Alleviated Neuroinflammation and Increased Neuritogenesis by Palmitic Acid from Cissus quadrangularis

Neuroinflammation and altered neurite outgrowth are pivotal pathological characteristic features of neurodegenerative disorders. Our research aims to explore the potential anti-neuroinflammatory activity of palmitic acid derived from Cissus quadrangularis. Our results reveal that palmitic acid at low concentrations significantly attenuates neuroinflammation in Neuro-2a cells by suppressing the expression of TNF-α and RhoA GTPase. Palmitic acid also modulates the activity of the small GTPase RhoA, a crucial regulator of cytoskeletal dynamics, thereby facilitating cytoskeletal rearrangements essential for neurite outgrowth. Our study also identifies those low concentrations of palmitic acid have a positive regulatory influence on cellular prion protein (PrP^C) and reelin, which are known for their roles in neuronal migration, differentiation, and synaptic plasticity. It maintains optimal neurite formation in LPS + PA (1 ng/ml)-Neuro-2a cells compared to LPS-treated cells, demonstrating a dose-dependent promotion of neurite extensions and branching. In conclusion, our findings elucidate the molecular pathways that palmitic acid exhibits anti-neuroinflammatory activity, highlighting its potential as a regulatory molecule at low concentrations under neuroinflammation. The palmitic acid modulates the functional activities of Rho small GTPases, and their regulation by transmembrane proteins, PrP^C, and reelin under neuroinflammation contribute to the optimum neurite outgrowth in the neurons.