A Nonpolar Blueberry Fraction Blunts NADPH Oxidase Activation in Neuronal Cells Exposed to Tumor Necrosis Factor-α

Abstract

Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS.

NOX Modifiers—Just a Step Away from Application in the Therapy of Airway Inflammation?

“…Together, the assembly of this complex forms the functional NOX2 enzyme. NOX2 isoforms are ubiquitously expressed, and they are present in the lungs endogenously in the steady state and are overabundant during inflammatory conditions (16,30,60,156). The main NOX2-expressing cell types within the respiratory tract include alveolar macrophages, dendritic cells, and/or other resident or infiltrated inflammatory-immune cells (e.g., neutrophils, eosinophils, and lymphocytes) ( Fig.…”

Effect of postharvest handling practices on phytochemical concentrations and bioactive potential in wild blueberry fruit

“…However, other studies imply that processing techniques may have little influence on oxygen radical absorbance capacity [16]. It has been established that 5 g/ml of crude WBB extract significantly decreases the level of induced reactive oxygen species in SH-SY5Y cells [26]. Additionally, crude WBB extract does not compromise SH-SY5Y cell viability up to 75 g/ml [27].…”

Protective effect of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide, a novel unsymmetrical divinyl sulfide, on an oxidative stress model induced by sodium nitroprusside in mouse brain: involvement of glutathione peroxidase activity

“…Therefore, the novelty of this study was to demonstrate the antioxidant effect of a novel divinyl sulfide compound on an in‐vivo model of oxidative stress. In addition, ((4‐ tert ‐butylcyclohexylidene) methyl) (4‐methoxystyryl) sulfide is a non‐polar compound and other studies have demonstrated that non‐polar agents showed higher cerebral antioxidant effect than polar ones [54,55]…”

“…In addition, ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide is a non-polar compound and other studies have demonstrated that non-polar agents showed higher cerebral antioxidant effect than polar ones. [54,55] The exact mechanism to explain the antioxidant action of sulfide is not clear at the moment. However, we can speculate that this compound acts on different antioxidant defence mechanisms, which was clearly demonstrated by the efficiency of this compound in restoring the cerebral oxidative damage induced by SNP.…”