Self-assembled low molecular weight chitosan-bilobalide microsuspension protects hippocampal toxicity in amyloid beta(25–35) induced mice

Alzheimer's disease (AD) is a progressive neurological disorder and is characterized by the accumulation of amyloid beta (Aβ) peptide and hyperphosphorylated tau as a pathological hallmark. Bilobalide (BB) being a highly hydrophobic compound, has poor aqueous solubility, stability, and brain bioavailability. In the present study, we prepared self-assembled low molecular weight chitosan-bilobalide microsuspension (BBC) and examined its neuroprotective effect against intracerebroventricular induction of Aβ_(25–35) toxicity in mice. Results showed that BBC has a particle size of 5.77 µm with a desired zeta potential of +42.2 ± 2 mV. BBC displayed aqueous solubility with sustained release kinetics in vitro and had better intracellular transport (70 %) of BB from BBC in Caco-2 cells. Further, treatment with BBC showed increased content [BBC (10 mg), 83.4 ng; BB (10 mg), 15.8 ng] of BB in brain and alleviated Aβ_(25–35) induced memory impairment in mice. Moreover, BBC diminished oxidative stress, neuroinflammation, and synaptic dysfunction in Aβ_(25–35) induced AD model. In addition, our western blot data suggested that treatment with BBC ameliorated Aβ_(25–35) induced hyperphosphorylation of tau protein through regulation of aberrant phosphorylation of Akt/GSK3β/MAPK pathway. The current study may confirm the application of BBC as an oral supplement in the food and pharmaceutical industries for AD conditions.