Exploration of the In Vitro and In Vivo Neuroprotective Effects of Several Polyphenolics on LPS‐Induced Neuroinflammation

Oxidative stress and neuroinflammation are key components in neurodegenerative diseases, where early intervention using natural treatments may offer neuroprotective effects. This study shows that isoliquiritigenin (ISL), hesperidin (HES), and curcumin (CUR) can mitigate lipopolysaccharide (LPS)‐induced neuroinflammation and oxidative stress in vitro and in vivo. The compounds were initially tested for cytotoxicity and found to reduce nitric oxide (NO) production, especially CUR and ISL. They were able to restore antioxidant enzyme activities both in vivo and in vitro. All treatments reduced inducible nitric oxide synthase (iNOS) expression compared to the untreated LPS control group. Behavioral assessments indicated that LPS impaired spatial and nonspatial memory, but treatments improved cognitive performance. Biomarker analyses revealed that ISL, HES, and CUR reduced the interleukin (IL)‐1β and nuclear factor erythroid 2‐related factor 2 (Nrf2) ratio in the hippocampus. Moreover, they decreased the level of caspase‐3 demonstrated by western blotting and tumor necrosis factor‐α (TNF‐α) level. Thereby they inhibited LPS elicited apoptosis. Likewise, their anti‐inflammatory effects were illustrated in the histopathological examination. Furthermore, they decreased the expression of amyloid‐β. The study reinforces the potential of these natural compounds as protective and therapeutic cost‐effective alternatives for managing neuroinflammation and neurodegeneration.