PMID- 36463449
OWN - NLM
STAT- MEDLINE
DCOM- 20230801
LR  - 20230904
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 94
IP  - s1
DP  - 2023
TI  - Neuroprotective Effect of Phloretin in Rotenone-Induced Mice Model of Parkinson's 
      Disease: Modulating mTOR-NRF2-p62 Mediated Autophagy-Oxidative Stress Crosstalk.
PG  - S109-S124
LID - 10.3233/JAD-220793 [doi]
AB  - BACKGROUND: Parkinson's disease (PD) is an age-related progressive 
      multifactorial, neurodegenerative disease. The autophagy and Keap1-Nrf2 axis 
      system are both implicated in the oxidative-stress response, metabolic stress, 
      and innate immunity, and their dysregulation is associated with pathogenic 
      processes in PD. Phloretin (PLT) is a phenolic compound reported possessing 
      anti-inflammatory and antioxidant activities. OBJECTIVE: To evaluate the 
      neuroprotective potential of PLT in PD via modulating the autophagy-antioxidant 
      axisMethods:The neuroprotective effect of PLT was evaluated in vitro using 
      rotenone (ROT) exposed SH-SY5Y cell line and in vivo using ROT administered 
      C57BL/6 mice. Mice were administered with PLT (50 and 100 mg/kg, p.o.) 
      concomitantly with ROT (1 mg/kg, i.p) for 3 weeks. Locomotive activity and 
      anxiety behaviors were assessed using rotarod and open field tests respectively. 
      Further apoptosis (Cytochrome-C, Bax), alpha-Synuclein (alpha-SYN), tyrosine hydroxylase 
      (TH), antioxidant proteins (nuclear factor erythroid 2-related factor 2 (NRF2), 
      heme oxygenase-1 (HO-1) and autophagic (mTOR, Atg5,7, p62, Beclin,LC3B-I/II) 
      protein activity were evaluated both in in vitro and in vivo. RESULTS: PLT 
      improved locomotive activity and anxiety-like behavior in mice. Further PLT 
      diminished apoptotic cell death, alpha-SYN expression and improved the expression of 
      TH, antioxidant, and autophagic regulating protein. CONCLUSION: Taken together, 
      present data deciphers that the PLT effectively improves motor and non-motor 
      symptoms via modulating the mTOR/NRF2/p62 pathway-mediated feedback loop. Hence, 
      PLT could emerge as a prospective disease-modifying drug for PD management.
FAU - Shirgadwar, Shubhendu M
AU  - Shirgadwar SM
AD  - Molecular and Cellular Neuroscience Lab, Department of Pharmacology and 
      Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), 
      Hyderabad, Telangana, India.
FAU - Kumar, Rahul
AU  - Kumar R
AD  - Molecular and Cellular Neuroscience Lab, Department of Pharmacology and 
      Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), 
      Hyderabad, Telangana, India.
FAU - Preeti, Kumari
AU  - Preeti K
AD  - Molecular and Cellular Neuroscience Lab, Department of Pharmacology and 
      Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), 
      Hyderabad, Telangana, India.
FAU - Khatri, Dharmendra Kumar
AU  - Khatri DK
AD  - Molecular and Cellular Neuroscience Lab, Department of Pharmacology and 
      Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), 
      Hyderabad, Telangana, India.
FAU - Singh, Shashi Bala
AU  - Singh SB
AD  - Molecular and Cellular Neuroscience Lab, Department of Pharmacology and 
      Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), 
      Hyderabad, Telangana, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Neuroprotective Agents)
RN  - 03L9OT429T (Rotenone)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Antioxidants)
RN  - S5J5OE47MK (Phloretin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Neuroprotective Agents/pharmacology/therapeutic use
MH  - *Parkinson Disease/drug therapy/etiology/metabolism
MH  - Rotenone/toxicity
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Antioxidants/pharmacology
MH  - *Neurodegenerative Diseases
MH  - Phloretin/pharmacology
MH  - Prospective Studies
MH  - *Neuroblastoma
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Autophagy
PMC - PMC10473071
OTO - NOTNLM
OT  - Apoptosis
OT  - Parkinson's disease
OT  - autophagy
OT  - oxidative stress
OT  - phloretin
COIS- Authors' disclosures available online 
      (https://www.j-alz.com/manuscript-disclosures/22-0793r2).
EDAT- 2022/12/05 06:00
MHDA- 2023/08/01 06:44
PMCR- 2023/09/01
CRDT- 2022/12/04 06:52
PHST- 2023/08/01 06:44 [medline]
PHST- 2022/12/05 06:00 [pubmed]
PHST- 2022/12/04 06:52 [entrez]
PHST- 2023/09/01 00:00 [pmc-release]
AID - JAD220793 [pii]
AID - 10.3233/JAD-220793 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2023;94(s1):S109-S124. doi: 10.3233/JAD-220793.