Antidepressant-like effect of 5-O-methylvisammioside targeting SRC is accompanied by hippocampal neuroinflammation reduction in lipopolysaccharide-challenged mice

Abstract

Abstract 5-O-methylvisammioside (MeV), a phenolic compound found in the underground part (radix) Saposhnikovia divaricate (Turcz. ex Ledeb.) Schischk. (Apiaceae) in the early stage, has also been detected in the extract of Eranthis longistipitata(Ranunculaceae) in recent literature. In previous studies, it was discovered to have anti-inflammatory and neuroprotective activities. However, the potential mechanisms of MeV antidepressants remain unclear. In the present study, Network pharmacology was adopted to conduct drug-target networks following obtaining the shared targets between MeV and major depressive disorder (MDD) in multiple databases. The binding ability of the compound to the core target was verified through molecular docking. In addition, the biological processes and signaling pathways involved in the antidepressant effect of MeV by animal experiments. Our results were as follows: i) There were 85 shared targets of MeV & MDD in multiple public databases. The target protein with a higher degree in the protein-protein interaction (PPI) network was Proto-oncogene tyrosine-protein kinase Src (SRC). ii) Gene Ontology analysis showed that MeV treatment of MDD mainly involves the positive regulation of phosphorylation, the response to lipopolysaccharide, and other biological processes. It was closely related to the nuclear factor kappa B (NF-κB) signaling pathway. iii) MeV administration significantly alleviated depression-like behaviors and reduced microgliosis in mice by inhibiting SRC phosphorylation. The antidepressant effects of MeV may be attributed to the NF-κB signaling pathway. The results may contribute to demonstrating the effectiveness of MeV against MDD and facilitate the development of new traditional Chinese medicine ingredients.