to both cancer cell lines. SS and SG were more sensitive on HEp-2 than HeLa cell line. Our findings indicated that Scutellaria extracts have selective cytotoxic activity on both tested cancer and non-cancerous cell lines. This selectivity is important for discovery of new anticancer agents.