Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active
pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological
actions including antioxidant, anti-inflammatory, cholesterol-lowering effect, and inhibition
of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and
brain drug uptake. The present study is directed for the formulation and characterization of Chitosan
BBR-Nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine
induced cognitive impairments.
Methods: BBR-NPs were formulated using the ionic gelation method, and tripolyphosphate was
chosen as a crosslinker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing
profile were estimated. To investigate the neuroprotective effects, adult fifty-six Wistar male rats
were randomly distributed into three control groups, received saline, polyethylene glycol or Chitosan-
NPs, respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated
groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/
kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris
water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates, as
well as neuroplasticity markers and histopathological examination were assessed.
Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were
powerful inhibitory ligands towards AChE and Aβ42 formation and significantly down-regulated
Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of
BBR therapeutic recommended dose, significantly improved learning and memory function. This
could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the
improvement of the neuroplasticity markers.
Conclusion: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability,
absorption and brain drug uptake, which need more investigation in future work.