PMID- 25926716
OWN - NLM
STAT- MEDLINE
DCOM- 20160209
LR  - 20181113
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 9
DP  - 2015
TI  - Schisandrin B inhibits cell growth and induces cellular apoptosis and autophagy 
      in mouse hepatocytes and macrophages: implications for its hepatotoxicity.
PG  - 2001-27
LID - 10.2147/DDDT.S77071 [doi]
AB  - A number of drugs and herbal compounds have been documented to cause 
      hepatoxicity. Schisandrin B (Sch B) is an active dibenzocyclooctadiene isolated 
      from Schisandrae fructus, with a wide array of pharmacological activities. 
      However, the potential hepatotoxicity of Sch B is a major safety concern, and the 
      underlying mechanism for Sch B-induced liver toxic effects is not fully 
      elucidated. In the present study, we aimed to investigate the liver toxic effects 
      and the molecular mechanisms of Sch B in mouse liver and macrophage cells. The 
      results have shown that Sch B exhibits potent grow inhibitory, proapoptotic, and 
      proautophagic effects in AML-12 and RAW 264.7 cells. Sch B markedly arrested 
      cells in G1 phase in both cell lines, accompanied by the down-regulation of 
      cyclin dependent kinase 2 (CDK2) and cyclin D1 and up-regulation of p27 Kip1 and 
      checkpoint kinase 1. Furthermore, Sch B markedly increased the apoptosis of 
      AML-12 and RAW 264.7 cells with a decrease in the expression of B-cell 
      lymphoma-extra-large and (Bcl-xl) B-cell lymphoma 2 (Bcl-2), but an increase in 
      the expression of B-cell lymphoma 2-associated X protein (Bax). Sch B promoted 
      the cleavage of caspase 3 and poly-adenosine diphosphate-ribose polymerase (PARP) 
      in both cell lines. Additionally, Sch B significantly induced autophagy of AML-12 
      and RAW 264.7 cells. Sch B inhibited the activation of phosphatidylinositol 
      3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) 
      signaling pathway, as indicated by their altered phosphorylation, contributing to 
      the proautophagic effect of Sch B. Taken together, our findings show that the 
      inducing effects of Sch B on cell cycle arrest, apoptosis, and autophagy may 
      contribute to its liver toxic effects, which might provide a clue for the 
      investigation of the molecular toxic targets and underlying mechanisms for Sch 
      B-induced hepatotoxicity in herbal consumers. More studies are warranted to fully 
      delineate the underlying mechanisms, efficacy, and safety of Sch B for clinical 
      use.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, People's Republic of China ; Department of 
      Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, 
      FL, USA.
FAU - Zhou, Zhi-Wei
AU  - Zhou ZW
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
FAU - Jin, Hua
AU  - Jin H
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
FAU - Hu, Chengbin
AU  - Hu C
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
FAU - He, Zhi-Xu
AU  - He ZX
AD  - Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue 
      Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, 
      Guiyang Medical University, Guiyang, Guizhou, People's Republic of China.
FAU - Yu, Zhi-Ling
AU  - Yu ZL
AD  - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People's 
      Republic of China.
FAU - Ko, Kam-Ming
AU  - Ko KM
AD  - Division of Life Science, Hong Kong University of Science and Technology, Hong 
      Kong, People's Republic of China.
FAU - Yang, Tianxin
AU  - Yang T
AD  - Department of Internal Medicine, University of Utah and Salt Lake Veterans 
      Affairs Medical Center, Salt Lake City, UT, USA.
FAU - Zhang, Xueji
AU  - Zhang X
AD  - Research Center for Bioengineering and Sensing Technology, University of Science 
      and Technology Beijing, Beijing, People's Republic of China.
FAU - Pan, Si-Yuan
AU  - Pan SY
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, People's Republic of China.
FAU - Zhou, Shu-Feng
AU  - Zhou SF
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150409
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Cyclooctanes)
RN  - 0 (Lignans)
RN  - 0 (Polycyclic Compounds)
RN  - 02XA4X3KZW (schizandrin B)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chemical and Drug Induced Liver Injury/*pathology
MH  - Cyclooctanes/pharmacology/toxicity
MH  - G1 Phase/drug effects
MH  - Hepatocytes/*drug effects
MH  - Lignans/*pharmacology/*toxicity
MH  - Macrophages/*drug effects
MH  - Mice
MH  - Mitochondria, Liver/drug effects
MH  - Polycyclic Compounds/*pharmacology/*toxicity
MH  - S Phase/drug effects
MH  - Signal Transduction/drug effects
PMC - PMC4403607
OTO - NOTNLM
OT  - AML-12 cell
OT  - Bcl-2
OT  - RAW 264.7 cell
OT  - herbal medicine
OT  - liver toxicity
OT  - mTOR
EDAT- 2015/05/01 06:00
MHDA- 2016/02/10 06:00
PMCR- 2015/04/09
CRDT- 2015/05/01 06:00
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2016/02/10 06:00 [medline]
PHST- 2015/04/09 00:00 [pmc-release]
AID - dddt-9-2001 [pii]
AID - 10.2147/DDDT.S77071 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2015 Apr 9;9:2001-27. doi: 10.2147/DDDT.S77071. eCollection 
      2015.