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Berberine Nanoencapsulation Attenuates Hallmarks of Scoplomine Induced Alzheimer's-Like Disease in Rats

[ Vol. 15 , Issue. ]

Author(s):

Samar R. Saleh, Mariam M. Abady, Mohammed Nofal, Nashwa W. Yassa, Mohamed S. Abdel-latif, Mohamed Ismail Nounou*, Doaa A. Ghareeb and Nihad Abdel-Monaem Pages 1-16 (16)

Abstract:


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, antiinflammatory, 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 ionic gelation method and tripolyphosphate was chosen as a cross linker. 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 toward 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.

Conclusions: 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.

Keywords:

Scopolamine, Acetylcholinesterase, Berberine, Oxidative stress, Amyloid-β, Morris water maze test, Neuroplasticity, Chitosan

Affiliation:

Biochemistry Department, Faculty of Science, Alexandria University, P.O. Box 21511, Alexandria, Biochemistry Department, Faculty of Science, Alexandria University, P.O. Box 21511, Alexandria, Institute of graduate studies and research, Alexandria university, Biochemistry Department, Faculty of Science, Alexandria University, P.O. Box 21511, Alexandria, Medical laboratory technology department, Allied medical sciences, Pharos University, Department of Pharmaceutical Sciences (DPS), School of Pharmacy and Physician Assistant Studies (SOPPAS), University of Saint Joseph (USJ), Hartford, CT 06103, Biochemistry Department, Faculty of Science, Alexandria University, P.O. Box 21511, Alexandria, Biochemistry Department, Faculty of Science, Alexandria University, P.O. Box 21511, Alexandria



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