Neuroprotective Role of Gnidiol in Attenuating Oxidative Stress and Microglial Activation in LPS-Induced Neuroinflammation Models

Abstract

Neuroinflammation and oxidative stress are pivotal contributors to the progression of neurodegenerative diseases. This study investigated the neuroprotective potential of Gnidiol, a diterpenoid compound, in LPS-induced in vitro models of neuroinflammation using murine BV-2 microglial and human SH-SY5Y neuroblastoma cell lines. Treatment with lipopolysaccharide (1 µg/mL) significantly reduced cell viability, elevated reactive oxygen species (ROS), and increased the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) along with microglial activation markers such as Iba1 and NF-κB. Pre-treatment with Gnidiol (1–25 µM) restored cell viability in a concentration-dependent manner and markedly reduced ROS levels and cytokine production. Immunocytochemical analysis revealed that Gnidiol suppressed NF-κB nuclear translocation and downregulated Iba1 expression, indicating a direct anti-inflammatory effect on activated microglia. The data suggest that Gnidiol exerts dual protective effects through attenuation of oxidative stress and inhibition of inflammatory signalling pathways. These findings support the therapeutic potential of Gnidiol as a neuroprotective agent and a candidate for further preclinical evaluation in neurodegenerative disease models characterized by chronic inflammation and oxidative stress.