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Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights

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Abstract

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aβ) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects.

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Abbreviations

AD :

Alzheimer's disease

NFTs :

Neurofibrillary tangles

Aβ :

Amyloid-beta

AGEs :

Advanced glycation end products

APP :

Amyloid precursor protein

BACE1 :

Beta-secretase 1

DM :

Diabetes mellitus

SIRT1 :

Silent information regulator T1

ROS :

Reactive oxygen species

BBB :

Blood–brain barrier

LRP1 :

Low-density lipoprotein receptor-related protein 1

ABC :

ATP Binding Cassette transporter

IDE :

Insulin-degrading enzyme

IGF :

Insulin-like growth factor

IRS-1 :

Insulin receptor substrate 1

GSK-3β :

Glycogen synthase kinase 3 beta

CAT :

Catalase

SOD :

Superoxide dismutase

GSH :

Glutathione

MDA :

Malondialdehyde

GPx :

Glutathione peroxidase

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Acknowledgements

We are grateful to the office of the Vice-Chancellor for Research and Technology at Tabriz University of Medical Sciences for supporting further research.

Funding

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

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Authors and Affiliations

  1. Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Sarvin Sanaie, Mostafa Araj-Khodaei & Mohammad Hossein Ayati

  2. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Saba Nikanfar

  3. Research Center of Psychiatry and Behavioral Sciences, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Zahra Yousefi Kalekhane

  4. Department of Psychology, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran

    Zahra Yousefi Kalekhane

  5. Student Research Committee, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Akbar Azizi-Zeinalhajlou

  6. Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Akbar Azizi-Zeinalhajlou

  7. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Saeed Sadigh-Eteghad

  8. Department of Persian Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Mostafa Araj-Khodaei

  9. Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Hossein Ayati

  10. Research Unit of Clinical Physiology and Nuclear Medicine, Department of Clinical Research, Odense University Hospital, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

    Sasan Andalib

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  1. Sarvin Sanaie
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  2. Saba Nikanfar
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Contributions

Sarvin Sanaie: Conceptualization, Data interpretation; Saba Nikanfar: Writing- Original draft preparation, Data analysis; Zahra Yousefi Kalekhane: Investigation, Data search and extraction; Akbar Azizi-Zeinalhajlou: Data analysis; Saeed Sadigh-Eteghad: literature search; Mostafa Araj-Khodaei and Mohammad Hossein Ayati: Supervision, Project administration; Sasan Andalib; Writing—Review & Editing. All the authors have read and approved the final manuscript.

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Correspondence to Mostafa Araj-Khodaei or Mohammad Hossein Ayati.

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Sanaie, S., Nikanfar, S., Kalekhane, Z.Y. et al. Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights. Metab Brain Dis 38, 137–162 (2023). https://doi.org/10.1007/s11011-022-01059-5

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