Natural inhibitors for acetylcholinesterase and autophagy modulators as effective antagonists for tau and β-amyloid in Alzheimer’s rat model

Abstract

Background: Phytochemicals have amazing biological effects in relation to age-related illnesses and are increasingly being studied in clinical trials. The goal of this study was to examine the effectiveness of the aqueous extracts of Rosmarinus officinalis L. (Rosemary) and Crocus sativus L. (Saffron) and their combinations as tau and β-amyloid antagonists in an Alzheimer’s rat model. Methods: AlCl₃ and D-galactose (150 & 300 mg/kg) were used to create the Alzheimer’s neuroinflammation rat model. The animals were subsequently given the two extracts and their combinations (500 mg/kg) along 15 days. The cognitive impairment, oxidative stress, tau & amyloid neuroproteins, acetylcholine, acetylcholinesterase neurotransmitters, proinflammatory cytokines, LC3 as an autophagy marker, computational analysis, and morphological alterations were all assessed. Results: When compared to the conventional donepezil and normal groups, the treated groups showed a significant improvement in all calculated parameters. The cortex and hippocampus have a better morphological appearance. In silico analysis found that these extracts may have an affinity for and impede the activity of some proteins thought to be essential regulators of disease progression. Conclusion: Rosemary and Saffron extracts by the power of their constituents were able to alleviate the neurotoxicity of AlCl₃ & D-galactose and regulate the natural autophagy process.

Graphic Abstract

Keywords:

• Tau protein
• β-amyloid
• acetylcholinesterase
• autophagy
• rosemary
• saffron

Acknowledgments

The authors would like to express their gratitude to Dr. Mahmoud El-Sherbiny at NRC for his kind support.

Ethics approval

Animal materials and experimental procedures were approved by the animal care and use ethical committee of, Minia University (No. ES16/2020) and performed in compliance with the NIH Guide for the care and use of laboratory animals.

Author contribution

S.A.H. and H.I. study conception and design, interpretation of results and writing original draft. M.H. performed most of the experiments. O.H. performed pathological analysis. A.E. performed In silico study. O.O. provided assistance for colorimetric experiments and data analysis. H.I. and M.H. collection of data and statistical analysis. The final version of the manuscript has been read and approved by all authors.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Availability of data and materials

Available upon request.