Effect of icariin in a rat model of colchicine-induced cognitive deficit: role of β-amyloid proteolytic enzymes

ABSTRACT

The deposition of β-amyloid plaques, either due to their over-production or insufficient clearance, is an important pathological process in cognitive impairment and dementia. Icariin (ICA), a flavonoid compound extracted from Epimedium, has recently gained attention for numerous age-related diseases, such as neurodegenerative diseases. We aimed to explore the possible neuro-protective effect of ICA supplementation in colchicine-induced cognitive deficit rat model and exploring its effect on the β-amyloid proteolytic enzymes. The study included four groups (10 rats each): normal control, untreated colchicine, colchicine + 10 mg/kg ICA, and colchicine + 30 mg/ kg ICA. Results revealed that intra-cerebro-ventricular colchicine injection produced neuronal morphological damage, β amyloid deposition, and evident cognitive impairment in the behavioral assessment. Icariin supplementation in the two doses for 21 days attenuated neuronal death, reduced the β amyloid levels, and improved memory consolidation. This was associated with modulation of the proteolytic enzymes (Neprilysin, Matrix Metalloproteinase-2, and insulin-degrading enzyme) concluding that β-amyloid enzymatic degradation may be the possible therapeutic target for ICA.

KEYWORDS:

• Icariin
• neprilysin
• insulin-degrading enzyme
• matrix metalloprotinase-2

Abbreviations:

• AD: Alzheimer’s disease
• ACSF: artificial cerebrospinal fluid
• ECM: extracellular matrix
• ICA: Icariin
• IDE: insulin-degrading enzyme
• ICV: intra-cerebro-ventricular
• MMP: matrix metalloproteinase
• NEP: neprilysin
• Aβ: β amyloid
• NF-κB: Nuclear factor-kappa B

Acknowledgements

The authors thank medical physiology department, faculty of medicine for providing the study animals and supporting their housing, Clinical Pharmacology Department, Faculty of Medicine for preparation of the drugs, Medical Biochemistry Department, Faculty of Medicine for biochemical assessment and Histology and Cell Biology Department for histological examination. Author contributions: E.M.O. and E.A.A. designed the study. E.M.O., E.A.A. and S. E. performed the experiment and collected data. A.M.O., S. E. and N.A.S. analyzed the data. All authors interpreted data. A.M.O. N.A.S. prepared figures. E.M.O. and E.A.A. drafted the manuscript. All authors critically revised the manuscript. All authors read and approved the final version of manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the finding of the study are available on request from the corresponding author.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Notes on contributors

Eman M. Omar

Eman M. Omar is a lecturer in the Department of Medical Physiology, Faculty of Medicine, Alexandria University, Egypt.

Soha Elatrebi

Soha Elatrebi is a lecturer in the Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Egypt.

Nada A. H. Soliman

Nada A.H. Solimanis is a lecturer in the Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Egypt.

Amira M. Omar

Amira M. Omar is a lecturer in the Department of Histology & Cell Biology, Faculty of Medicine, Alexandria University, Egypt.

Eman A. Allam

Eman A. Allam is a lecturer in the Department of Medical Physiology, Faculty of Medicine, Alexandria University, Egypt.