TY - JOUR
T1 - The isoflavones and extracts from Maclura tricuspidata fruit protect against neuronal cell death in ischemic injury via induction of Nox4-targeting miRNA-25, miRNA-92a, and miRNA-146a
AU - Hong, Sungeun
AU - Kwon, Jaeyoung
AU - Hiep, Nguyen Tuan
AU - Sim, Su Jin
AU - Kim, Nahyun
AU - Kim, Kyeong Ho
AU - Lee, Dongho
AU - Mar, Woongchon
N1 - Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea (Grant no. NRF-2015R1A1A01056603 and NRF-2015R1D1A1A01060321 ) and the BK21 plus program in 2016 through the National Research Foundation (NRF) funded by the Ministry of Education of Korea . The author appreciates Korea University and the Korea Forest Research Institute for supporting the plant materials.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/1
Y1 - 2018/1
N2 - This study evaluated the neuroprotective effects 50% EtOH extract of Maclura tricuspidata fruits (FME50) and isolated compounds, cudraisoflavone I (CFI), and cudraisoflavone H (CFH), on ischemic damage in in vitro model and in vivo model of cerebral ischemia. FME50, CFI, and CFH inhibited OGD/R + glucose-induced neuronal cell death, ROS generation, and Nox4 expression via induction of Nox4-targeting miRNA-25, miRNA-92a, and miRNA-146a in SH-SY5Y cells. Also, FME50 suppressed OGD/R + glucose-induced activation of ASK1-JNK1/p38 MAPK signal cascade. Furthermore, FME50 significantly reduced the MCAO/R-induced brain infarct, Nox4 expression via induction of Nox4-targeting three miRNAs. Additionally, FME50 suppressed MCAO/R-induced MAPK signal pathway. These results demonstrate that FME50, CFI, and CFH exert neuroprotective effects via Nox4 inhibition by the induction of Nox4-targeting miRNAs and inhibition of MAPK signal cascade, suggesting that they might be possible candidates for the treatment of cerebral ischemia.
AB - This study evaluated the neuroprotective effects 50% EtOH extract of Maclura tricuspidata fruits (FME50) and isolated compounds, cudraisoflavone I (CFI), and cudraisoflavone H (CFH), on ischemic damage in in vitro model and in vivo model of cerebral ischemia. FME50, CFI, and CFH inhibited OGD/R + glucose-induced neuronal cell death, ROS generation, and Nox4 expression via induction of Nox4-targeting miRNA-25, miRNA-92a, and miRNA-146a in SH-SY5Y cells. Also, FME50 suppressed OGD/R + glucose-induced activation of ASK1-JNK1/p38 MAPK signal cascade. Furthermore, FME50 significantly reduced the MCAO/R-induced brain infarct, Nox4 expression via induction of Nox4-targeting three miRNAs. Additionally, FME50 suppressed MCAO/R-induced MAPK signal pathway. These results demonstrate that FME50, CFI, and CFH exert neuroprotective effects via Nox4 inhibition by the induction of Nox4-targeting miRNAs and inhibition of MAPK signal cascade, suggesting that they might be possible candidates for the treatment of cerebral ischemia.
KW - MAPkinase
KW - Maclura tricuspidata
KW - Middle cerebral artery occlusion/reperfusion
KW - MiroRNAs
KW - NADPH oxidase
KW - Oxygen-glucose deprivation/reoxygenation + glucose
UR - http://www.scopus.com/inward/record.url?scp=85037976304&partnerID=8YFLogxK
U2 - 10.1016/j.jff.2017.12.011
DO - 10.1016/j.jff.2017.12.011
M3 - Article
AN - SCOPUS:85037976304
SN - 1756-4646
VL - 40
SP - 785
EP - 797
JO - Journal of Functional Foods
JF - Journal of Functional Foods
ER -