Schisandrin B shows neuroprotective effect in 6-OHDA-induced Parkinson's disease via inhibiting the negative modulation of miR-34a on Nrf2 pathway.
BACKGROUND
MiR-34 family members have been previously shown to play potential functional role in Parkinson's disease (PD) pathogenesis. However, the regulatory role of miR-34a has not been demonstrated in PD yet. This study aims to clarify the potential neuroprotective effect of Schisandrin B (Sch B) involving miR-34a function in 6-OHDA-induced PD model.


METHODS
The expression changes of miR-34a and Nrf2 pathway related genes were detected in 6-OHDA-treated SH-SY5Y cells under Sch B pretreatment. Cell viability and PD feathers of 6-OHDA-induced PD mice were measured for neuroprotection assessment. The regulation of miR-34a on Nrf2 activity and expression was demonstrated through gain-of-function and loss-of-function studies, while the regulatory role of miR-34a in the neuroprotection of Sch B was investigated both in vitro and in vivo.


RESULTS
Sch B pretreatment ameliorated 6-OHDA-induced changes in vitro, like upregulated miR-34a expression, inhibited Nrf2 pathways and decreased cell survival, and PD feathers in vivo. Moreover, Nrf2 was negatively regulated by miR-34a, while miR-34a overexpression inhibited the neuroprotection of Sch B in both dopaminergic SH-SY5Y cells and PD mice.


CONCLUSIONS
Sch B showed neuroprotective effect in 6-OHDA-induced PD pathogenesis, which could be inhibited by miR-34a, involving the negative regulatory mechanism of miR-34a on Nrf2 pathways.
Department of Neurology, People's Hospital of Zhengzhou, Zhengzhou, China. Electronic address: baqingh@163.com.
Qinghua
Q
Ba
Department of Neurology, the First People's Hospital of Zhengzhou, Zhengzhou, China.
Chuanju
C
Cui
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Lijun
L
Wen
Department of Neurology, People's Hospital of Zhengzhou, Zhengzhou, China.
Shutao
S
Feng
Department of Neurology, People's Hospital of Zhengzhou, Zhengzhou, China.
Junchao
J
Zhou
Department of Neurology, People's Hospital of Zhengzhou, Zhengzhou, China.
Ke
K
Yang
D020413:3' Untranslated Regions; D000818:Animals; D001522:Behavior, Animal; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D034242:Cyclooctanes / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D020413:3' Untranslated Regions; D034242:Cyclooctanes; D017705:Lignans; C522425:MIRN34 microRNA, human; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D011083:Polycyclic Compounds; C015499:schizandrin B; D016627:Oxidopamine
6-OHDA; MiR-34a; Nrf2; Parkinson’s disease; Schisandrin B