PMID- 26806302
OWN - NLM
STAT- MEDLINE
DCOM- 20170110
LR  - 20220330
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 37
IP  - 3
DP  - 2016 Mar
TI  - Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice 
      via activation of the NRF2/ARE signaling pathway.
PG  - 382-9
LID - 10.1038/aps.2015.120 [doi]
AB  - AIM: The nuclear factor erythroid 2-related factor 2 (NRF2) acts through the 
      antioxidant response element (ARE) to regulate the expression of many detoxifying 
      and antioxidant genes responsible for cytoprotective processes. We previously 
      reported that Schisandrol B (SolB) isolated from Schisandra sphenanthera produced 
      a protective effect against acetaminophen (APAP)-induced liver injury. In this 
      study we investigated whether the NRF2/ARE signaling pathway was involved in this 
      hepato-protective effect. METHODS: Male C57BL/6 mice were treated with SolB (200 
      mg . kg(-1) . d(-1), ig) for 3 d before injection of APAP (400 mg/kg, ip). Serum 
      and liver tissue samples were collected 6 h later. The mRNA and protein 
      expression were measured using qRT-PCR and Western blot assay, respectively. The 
      activation of NRF2 was examined in HepG2 cells using luciferase reporter gene 
      assay. RESULTS: SolB pretreatment significantly alleviated the hepatic injury 
      (large patchy necrosis and hyperemia of the hepatic sinus), the increase of serum 
      AST, ALT levels and hepatic MDA contents, and the decrease of liver and 
      mitochondrial glutathione levels in APAP-treated mice. Furthermore, SolB 
      pretreatment significantly increased nuclear accumulation of NRF2 and increased 
      hepatic expression of NRF2 downstream proteins, including GCLC, GSR, NQO1, GSTs, 
      MRP2, MRP3 and MRP4 in APAP-treated mice. Moreover, treatment with SolB (2.5-20 
      mumol/L) dose-dependently increased the activity of NRF2 reporter gene in HepG2 
      cells. CONCLUSION: SolB exhibits a remarkable protective effect against 
      APAP-induced hepatotoxicity, partially via activation of the NRF2/ARE pathway and 
      regulation of NRF2 target genes, which induce detoxification and increase 
      antioxidant capacity.
FAU - Jiang, Yi-ming
AU  - Jiang YM
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
FAU - Wang, Ying
AU  - Wang Y
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
AD  - Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510006, China.
FAU - Tan, Hua-sen
AU  - Tan HS
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
FAU - Yu, Tao
AU  - Yu T
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
FAU - Fan, Xiao-mei
AU  - Fan XM
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
FAU - Chen, Pan
AU  - Chen P
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
AD  - The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510006, China.
FAU - Zeng, Hang
AU  - Zeng H
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
FAU - Huang, Min
AU  - Huang M
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
FAU - Bi, Hui-chang
AU  - Bi HC
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160125
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Cyclooctanes)
RN  - 0 (Dioxoles)
RN  - 0 (Lignans)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Protective Agents)
RN  - 0 (RNA, Messenger)
RN  - 362O9ITL9D (Acetaminophen)
RN  - 58546-54-6 (schizandrol B)
SB  - IM
MH  - Acetaminophen/*toxicity
MH  - Analgesics, Non-Narcotic/*toxicity
MH  - Animals
MH  - Antioxidant Response Elements/*drug effects
MH  - Chemical and Drug Induced Liver Injury/metabolism/pathology/*prevention & control
MH  - Cyclooctanes/isolation & purification/*therapeutic use
MH  - Dioxoles/isolation & purification/*therapeutic use
MH  - Gene Expression Regulation/drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - Lignans/isolation & purification/*therapeutic use
MH  - Liver/*drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Protective Agents/isolation & purification/*therapeutic use
MH  - RNA, Messenger/genetics
MH  - Schisandra/chemistry
MH  - Signal Transduction/drug effects
PMC - PMC4775844
EDAT- 2016/01/26 06:00
MHDA- 2017/01/11 06:00
PMCR- 2016/03/01
CRDT- 2016/01/26 06:00
PHST- 2014/12/10 00:00 [received]
PHST- 2015/08/25 00:00 [accepted]
PHST- 2016/01/26 06:00 [entrez]
PHST- 2016/01/26 06:00 [pubmed]
PHST- 2017/01/11 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - aps2015120 [pii]
AID - 10.1038/aps.2015.120 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2016 Mar;37(3):382-9. doi: 10.1038/aps.2015.120. Epub 2016 
      Jan 25.