Evaluation of Anti-Neuroinflammatory Activity of Isatin Derivatives in Activated Microglia

Abstract

Neuroinflammation plays a crucial role in the progression of Alzheimer’s disease and other neurodegenerative disorders. Overactivated microglia cause neurotoxicity and prolong the inflammatory response in many neuropathologies. In this study, we have synthesised a series of isatin derivatives to evaluate their anti-neuroinflammatory potential using lipopolysaccharide activated microglia as a cell model. We explored four different substitutions of the isatin moiety by testing their anti-neuroinflammatory activity on BV2 microglia cells. Based on the low cytotoxicity and the activity in reducing the release of nitric oxide, pro-inflammatory interleukin 6 and tumour necrosis factor α by microglial cells, the N1-alkylated compound 10 and the chlorinated 20 showed the best results at 25 µM. Taken together, the data suggest that 10 and 20 are promising lead compounds for developing new neuroprotective agents.

Sevoflurane Alters Serum Metabolites in Elders and Aging Mice and Increases Inflammation in Hippocampus

“…Of note, we noticed that a downregulated metabolite, isatin, which was substantially consistent with the secondary fragments of the standard substance ( Supplementary Figure 1 ), exhibited neuroprotective effects in different experimental models of neurodegeneration by enhancing cellular antioxidant, anti-inflammatory, and detoxification mechanisms. 25 , 26 …”

“…Of note, we noticed that a downregulated metabolite, isatin, which was substantially consistent with the secondary fragments of the standard substance (Supplementary Figure 1), exhibited neuroprotective effects in different experimental models of neurodegeneration by enhancing cellular antioxidant, anti-inflammatory, and detoxification mechanisms. 25,26 Thus, we explored whether isatin influences the biological function of microglial cells, considering that microglia are resident macrophages in the brain and sensitive to pathogens or damages by promoting the secretion of molecular signals to trigger reactive astrocytes. 27 To determine the potential cytotoxicity of isatin, we analyzed its dose-dependent effects on the survival of BV2 microglial cells.…”