Plant extracts and omega-3 supplementation modulate hippocampal oxylipin profile in response to LPS-induced neuroinflammation

Neuroinflammation is a critical protective mechanism in healthy humans but can become harmful if chronic and/or unregulated, leading to neuronal damage and cognitive alterations. Microglia, which regulate inflammation in the brain, become dysfunctional with age, producing proinflammatory cytokines and contributing to chronic low-grade neuroinflammation. Oxylipins, which are lipid mediators synthesized from fatty acids, play dual roles in inflammation, promoting both initiation and resolution. Limiting inflammation and promoting resolution is a goal that could be achieved with nutrients such as polyphenols from grapes and blueberries, saffron carotenoids, and omega-3 fatty acids from fish, which have anti-inflammatory and proresolutive properties. Hence, this study explored the impact of an 18-day supplementation on neuroinflammation induced by lipopolysaccharide (LPS) in mice at different time points post-LPS treatment (30 min, 2 h, 6 h). Inflammatory, oxidative and neuroprotective gene expression; oxylipin quantification; and fatty acid composition were analyzed at each time point. Our results revealed that plant extracts (Memophenol™ and a patented saffron extract) and omega-3 supplementation induced changes in the resolution of inflammation through oxylipin production. In fact, the production of proinflammatory mediators in the hippocampus started earlier in the supplemented group than in the LPS group. Pro-resolving mediators derived from EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) were also found in higher quantities in supplemented mice. These changes were associated with increased hippocampal antioxidant status at 6 h post-LPS. These findings suggest that such dietary interventions with polyphenols, saffron carotenoids, and omega-3 fatty acids could be beneficial in preventing or mitigating age-related neuroinflammation and, consequently, age-related cognitive decline. Further research is needed to explore the effects of these supplements on chronic inflammation in the context of aging.