Honokiol alleviates oxidative stress, neuroinflammation, and apoptosis in excitotoxicity induced by ouabain, a...

Excitotoxicity, oxidative stress, and neuroinflammation play significant roles in the pathophysiology of neurodegenerative disorders. This study aims to examine the impact of honokiol (HNK) on antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in a model of excitotoxicity induced by intracerebroventricular (icv) ouabain (OUA) in rats. Rats were allocated to five equal groups (n = 10): (I) Animals given intraperitoneal isotonic saline solution for seven days (Control); (II) animals given a single dose of 5 μl OUA solvent (artificial cerebrospinal fluid-icv) on the first day (Sham); (III) animals given a single dose of OUA (5 μl at a concentration of 10⁻³ M-icv) (OUA); (IV) Animals given HNK for seven days (HNK); (V) animals given OUA and then HNK for seven days (OUA+HNK). OUA administration caused an increase in cerebral cortex malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels and a decrease in glutathione (GSH) and superoxide dismutase (SOD) levels. The OUA injection resulted in a decrease in immobility in the forced swim test, an increase in swimming and climbing activities, and a decrease in Na + /K + -ATPase enzyme activity. Significant improvements in oxidative stress markers and tissue antioxidant levels were detected with HNK treatment. Additionally, HNK treatment inhibited apoptotic processes by increasing Heat Shock Protein-70 (HSP-70) and suppressing the expression of the pro-apoptotic protein Bax. Furthermore, histopathological changes caused by OUA administration were found to improve in the HNK-treated groups. In conclusion, our findings suggest that HNK therapy, by reducing oxidative tissue damage, apoptosis, and inflammation, may be a promising adjunctive treatment for pathologies presenting with excitotoxicity.