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Pharmacological implications of ipriflavone against environmental metal-induced neurodegeneration and dementia in rats.
| Environmental Science and Pollution Research | Hussien HM, Ghareeb DA, Ahmed HEA, Hafez HS, Saleh SR. | [Epub ahead of print]
Amyloid plaques Dementia Protective effect Brain Cognitive Function Genetics Mechanisms of Cellular Toxicity Oxidative Stress Susceptible Populations Animal Study

Abstract

Long-term exposure to environmental neurotoxic metals is implicated in the induction of dementia and cognitive decline. The present study aims to illustrate the therapeutic role of ipriflavone as a synthetic isoflavone against environmental metal–induced cognitive impairment in rats. Dementia was induced by a mixture of aluminum, cadmium, and fluoride for 90 days followed by ipriflavone for a further 30 days.  Metal-treated animals exhibited abnormal behaviors in the Morris water maze task. Neuropathological biomarkers including oxidative stress (TBARS, NO, SOD, GPX, GST, and GSH), inflammation (TNF- ?, IL-6, and IL-1?), neurotransmission (AChE and MAO), and insulin resistance (insulin, insulin receptor, and insulin-degrading enzyme) were altered, which consequently elevated the level of amyloid-?42 and tau protein in the hippocampus tissues inducing neuronal injury. Ipriflavone significantly (P < 0.05) ameliorated the neurobehavioral abnormalities and the cognitive dysfunction biomarkers via antioxidant/anti-inflammatory mechanism. Moreover, ipriflavone downregulated the mRNA expression level of amyloid precursor protein and tau protein, preventing amyloid plaques and neurofibrillary tangle aggregation at P < 0.05. A molecular docking study revealed that ipriflavone has a potent binding affinity towards AChE more than donepezil and acts as a strong AChE inhibitor. Our data concluded that the therapeutic potential of ipriflavone against dementia could provide a new strategy in AD treatment.

*Original abstract online at https://link.springer.com/article/10.1007/s11356-021-15193-7

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Affiliations

  1. Department of Pharmacology and Therapeutics Department, Faculty of Pharmacy, Pharos University, Canal El Mahmoudia Street, Smouha, Sidi Gaber, P.O. Box 37, Alexandria, Egypt

    Hend M. Hussien

  2. Biological Screening and Preclinical Trial Laboratory, Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt

    Doaa A. Ghareeb & Samar R. Saleh

  3. Center of Excellency for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industries Development Centre (PFIDC), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, Egypt

    Doaa A. Ghareeb & Samar R. Saleh

  4. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, 11884, Egypt

    Hany E. A. Ahmed

  5. Zoology Department, Faculty of Science, Suez University, Suez, Egypt

    Hani S. Hafez

Contributions

Hend Mohamed Hussien: participated in practical work, wrote the first manuscript, and approved the final manuscript. Doaa A. Ghareeb: conceptualized research idea design, shared in practical work, and revised the manuscript. Hany E. A. Ahmed: conducted molecular modelling and docking study. Hani S. Hafez: conducted statistical analysis. Samar R. Saleh: participated in the practical part and writing of the manuscript.

Corresponding author

Correspondence to Hend M. Hussien.

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The experiments were carried out according to the ethical guidelines of Institutional Animal Care & Use Committee, Pharmaceutical and Fermentation Industries Development Centre, City of Scientific Research and Technological Applications (SRTA-City), Borg Al-Arab, Alexandria, Egypt (IACUCCs)/IACUA#16-1P/7020), and followed the National Institutes of Health (NIH).

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Keywords

  • Dementia
  • Ipriflavone
  • Heavy and trace metals
  • Oxidative stress and neuroinflammation
  • Insulin resistance
  • Amyloid-?40/42 and tau protein