Fisetin nanosuspension: potential inhibitor of monoamine oxidase in Aβ(25-35) induced mice

The key pathological hallmarks of Alzheimer's disease (AD) include extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles. Fisetin, a neuroprotective antioxidant, is widely consumed through fruits and vegetables but has low bioavailability, poor solubility and high metabolism, limiting its therapeutic potential. This study aimed to develop a fisetin nanosuspension to improve its bioavailability and neuroprotective effects in Aβ(25-35) induced dementia mice. The nanosuspension was prepared by nanoprecipitation method and characterised. For in vivo study, mice were treated with 10 and 20 mg/kg of fisetin or 10 mg/kg fisetin nanosuspension daily for 21 days, followed by intracerebroventricular Aβ(25-35) injection (ICV)on day 15. Memory and learning tests were conducted on day 20, and biochemical analyses were performed on brain tissues. The nanosuspension had an average particle size of 225.4 ± 2.95 nm, polydispersity index (PDI) of 0.19 and zeta potential of -19.13 ± 1.17 mV. In vivoresults showed significant memory and learning improvement (P < 0.01) and reduced monoamine oxidase-A (MAO-A) levels (P < 0.01), -induced amnesia. The fisetin nanosuspension effectively enhanced oral bioavailability and inhibited MAO-A activity, presenting a promising approach for future AD drug development.