PMID- 36400161
OWN - NLM
STAT- MEDLINE
DCOM- 20230117
LR  - 20230117
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 940
DP  - 2023 Feb 5
TI  - Ginsenoside Rh2 inhibits CBP/p300-mediated FOXO3a acetylation and 
      epilepsy-induced oxidative damage via the FOXO3a-KEAP1-NRF2 pathway.
PG  - 175391
LID - S0014-2999(22)00652-5 [pii]
LID - 10.1016/j.ejphar.2022.175391 [doi]
AB  - Epilepsy is a chronic disease that affects a wide range of people. Furthermore, a 
      third of patients suffering from epileptic seizures do not respond to 
      antiepileptic drugs. In recent years, increasing attention has focused on the 
      role of oxidative stress in acquired epilepsy, and adjuvant antiepileptic drugs 
      to reduce oxidative stress may be a new therapeutic strategy. In this study 
      ginsenoside Rh2 was resistant to oxidative stress induced by epileptic activity 
      in vivo and in vitro. Using online databases, we identified forkhead box O3a 
      (FOXO3a) overexpression in epilepsy tissue and validated this in vitro, in vivo, 
      and in clinical tissues of patients with epilepsy. An in vitro epilepsy model 
      revealed that the overexpression of FOXO3a led to more severe oxidative stress, 
      while the knockdown of FOXO3a had a protective effect on SH-SY5Y cells. Moreover, 
      our results showed that the positive effect of FOXO3a on oxidative stress was 
      caused by the transcriptional activation of Kelch-like ECH-associated protein 1 
      (KEAP1), a negative regulator of nuclear factor erythroid 2-related factor 2 
      (NRF2). We also found that ginsenoside Rh2 can directly inhibit the activation of 
      FOXO3a by selectively blocking CREB-binding protein (CBP)/p300-mediated FOXO3a 
      acetylation and play a role in regulating the KEAP1-NRF2 pathway to resist 
      oxidative stress.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Wu, Jingheng
AU  - Wu J
AD  - Department of Neurosurgery, Shengjing Hospital of China Medical University, 
      Shenyang, China; Liaoning Clinical Medical Research Center in Nervous System 
      Disease, Shenyang, China; Key Laboratory of Neuro-oncology in Liaoning Province, 
      Shenyang, China.
FAU - Wang, Shuai
AU  - Wang S
AD  - Department of Neurosurgery, Shengjing Hospital of China Medical University, 
      Shenyang, China; Liaoning Clinical Medical Research Center in Nervous System 
      Disease, Shenyang, China; Key Laboratory of Neuro-oncology in Liaoning Province, 
      Shenyang, China.
FAU - Zhao, Wujun
AU  - Zhao W
AD  - Department of Neurosurgery, Shengjing Hospital of China Medical University, 
      Shenyang, China; Liaoning Clinical Medical Research Center in Nervous System 
      Disease, Shenyang, China; Key Laboratory of Neuro-oncology in Liaoning Province, 
      Shenyang, China.
FAU - Li, Miaomiao
AU  - Li M
AD  - Department of Neurosurgery, Shengjing Hospital of China Medical University, 
      Shenyang, China; Liaoning Clinical Medical Research Center in Nervous System 
      Disease, Shenyang, China; Key Laboratory of Neuro-oncology in Liaoning Province, 
      Shenyang, China.
FAU - Li, Shaoyi
AU  - Li S
AD  - Department of Neurosurgery, Shengjing Hospital of China Medical University, 
      Shenyang, China; Liaoning Clinical Medical Research Center in Nervous System 
      Disease, Shenyang, China; Key Laboratory of Neuro-oncology in Liaoning Province, 
      Shenyang, China. Electronic address: lishaoyi2097@163.com.
LA  - eng
PT  - Journal Article
DEP - 20221115
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 78214-33-2 (ginsenoside Rh2)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - 0 (Anticonvulsants)
RN  - 0 (KEAP1 protein, human)
SB  - IM
MH  - Humans
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - CREB-Binding Protein/metabolism/pharmacology
MH  - Acetylation
MH  - Anticonvulsants/pharmacology
MH  - *Neuroblastoma
MH  - Oxidative Stress
MH  - *Epilepsy/drug therapy
OTO - NOTNLM
OT  - Epilepsy
OT  - FOXO3a acetylation
OT  - Ginsenoside Rh2
OT  - KEAP1-NRF2 pathway
OT  - Oxidative stress
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/19 06:00
MHDA- 2023/01/18 06:00
CRDT- 2022/11/18 19:24
PHST- 2022/07/22 00:00 [received]
PHST- 2022/11/01 00:00 [revised]
PHST- 2022/11/10 00:00 [accepted]
PHST- 2022/11/19 06:00 [pubmed]
PHST- 2023/01/18 06:00 [medline]
PHST- 2022/11/18 19:24 [entrez]
AID - S0014-2999(22)00652-5 [pii]
AID - 10.1016/j.ejphar.2022.175391 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2023 Feb 5;940:175391. doi: 10.1016/j.ejphar.2022.175391. Epub 
      2022 Nov 15.