PMID- 31534619
OWN - NLM
STAT- MEDLINE
DCOM- 20200320
LR  - 20200320
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - Sesamin Enhances Nrf2-Mediated Protective Defense against Oxidative Stress and 
      Inflammation in Colitis via AKT and ERK Activation.
PG  - 2432416
LID - 10.1155/2019/2432416 [doi]
LID - 2432416
AB  - Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) with 
      high incidence and prevalence in many countries. Patients with UC usually suffer 
      from a lifetime of debilitating physical symptoms. Therefore, developing 
      effective therapeutic strategy that can manage this disease better and improve 
      patients' life quality is in urgent need. Sesamin (SSM) is a lignan derived from 
      sesame seeds. In this study, the protective effect of SSM against UC and the 
      underlying mechanism were investigated in vitro and in vivo. Our data showed that 
      SSM protected Caco-2 cells from H(2)O(2)-induced oxidative stress injury via 
      GSH-mediated scavenging of reactive oxygen species (ROS). Dual luciferase 
      reporter assay showed that the transcriptional activity of nuclear factor 
      erythroid-related factor 2 (Nrf2) was significantly increased by SSM, and the 
      ability of SSM to activate Nrf2-targeted genes was further confirmed in Caco-2 
      cells using western blot and quantitative real-time PCR (qRT-PCR). In contrast, 
      Nrf2 knockdown abolished the protective effect of SSM. Additionally, we found 
      that SSM also activated advanced protein kinase B (AKT) and extracellular 
      signal-regulated kinase (ERK) in Caco-2 cells, while either AKT or ERK inhibition 
      can prevent SSM-mediated nuclear translocation of Nrf2. Furthermore, SSM 
      displayed a better protective effect against dextran sulfate sodium- (DSS-) 
      induced UC compared with 5-aminosalicylic acid (5-ASA) in C57BL/6 mice. The 
      enhanced Nrf2 signaling and activated AKT/ERK were also observed in the colon of 
      mice after SSM administration. These results first demonstrate the protective 
      effect of SSM against UC and indicate that the effect is associated with AKT/ERK 
      activation and subsequent Nrf2 signaling enhancement. This study provides a new 
      insight into the medicinal value of SSM and proposes it as a new natural 
      nutrition for better managing the symptoms of UC.
FAU - Bai, Xupeng
AU  - Bai X
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
AD  - St George and Sutherland Clinical School, Faculty of Medicine, UNSW Sydney, 
      Australia.
FAU - Gou, Xiaoli
AU  - Gou X
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Cai, Peiheng
AU  - Cai P
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Xu, Chuncao
AU  - Xu C
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Cao, Lin
AU  - Cao L
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Zhao, Zhongxiang
AU  - Zhao Z
AD  - School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Huang, Min
AU  - Huang M
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Jin, Jing
AU  - Jin J
AUID- ORCID: 0000-0001-7384-0092
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20190826
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Antioxidants)
RN  - 0 (Dioxoles)
RN  - 0 (Lignans)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - S7946O4P76 (sesamin)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Caco-2 Cells
MH  - Colitis/*drug therapy/metabolism/pathology
MH  - Dioxoles/*pharmacology
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Lignans/*pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Oxidative Stress/*drug effects
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Transcriptional Activation
PMC - PMC6732632
COIS- There are no potential conflicts of interest in this study.
EDAT- 2019/09/20 06:00
MHDA- 2020/03/21 06:00
PMCR- 2019/08/26
CRDT- 2019/09/20 06:00
PHST- 2019/01/14 00:00 [received]
PHST- 2019/04/18 00:00 [revised]
PHST- 2019/07/14 00:00 [accepted]
PHST- 2019/09/20 06:00 [entrez]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/03/21 06:00 [medline]
PHST- 2019/08/26 00:00 [pmc-release]
AID - 10.1155/2019/2432416 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Aug 26;2019:2432416. doi: 10.1155/2019/2432416. 
      eCollection 2019.