Orobol derivatives and extracts from Cudrania tricuspidata fruits protect against 6-hydroxydomamine-induced neuronal cell death by enhancing proteasome activity and the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1

Dong Woo Kim, Jaeyoung Kwon, Su Jin Sim, Dongho Lee, Woongchon Mar

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5 Citations (Scopus)

Abstract

We investigated the neuroprotective effects of orobol derivatives and ethanol extracts from Cudrania tricuspidata fruits. Among the nine isolates from a 50% ethanol extract from Cudrania tricuspidata fruits (CTE50), orobol (OB), 6-prenylorobol (POB), and 6,8-diprenylorobol (DPOB) showed neuroprotective effects in 6-OHDA-induced SH-SY5Y cell death. In addition, CTE50 and the three orobol derivatives (OB, POB, and DPOB) attenuated the cleavage of caspase-3, caspase-9, and PARP and inhibited the excessive generation of ROS. Furthermore, it enhanced the 6-OHDA-induced dysfunction of proteasome activity and reduced the accumulation of ubiquitin conjugated-proteins and the polyubiquitination of α-synuclein and synphilin-1. The proteasome inhibitor MG132 blocked the neuroprotective effects and the enhanced proteasome activity produced by CTE50 and the three orobol derivatives. These results demonstrate that CTE50 and three orobol derivatives protect against 6-OHDA-induced neurotoxicity by enhancing the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1, suggesting that they might be possible candidates for the treatment of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)104-114
Number of pages11
JournalJournal of Functional Foods
Volume29
DOIs
Publication statusPublished - 2017 Feb 1

Fingerprint

Maclura tricuspidata
Synucleins
Moraceae
proteasome endopeptidase complex
Proteasome Endopeptidase Complex
ubiquitin
Ubiquitin
neuroprotective effect
cell death
Fruit
Cell Death
chemical derivatives
neurons
fruits
degradation
Oxidopamine
extracts
Neuroprotective Agents
conjugated proteins
ethanol

Keywords

  • 6-OHDA
  • Cudrania tricuspidata
  • Neuroprotection
  • Orobol derivatives
  • Polyubiquitination
  • Proteasome activity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science
  • Nutrition and Dietetics

Cite this

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title = "Orobol derivatives and extracts from Cudrania tricuspidata fruits protect against 6-hydroxydomamine-induced neuronal cell death by enhancing proteasome activity and the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1",
abstract = "We investigated the neuroprotective effects of orobol derivatives and ethanol extracts from Cudrania tricuspidata fruits. Among the nine isolates from a 50{\%} ethanol extract from Cudrania tricuspidata fruits (CTE50), orobol (OB), 6-prenylorobol (POB), and 6,8-diprenylorobol (DPOB) showed neuroprotective effects in 6-OHDA-induced SH-SY5Y cell death. In addition, CTE50 and the three orobol derivatives (OB, POB, and DPOB) attenuated the cleavage of caspase-3, caspase-9, and PARP and inhibited the excessive generation of ROS. Furthermore, it enhanced the 6-OHDA-induced dysfunction of proteasome activity and reduced the accumulation of ubiquitin conjugated-proteins and the polyubiquitination of α-synuclein and synphilin-1. The proteasome inhibitor MG132 blocked the neuroprotective effects and the enhanced proteasome activity produced by CTE50 and the three orobol derivatives. These results demonstrate that CTE50 and three orobol derivatives protect against 6-OHDA-induced neurotoxicity by enhancing the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1, suggesting that they might be possible candidates for the treatment of neurodegenerative diseases.",
keywords = "6-OHDA, Cudrania tricuspidata, Neuroprotection, Orobol derivatives, Polyubiquitination, Proteasome activity",
author = "Kim, {Dong Woo} and Jaeyoung Kwon and Sim, {Su Jin} and Dongho Lee and Woongchon Mar",
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TY - JOUR

T1 - Orobol derivatives and extracts from Cudrania tricuspidata fruits protect against 6-hydroxydomamine-induced neuronal cell death by enhancing proteasome activity and the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1

AU - Kim, Dong Woo

AU - Kwon, Jaeyoung

AU - Sim, Su Jin

AU - Lee, Dongho

AU - Mar, Woongchon

PY - 2017/2/1

Y1 - 2017/2/1

N2 - We investigated the neuroprotective effects of orobol derivatives and ethanol extracts from Cudrania tricuspidata fruits. Among the nine isolates from a 50% ethanol extract from Cudrania tricuspidata fruits (CTE50), orobol (OB), 6-prenylorobol (POB), and 6,8-diprenylorobol (DPOB) showed neuroprotective effects in 6-OHDA-induced SH-SY5Y cell death. In addition, CTE50 and the three orobol derivatives (OB, POB, and DPOB) attenuated the cleavage of caspase-3, caspase-9, and PARP and inhibited the excessive generation of ROS. Furthermore, it enhanced the 6-OHDA-induced dysfunction of proteasome activity and reduced the accumulation of ubiquitin conjugated-proteins and the polyubiquitination of α-synuclein and synphilin-1. The proteasome inhibitor MG132 blocked the neuroprotective effects and the enhanced proteasome activity produced by CTE50 and the three orobol derivatives. These results demonstrate that CTE50 and three orobol derivatives protect against 6-OHDA-induced neurotoxicity by enhancing the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1, suggesting that they might be possible candidates for the treatment of neurodegenerative diseases.

AB - We investigated the neuroprotective effects of orobol derivatives and ethanol extracts from Cudrania tricuspidata fruits. Among the nine isolates from a 50% ethanol extract from Cudrania tricuspidata fruits (CTE50), orobol (OB), 6-prenylorobol (POB), and 6,8-diprenylorobol (DPOB) showed neuroprotective effects in 6-OHDA-induced SH-SY5Y cell death. In addition, CTE50 and the three orobol derivatives (OB, POB, and DPOB) attenuated the cleavage of caspase-3, caspase-9, and PARP and inhibited the excessive generation of ROS. Furthermore, it enhanced the 6-OHDA-induced dysfunction of proteasome activity and reduced the accumulation of ubiquitin conjugated-proteins and the polyubiquitination of α-synuclein and synphilin-1. The proteasome inhibitor MG132 blocked the neuroprotective effects and the enhanced proteasome activity produced by CTE50 and the three orobol derivatives. These results demonstrate that CTE50 and three orobol derivatives protect against 6-OHDA-induced neurotoxicity by enhancing the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1, suggesting that they might be possible candidates for the treatment of neurodegenerative diseases.

KW - 6-OHDA

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KW - Orobol derivatives

KW - Polyubiquitination

KW - Proteasome activity

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