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Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress

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Pharmacological Properties of Plant-Derived Natural Products and Implications for Human Health

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1308))

Abstract

Programmed cell death processes such as apoptosis and autophagy strongly contribute to the onset and progression of cancer. Along with these lines, modulation of cell death mechanisms to combat cancer cells and elimination of resistance to apoptosis is of great interest. It appears that modulation of autophagy and endoplasmic reticulum (ER) stress with specific agents would be beneficial in the treatment of several disorders. Interestingly, it has been suggested that herbal natural products may be suitable candidates for the modulation of these processes due to few side effects and significant therapeutic potential. Ginsenosides are derivatives of ginseng and exert modulatory effects on the molecular mechanisms associated with autophagy and ER stress. Ginsenosides act as smart phytochemicals that confer their effects by up-regulating ATG proteins and converting LC3-I to -II, which results in maturation of autophagosomes. Not only do ginsenosides promote autophagy but they also possess protective and therapeutic properties due to their capacity to modulate ER stress and up- and down-regulate and/or dephosphorylate UPR transducers such as IRE1, PERK, and ATF6. Thus, it would appear that ginsenosides are promising agents to potentially restore tissue malfunction and possibly eliminate cancer.

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Abbreviations

AD:

Alzheimer’s disease

AMPK:

AMP-activated protein kinase

AS:

atherosclerosis

ASK1:

apoptosis signal-regulating kinase-1

ATF-6:

activating transcription factor-6

ATG:

autophagy-related gene

Aβ:

amyloid-β

BAX:

Bcl2-associated x protein

Beclin1:

Bcl2-interacting protein 1

CHOP:

C/EBP homologous protein

CMA:

chaperone-mediated autophagy

DAPK1:

death-associated protein kinase 1

DDIT3:

DNA damage-inducible transcript 3

DM:

diabetes mellitus

DR5:

death receptor 5

elF2α:

eukaryotic translocation factor 2α

ER:

endoplasmic reticulum

ERAD:

ER-associated degradation

ERK:

extracellular signal-regulated kinase

FDA:

Food and Drug Administration

GFB:

glomerular filtration barrier

GSK-3β:

glycogen synthase kinase-3β

I/R:

ischemic/reperfusion

IL:

interleukin

IRE1:

inositol-requiring enzyme-1

JNK:

c-Jun N-terminal kinase

LC3:

light chain-3

LPS:

lipopolysaccharide

miR:

microRNA

mTOR:

mechanistic target of rapamycin

NAFLD:

non-alcoholic fatty liver disease

NDs:

neurological disorders

NLRP3:

nucleotide-binding domain and leucine-rich repeat containing protein 3

Nrf2:

nuclear factor erythroid 2-related factor 2

PD:

Parkinson’s disease

PERK:

PRK-like ER kinase

PI3K:

phosphoinositide 3-kinase

SCI:

spinal cord injury

SGLT1:

sodium-dependent glucose co-transporter 1

SHP:

small heterodimer protein

Sirt1:

sirtuin1

t-BHP:

tert-Butyl hydroperoxide

TRAF2:

tumor necrosis factor receptor-associated factor 2

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

ULK1/2:

unc51-like autophagy activating kinase 1/2

UPR:

unfolded protein response

XBP1:

X box-binding protein 1

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Authors declare that they do not have conflict of interests.

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Authors and Affiliations

  1. Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey

    Milad Ashrafizadeh

  2. Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul, Turkey

    Milad Ashrafizadeh

  3. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Shima Tavakol

  4. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Reza Mohammadinejad

  5. Department of Basic Sciences, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran

    Zahra Ahmadi

  6. Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran

    Habib Yaribeygi

  7. Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran

    Tannaz Jamialahmadi

  8. Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Tannaz Jamialahmadi

  9. Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA

    Thomas P. Johnston

  10. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  11. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  12. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  13. Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland

    Amirhossein Sahebkar

Authors
  1. Milad Ashrafizadeh
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  2. Shima Tavakol
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  3. Reza Mohammadinejad
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  4. Zahra Ahmadi
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  5. Habib Yaribeygi
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  6. Tannaz Jamialahmadi
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  7. Thomas P. Johnston
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  8. Amirhossein Sahebkar
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Corresponding authors

Correspondence to Habib Yaribeygi or Amirhossein Sahebkar .

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Editors and Affiliations

  1. Department of Biological Sciences, University of Limerick, Limerick, Ireland

    George E. Barreto

  2. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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Ashrafizadeh, M. et al. (2021). Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress. In: Barreto, G.E., Sahebkar, A. (eds) Pharmacological Properties of Plant-Derived Natural Products and Implications for Human Health. Advances in Experimental Medicine and Biology, vol 1308. Springer, Cham. https://doi.org/10.1007/978-3-030-64872-5_12

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