Berberine Nanoencapsulation Attenuates Hallmarks Of Scoplomine Induced Alzheimer'S-Like Disease In Rats

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 A beta 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 Chito san-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-beta 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 A beta 42 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-beta 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.