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.