Interactions between phenolic constituents of Scutellaria salviifolia and key targets associated with inflammation: network pharmacology, molecular docking analysis and in vitro assays

• Published in: Journal of biomolecular structure & dynamics Vol. 41; no. 4; pp. 1281 - 1294
• Main Authors: Dogan, Zeynep, Kutluay, Vahap Murat, Genc, Yasin, Saracoglu, Iclal
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.03.2023
• Subjects: anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Humans; Inflammation - drug therapy; Interleukin-6; Lamiaceae; Lipopolysaccharides; Molecular Docking Simulation; Network Pharmacology; NF-kappa B - metabolism; Nitric Oxide; Plant Extracts - pharmacology; Scutellaria - metabolism; Scutellaria salviifolia; target prediction; target prediction; Lamiaceae; Scutellaria salviifolia; network pharmacology; anti-inflammatory activity
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.2019119

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. Communicated by Ramaswamy H. Sarma