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Mild Mitochondrial Depolarization is Involved in a Neuroprotective Mechanism of Citrus sunki Peel Extract
Author(s) -
Wu JinJi,
Cui Yanji,
Yang YoonSil,
Jung SungCherl,
Hyun Jin Won,
Maeng YoungHee,
Park DeokBae,
Lee SunRyung,
Kim SeJae,
Eun SuYong
Publication year - 2013
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.4745
Subject(s) - depolarization , neuroprotection , mitochondrion , apoptosis , poly adp ribose polymerase , microbiology and biotechnology , chemistry , calcium , nobiletin , biology , pharmacology , biochemistry , biophysics , polymerase , flavonoid , antioxidant , dna , organic chemistry
Mitochondrial membrane potential (∆Ψ m ) contributes to determining a driving force for calcium to enter the mitochondria. It has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis. Therefore, mild mitochondrial depolarization has been recently evaluated as a novel mechanism of neuroprotection via inhibiting neurotoxic mitochondrial calcium overload during neuronal insults. In the present study, using both real‐time recording and flow cytometric analyses of ∆Ψ m , we demonstrated that ethanolic peel extract of Citrus sunki Hort. ex Tanaka (CPE) and its active compounds are capable of inducing a mild mitochondrial depolarization. Polymethoxylated flavones such as nobiletin and tangeretin were found as the active compounds responsible for CPE effects on ∆Ψ m . Neuronal viability was significantly increased in a dose‐dependent manner by CPE treatment in H 2 O 2 ‐stimulated HT‐22 cells as an in vitro neuronal insult model. CPE treatment significantly inhibited H 2 O 2 ‐induced apoptotic processes such as chromatin condensation, caspase 3 activation and anti‐poly (ADP‐ribose) polymerase (PARP) cleavage. CPE treatment significantly blocked mitochondrial calcium overload in H 2 O 2 ‐stimulated HT‐22 neurons as indicated by rhod‐2 acetoxymethyl ester. Taken together, our findings suggest that CPE and its active compounds may be considered as promising neuroprotective agents via inducing a mild mitochondrial depolarization. Copyright © 2012 John Wiley & Sons, Ltd.