Effects of <i>Luffa cylindrica</i> (L.) Roem Extract on Microglial Activation-Mediated Mild Cognitive Impairment via Regulation of CREB Signaling Pathway

Neuroinflammation is increasingly recognized as a pivotal contributor to mild cognitive impairment (MCI), with microglial activation playing a central role in this process. While <i>Luffa cylindrica</i> (L.) Roem is known for its anti-inflammatory properties, its effects on MCI and its active components have not been fully elucidated. In this study, we evaluated the anti-inflammatory and neuroprotective effects of <i>Luffa cylindrica</i> extract (LCE) on microglial activation and MCI-like behaviors induced by lipopolysaccharide (LPS). BV2 microglial cells were stimulated with LPS (1 μg/ml) and treated with LCE (25, 50, or 100 μg/ml). Microglial activation was assessed via Griess assay, western blotting, RT-PCR, and ELISA. <i>In vivo</i>, male ICR mice were received LCE (50 or 300 mg/kg) orally for 7 days in combination with intraperitoneal LPS (0.5 mg/kg). Cognitive function was evaluated using passive avoidance and Y-maze tests. The hippocampus was harvested for biochemical analysis. High-performance liquid chromatography (HPLC) was used to identify major bioactive components of LCE. LCE treatment significantly reduced the production of nitric oxide (NO), pro-inflammatory cytokine expression, and inflammation-associated protein levels in BV2 cells. These effects were associated with inhibition of the AKT-GSK3β-CREB signaling pathway. <i>In vivo</i>, oral LCE administration ameliorated LPS-induced cognitive impairment and decreased inflammatory markers in the hippocampus. HPLC analysis identified myricetin as a major component of LCE, which independently exhibited anti-inflammatory effects in microglia. These findings highlight the potential of LCE as a natural therapeutic agent for neuroinflammation-related cognitive impairment, with myricetin contributing to its pharmacological activity.