Naringenin Ameliorates LPS-Induced Neuroinflammation Through NF-κB Signaling in Human Microglia and Protects Neuronal Cells

Background: Engagement of the NF-κB signaling pathway is crucial for controlling immune and inflammatory gene expression within the central nervous system (CNS). Naringenin, a flavonoid derived from citrus fruits, is known for its anti-inflammatory and antioxidant effects; however, its impact on LPS-induced neuroinflammation in HMC3 (human microglial) and SH-SY5Y (neuronal) cell lines has not been thoroughly studied. Objectives: We sought to ascertain the neuroprotective role of Naringenin in LPS-induced neuroinflammation in microglia and neuronal cell lines with a focus on modulation of the NF-κB signaling pathway. Methods: LPS treatment was given to HMC3 cells to induce an inflammatory response, besides the secretome of HMC3 cells was transfered to SH-SY5Y cells with the administration of Naringenin. A cell viability assay, ROS level measurements, Western blotting, and immunocytochemistry were employed to quantify and localize NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Nuclear fractions of NF-κB were analyzed to screen its activation and translocation. Results: Naringenin treatment led to a dose-dependent decrease in LPS-induced reactive oxygen species (ROS) production. It significantly reduced the expression of pro-inflammatory cytokines and inhibited NF-κB activation in HMC3 cells. The nuclear translocation of NF-κB was notably diminished after treatment, as demonstrated by both Western blot and immunocytochemistry. These results suggest that Naringenin exerts an anti-inflammatory effect by suppressing the NF-κB signaling pathway. Conclusions: The findings suggest the potential therapeutic role of Naringenin using in vitro models in mitigating neuroinflammation through modulation of the NF-κB signaling pathway.