Quinacrine Mitigates LPS-Induced Neuroinflammation in Rats via Modulation of the TLR4/NF-κB Axis, Astrocyte Activation (GFAP), and Oxidative Stress.

Neuroinflammation is a fundamental pathophysiological mechanism underlying various neurodegenerative diseases. This study investigated the therapeutic effects of quinacrine (QC), a phospholipase A2 (PLA2) inhibitor, in lipopolysaccharide (LPS)-induced neuroinflammation. Thirty-five male Sprague-Dawley rats were divided into five groups: control, QC alone, LPS, LPS + QC 10 mg/kg, and LPS + QC 30 mg/kg. QC was administered intraperitoneally for three consecutive days. LPS was administered two hours after the final QC dose, and the animals were euthanised six hours later. ELISA analyses revealed significant increases in IL-1β, IL-6, and PLA2 levels following LPS administration; however, QC pretreatment reduced these increases in a dose-dependent manner. Anti-inflammatory IL-10 levels were enhanced with QC pretreatment. The fact that QC is a direct PLA2 inhibitor is consistent with this mechanism. LPS increased MDA levels and decreased antioxidants such as GSH, GPx, CAT, and SOD. QC pretreatment normalized these parameters and reduced oxidative damage. LPS caused a significant drop in BDNF levels. Expressions of COX2, iNOS, and GFAP were notably increased in the LPS group, while pretreatment with QC pretreatment at 30 mg/kg significantly lowered these glial and inflammatory markers. Western blot results showed that LPS-activated TLR4 and NF-κB protein levels were reduced dose-dependent manner by QC pretreatment. Overall, our results suggest that QC suppresses the proinflammatory response, decreases oxidative stress, and promotes neuroplasticity by targeting multiple pathways in the LPS-induced neuroinflammation model.