Centella asiatica suppresses inflammation and apoptosis and regulates the Gsk-3β signaling pathway in aluminum chloride-induced neurodegeneration in rats

Over 50 million people worldwide are affected by neurodegenerative diseases, and finding effective treatments is crucial. Centella asiatica (CA) is a regenerating herbal medicine rich in triterpenes and phenolic compounds, traditionally used to stimulate memory. CA extract possesses antioxidant and anti-inflammatory properties. Therefore, we aimed to elucidate the underlying molecular mechanisms of CA extract as a neuroprotector against AlCl3-induced neurodegeneration in rats. Forty-eight rats were categorized into eight groups. The control group administered distilled water, whereas the aluminum (Al) group received aluminum chloride (AlCl3) at 100 mg/kg. Three supplementary groups received Centella asiatica (CA) at (200, 400, and 600 mg/kg). Three more groups were administered both CA and AlCl3. All treatments were administered orally over 5 weeks. Oxidative stress biomarkers (MDA, GSH, and SOD) and DNA damage extent were measured in the brain tissues. In addition, the mRNA expression of apoptotic and inflammatory genes (Bax/Bcl2, Caspase3, Il-1β, Gsk3β) and immunohistochemical staining of B-amyloid and tau protein were evaluated. The CA extract improved oxidative stress response by raising the levels of GSH and SOD while diminishing the MDA levels and DNA damage parameters. It also reduced the expression of genes responsible for inflammation and apoptosis. CA decreased the accumulation of both B-amyloid and tau proteins in the brain tissue. Further, the histopathological examination of brain tissues revealed a significant improvement in the CA-pretreated groups. CA effectively reduced aluminum chloride neurotoxicity by decreasing apoptotic and inflammatory gene expression and lowering Gsk-3β levels, which helps minimize brain amyloid-beta and tau protein accumulation.