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Flavonoids and Alzheimer’s disease: reviewing the evidence for neuroprotective potential

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Abstract

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public’s health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer’s disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease’s course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

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Abbreviations

NDDs:

Neurodegenerative disorders

AD:

Alzheimer’s disease

NO:

Nitric oxide

TNF-α:

Tumor necrosis factor alpha

OS:

Oxidative stress

APP:

Amyloid precursor protein

Aβ:

Amyloid-beta

PS1:

Presenilin 1

PS2:

Presenilin 2

PET:

Positron emission tomography

CSF:

Cerebrospinal fluid

NFTs:

Neurofibrillary tangles

Ach:

Acetylcholine

APOE:

Apolipoprotein E

APOJ:

Apolipoprotein J

SORL:

Sortilin-related receptor L

IL-6:

Interleukin-6

GM:

Gut microbiota

HF:

Hawthorn flavonoid

AβO:

Amyloid-β oligomers

BDNF:

Brain-derived neurotrophic factors

PTP1B:

Potent protein-tyrosine phosphatase 1B

STZ:

Streptozotocin

N2a:

Neuro-2a

BACE1:

β-Site amyloid precursor protein-cleaving enzyme 1

NF-κB:

Nuclear factor-κB

MAPKs:

Mitogen-activated protein kinases

LPS:

Lipopolysaccharide

NOD2:

Nucleotide oligomerization domain protein 2

MMP:

Mitochondrial membrane potential

RIP2:

Receptor-interacting protein 2

6-OHDA:

6-Hydroxydopamine

CH:

Catechin hydrate

EGCG:

Epigallocatechin-3-gallate

TH:

Tyrosine hydroxylase

Non-Tg:

Non-transgenic

MAO-A:

Monoamine oxidase-A

ROS:

Reactive oxygen species

C3G:

Cyanidin-3-glucoside

ER:

Estrogen receptor

AChE:

Acetylcholinesterase

MAPs:

Microtubule-associated proteins

TAI:

Tau aggregation inhibitor

MTC:

Methylthioninium chloride

HMG-CoA:

Hydroxymethylglutaryl-CoA

MCI:

Mild cognitive impairment

MMSE:

Mini-Mental State Examination

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Acknowledgements

The authors are thankful to the Deanship of Scientific Research, King Khalid University, Abha, Saudi Arabia, for financially supporting this work through the Large Research Group Project under Grant no. R.G.P.2/557/44.

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The authors received no external funding.

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Author notes

  1. Md. Al Amin and Mohamed H. Nafady have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh

    Md. Al Amin, Tahmina Afroz & Talha Bin Emran

  2. Laboratory of Agro-Biotechnology and Nutrition in Semi-Arid Zones, Faculty of Nature and Life Sciences, University of Ibn Khaldoun, Tiaret, Algeria

    Zerrouki Dehbia

  3. Faculty of Applied Health Science Technology, Misr University for Science and Technology, Giza, 12568, Egypt

    Mohamed H. Nafady

  4. Department of Clinical Pharmacy, College of Dentistry & Pharmacy, Buraydah Private Colleges, Buraydah, 51418, Saudi Arabia

    Mehrukh Zehravi

  5. Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University (DPSRU), Govt. of N.C.T. of Delhi, Pushpvihar, New Delhi, 110017, India

    Kusuma Pravin Kumar

  6. Department of Pharmaceutical Analysis, School of Pharmacy, Anurag University, Ghatkesar, Hyderabad, 500088, India

    M. Akiful Haque

  7. Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Aurangabad, 431001, India

    Mirza Shahed Baig

  8. Department of Pharmacology, School of Pharmacy, Anurag University, Hyderabad, TS, India

    Azmath Farhana

  9. Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa, 413520, Maharashtra, India

    Sharuk L. Khan

  10. Department of Biology, Faculty of Nature and Life Sciences, University of Ibn Khaldoun, Tiaret, Algeria

    Doukani Koula

  11. Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, 90123, Italy

    Marco Tutone

  12. Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia

    Firzan Nainu

  13. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia

    Irfan Ahmad

  14. Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI, 02912, USA

    Talha Bin Emran

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  1. Md. Al Amin
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Al Amin, M., Dehbia, Z., Nafady, M.H. et al. Flavonoids and Alzheimer’s disease: reviewing the evidence for neuroprotective potential. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-023-04922-w

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