Fisetin provides neuroprotection in pentylenetetrazole-induced cognition impairment by upregulating CREB/BDNF

Objectives: Fisetin is a flavonoid molecule known to be neuroprotective by its multiple mechanisms. The present study was designed to explore the effect of fisetin in the pentylenetetrazole (PTZ) kindling-induced cognitive dysfunction in mice.Methods: Kindling was established by the intraperitoneal administration of PTZ in a subconvulsive dose (25 mg/ kg). Mice were administered fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable cognition-enhancing effect. The kindled mice were evaluated for cognition using behavioral tests-elevated plus maze and passive avoidance response. Then, the oxidative stress markers, gene expressions and neurotransmitters levels were estimated in the hippocampus and cortex of mice.Results: Passive avoidance response and elevated plus maze paradigms showed that fisetin administration improved the cognitive function in kindled mice. The increased levels of lipid peroxidation and protein carbonyl were modulated upon fisetin administration through increasing the levels of antioxidants (reduced glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase) in the hippocampus and cortex of kindled mice. Upregulated gene expressions of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were observed in the hippocampus and cortex of fisetin-administered mice which play a crucial role in cognitive function. Furthermore, alterations of neurotransmitter levels (dopamine, GABA, and glutamate) and acetylcholinesterase (AchE) were ameliorated by fisetin administration in the hippocampus and cortex of kindled mice. Conclusion: Our findings suggest a therapeutic potential of fisetin against cognitive dysfunction associated with PTZ-induced kindling.

Automated summary

Fisetin has been found to improve cognitive function in mice with PTZ-induced kindling through modulation of oxidative stress markers, gene expressions, and neurotransmitter levels. These findings suggest a therapeutic potential of fisetin against cognitive dysfunction associated with PTZ-induced kindling.