Honokiol alleviates oxidative stress, neuroinflammation, and apoptosis in excitotoxicity induced by ouabain, a Na + /K + -ATPase inhibitor.

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.