PMID- 28464236
OWN - NLM
STAT- MEDLINE
DCOM- 20180316
LR  - 20200930
IS  - 2042-7158 (Electronic)
IS  - 0022-3573 (Linking)
VI  - 69
IP  - 7
DP  - 2017 Jul
TI  - Neuroprotection by plumbagin involves BDNF-TrkB-PI3K/Akt and ERK1/2/JNK pathways 
      in isoflurane-induced neonatal rats.
PG  - 896-906
LID - 10.1111/jphp.12681 [doi]
AB  - OBJECTIVES: This study was designed to assess the effects of plumbagin on 
      isoflurane-induced neurotoxicity. METHODS: Neonatal Sprague Dawley rat pups were 
      treated with plumbagin (50, 100 or 150 mg/kg body weight, orally) from postnatal 
      day 2. The pups on postnatal day 7 were subjected to isoflurane (0.75%) exposure 
      for 6 h. Neuronal apoptosis in the hippocampal tissues was detected by TUNEL 
      assay and FluroJade B staining following isoflurane exposure. Protein expressions 
      were analysed by immunoblotting. RT-PCR was performed to assess mRNA levels of 
      brain-derived neurotrophic factor (BDNF) and TrkB. KEY FINDINGS: We observed 
      reduced apoptosis in hippocampal CA1, CA3 and dentate gyrus regions along with 
      severely reduced pro-apoptotic factors (Bad, Bax and cleaved caspase-3) 
      expression and raised levels of Bcl-2, Bcl-xL, survivin, xIAP and cIAPs (cell 
      survival proteins) in plumbagin supplemented rats. Decrease in the levels of JNK, 
      phospho-JNK, c-Jun and phospho-c-Jun with enhanced ERK1/2 levels was observed on 
      plumbagin pretreatment. Down-regulated PI3K/Akt signalling following isoflurane 
      was activated by plumbagin as evidenced by raised PI3K/Akt pathway proteins - 
      mTORc1, Akt, phospho-Akt, GSK-3beta, phospho-GSK-3beta, PTEN and NF-kappaBp65 in the 
      hippocampal tissues as detected by Western blotting. The mRNA levels were 
      enhanced on plumbagin supplementation. CONCLUSIONS: Plumbagin exerted its 
      neuroprotective effects by effectively suppressing isoflurane-induced neuronal 
      apoptosis via regulating BDNF-TrkB-PI3/Akt and ERK/JNK signalling.
CI  - (c) 2017 Royal Pharmaceutical Society.
FAU - Yuan, Jun-Hui
AU  - Yuan JH
AD  - Department of Neonatology, Wenling Maternal and Child Health Hospital, Wenling, 
      Zhejiang, China.
FAU - Pan, Feng
AU  - Pan F
AD  - Department of Neonatology, Wenling Maternal and Child Health Hospital, Wenling, 
      Zhejiang, China.
FAU - Chen, Jie
AU  - Chen J
AD  - Taizhou University Medical School, Taizhou, Zhejiang, China.
FAU - Chen, Cai-Er
AU  - Chen CE
AD  - Department of Neonatology, Wenling Maternal and Child Health Hospital, Wenling, 
      Zhejiang, China.
FAU - Xie, Deng-Pan
AU  - Xie DP
AD  - Department of Neonatology, Wenling Maternal and Child Health Hospital, Wenling, 
      Zhejiang, China.
FAU - Jiang, Xing-Zhu
AU  - Jiang XZ
AD  - Department of Neonatology, Wenling Maternal and Child Health Hospital, Wenling, 
      Zhejiang, China.
FAU - Guo, Su-Juan
AU  - Guo SJ
AD  - Department of Neonatology, Wenling Maternal and Child Health Hospital, Wenling, 
      Zhejiang, China.
FAU - Zhou, Jun
AU  - Zhou J
AD  - Taizhou University Medical School, Taizhou, Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20170502
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Naphthoquinones)
RN  - 0 (Neuroprotective Agents)
RN  - CYS9AKD70P (Isoflurane)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - YAS4TBQ4OQ (plumbagin)
SB  - IM
MH  - Anesthetics, Inhalation/toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Hippocampus/drug effects/pathology
MH  - In Situ Nick-End Labeling
MH  - Isoflurane/toxicity
MH  - MAP Kinase Signaling System/drug effects
MH  - Naphthoquinones/*pharmacology
MH  - Neuroprotective Agents/*pharmacology
MH  - Neurotoxicity Syndromes/*prevention & control
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - PI3K/Akt signalling cascade
OT  - brain-derived neurotrophic factor
OT  - isoflurane
OT  - mitogen-activated protein kinases
OT  - plumbagin
EDAT- 2017/05/04 06:00
MHDA- 2018/03/17 06:00
CRDT- 2017/05/03 06:00
PHST- 2016/06/13 00:00 [received]
PHST- 2016/11/12 00:00 [accepted]
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2018/03/17 06:00 [medline]
PHST- 2017/05/03 06:00 [entrez]
AID - 10.1111/jphp.12681 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2017 Jul;69(7):896-906. doi: 10.1111/jphp.12681. Epub 2017 May 
      2.