Chemical and biological evaluation of nephrocizin in protecting nerve growth factor-differentiated PC12 cells by 6-hydroxydopamine-induced neurotoxicity

Yi Pei Lin, Tai Yuan Chen, Hsiang Wen Tseng, Mei Hsien Lee, Shui Tein Chen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely used to generate an experimental model of Parkinson's disease. This model is crucial in the search for compounds that diminish 6-OHDA-induced nerve growth factor (NGF)-differentiated PC12 cell death. Nephrocizin (luteolin-7-O-β-d- glucopyranoside), a flavone glycoside, was isolated from widely distributed plants. The protective effects of pre-treatment with nephrocizin on the induced neurotoxicity in PC12 cells by 6-OHDA and its oxidative products, H 2O2 and p-quinone, were evaluated herein. Nephrocizin promoted cell viability, scavenged ROS-related products, increased cellular glutathione (GSH) levels, and reduced caspase-3 and -8 activities in 6-OHDA-, H2O2-, or p-quinone-treated PC12 cells. Furthermore, nephrocizin-conjugated metabolites in PC12 cells were identified with the boronate-affinity method and LC-MS technology, and preferential regioselectivity at the C2′ and C5′ positions by the nephrocizin-GSH (or NAC) adduct method was observed. These lines of evidence established that nephrocizin could form a dimer to diminish the intracellular ROS. These results demonstrate the first neuroprotective mechanism of nephrocizin against 6-OHDA-, H 2O2- or p-quinone-induced cytotoxicity in PC12 cells via chemical and biological studies. These dietary antioxidants are potential candidates for use in intervention in neurodegenerative diseases.

Original languageEnglish
Pages (from-to)102-115
Number of pages14
JournalPhytochemistry
Volume84
DOIs
Publication statusPublished - Dec 2012

Fingerprint

nerve growth factor
neurotoxicity
Oxidopamine
PC12 Cells
Nerve Growth Factor
quinones
cells
flavone
neurotoxins
Parkinson disease
luteolin
neurodegenerative diseases
caspase-3
flavones
cell viability
protective effect
glycosides
cytotoxicity
cell death
glutathione

Keywords

  • 6-Hydroxydopamine
  • Arecaceae
  • Chemical and biological studies
  • Formosa date palm
  • HO
  • Nephrocizin
  • Neuroprotection
  • p-Quinone
  • Phoenix hanceana Naudin var. formosana

ASJC Scopus subject areas

  • Plant Science
  • Biochemistry
  • Molecular Biology
  • Horticulture

Cite this

Chemical and biological evaluation of nephrocizin in protecting nerve growth factor-differentiated PC12 cells by 6-hydroxydopamine-induced neurotoxicity. / Lin, Yi Pei; Chen, Tai Yuan; Tseng, Hsiang Wen; Lee, Mei Hsien; Chen, Shui Tein.

In: Phytochemistry, Vol. 84, 12.2012, p. 102-115.

Research output: Contribution to journalArticle

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abstract = "The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely used to generate an experimental model of Parkinson's disease. This model is crucial in the search for compounds that diminish 6-OHDA-induced nerve growth factor (NGF)-differentiated PC12 cell death. Nephrocizin (luteolin-7-O-β-d- glucopyranoside), a flavone glycoside, was isolated from widely distributed plants. The protective effects of pre-treatment with nephrocizin on the induced neurotoxicity in PC12 cells by 6-OHDA and its oxidative products, H 2O2 and p-quinone, were evaluated herein. Nephrocizin promoted cell viability, scavenged ROS-related products, increased cellular glutathione (GSH) levels, and reduced caspase-3 and -8 activities in 6-OHDA-, H2O2-, or p-quinone-treated PC12 cells. Furthermore, nephrocizin-conjugated metabolites in PC12 cells were identified with the boronate-affinity method and LC-MS technology, and preferential regioselectivity at the C2′ and C5′ positions by the nephrocizin-GSH (or NAC) adduct method was observed. These lines of evidence established that nephrocizin could form a dimer to diminish the intracellular ROS. These results demonstrate the first neuroprotective mechanism of nephrocizin against 6-OHDA-, H 2O2- or p-quinone-induced cytotoxicity in PC12 cells via chemical and biological studies. These dietary antioxidants are potential candidates for use in intervention in neurodegenerative diseases.",
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