An Integrative Approach to Investigate the Mode of Action of (-)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology.

Abstract

Bacterial meningitis remains one of the most prevalent infectious diseases worldwide. Although advances in medical care have improved mortality and morbidity, neurological complications remain high. Therefore, aside from antibiotics, therapeutic adjuvants targeting neuroinflammation are essential to combat the long-term neuronal sequelae of bacterial meningitis. In the present study, we propose (-)-dendroparishiol as a potential add-on therapy to improve neuroinflammation associated with bacterial meningitis. The biological activity of (-)-dendroparishiol was first predicted by computational analysis and further confirmed in vitro using a cell-based assay with LPS-induced BV-2 microglial cells. Biological pathways involved with (-)-dendroparishiol were identified by applying network pharmacology. Computational predictions of biological activity indicated possible attenuation of several inflammatory processes by (-)-dendroparishiol. In LPS-induced BV-2 microglial cells, (-)-dendroparishiol significantly reduced the expression of inflammatory mediators: iNOS, NO, COX-2, IL-6, and TNF-α. Molecular docking results demonstrated the potential iNOS and COX-2 inhibitory activity of (-)-dendroparishiol. Network pharmacological analysis indicated the plausible role of (-)-dendroparishiol in biological processes involved in oxidative stress and neuroinflammation with enrichment in neuroinflammatory pathways. Overall, this study provides scientific evidence for the potential application of (-)-dendroparishiol in the management of bacterial meningitis-associated neuroinflammation.