Nanoformulated fisetin ameliorates Alzheimer's disease via reducing proinflammatory cytokines and activating the NRF2/HO-1 pathway

Nov 18, 2024Nanomedicine (London, England)

Nanoformulated fisetin may improve Alzheimer's by lowering brain inflammation and boosting cell protection pathways

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Abstract

Treatment with a fisetin nanoformulation (5 mg/kg/day) over 21 days significantly improved neurobehavioral outcomes in a mouse model of Alzheimer's disease.

Fisetin nanoformulation reduced memory impairment, motor deficits, and depression-like symptoms caused by Aβ.
Decreased levels of oxidative and nitrosative stress were observed in the cortex, hippocampus, and colon.
Pro-inflammatory cytokine levels were also reduced in the brain and colon tissues.
Histological analyses indicated improved tissue architecture in both brain and colon following treatment.
The nanoformulation may enhance fisetin's pharmacokinetics, contributing to its neuroprotective effects.

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The study aimed to evaluate the neuroprotective effect of a chitosan-coated fisetin nanoformulation in an experimental Alzheimer's disease (AD) model, focusing on improving fisetin's pharmacokinetics and exploring its impact on both brain and colon pathology.AD was induced in mice by intracerebroventricular administration of Aβ. Mice were treated with either fisetin or a fisetin nanoformulation (5 mg/kg/day, orally) for 21 days. Behavioural assessments were conducted to evaluate memory impairment, motor deficits, and depression-like behaviour. Oxidative stress markers and pro-inflammatory cytokines were measured in the cortex, hippocampus and colon. The changes in cortical and hippocampal AChE levels were also recorded. Histological studies were performed on the cortex, hippocampus (dentate gyrus), and proximal colon.The fisetin nanoformulation significantly improved neurobehavioral outcomes, reducing memory impairment, motor deficits and depression-like symptoms induced by Aβ. It also decreased oxidative and nitrosative stress, along with pro-inflammatory cytokine levels in the cortex, hippocampus and colon. Histological analyses revealed improved brain and colon tissue architecture after treatment with the nanoformulation.The chitosan-coated fisetin nanoformulation enhanced the neuroprotective effects of fisetin in an AD model, likely by improving its pharmacokinetic profile. The findings also suggest a potential link between colon health and Aβ-induced AD pathology, underscoring the therapeutic potential of fisetin nanoformulations in AD management. Aim: Materials & methods: Results: Conclusion: 1-42 1-42

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Nanoformulated fisetin ameliorates Alzheimer's disease via reducing proinflammatory cytokines and activating the NRF2/HO-1 pathway

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