Lipophilic Bioactive Compounds Transported in Triglyceride-Rich Lipoproteins Modulate Microglial Inflammatory Response

Microglial cells can contribute to Alzheimer's disease by triggering an inflammatory response that leads to neuronal death. In addition, the presence of amyloid-beta in the brain is consistent with alterations in the blood-brain barrier integrity and triglyceride-rich lipoproteins (TRL) permeation. In the present work, we used lab-made TRL as carriers of lipophilic bioactive compounds that are commonly present in dietary oils, namely oleanolic acid (OA), alpha-tocopherol (AT) and beta-sitosterol (BS), to assess their ability to modulate the inflammatory response of microglial BV-2 cells. We show that treatment with lab-made TRL increases the release and gene-expression of IL-1 beta, IL-6, and TNF-alpha, as well as NO and iNOS in microglia. On the other hand, TRL revealed bioactive compounds alpha-tocopherol and beta-sitosterol as suitable carriers for oleanolic acid. The inclusion of these biomolecules in TRL reduced the release of proinflammatory cytokines. The inclusion of these biomolecules in TRL reduced the release of proinflammatory cytokines. AT reduced IL-6 release by 72%, OA reduced TNF-alpha release by approximately 50%, and all three biomolecules together (M) reduced IL-1 beta release by 35% and TNF-alpha release by more than 70%. In addition, NO generation was reduced, with the inclusion of OA by 45%, BS by 80% and the presence of M by 88%. Finally, a recovery of the basal glutathione content was observed with the inclusion of OA and M in the TRL. Our results open the way to exploiting the neuro-pharmacological potential of these lipophilic bioactive compounds through their delivery to the brain as part of TRL.