Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves
- Title
- Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves
- Author
- 김철영
- Keywords
- glutamate-induced oxidative cell death; Dendropanax morbifera leaves; isoquercitrin; quercetin; nuclear factor erythroid 2-related factor 2; heme oxygenase-1; synergism
- Issue Date
- 2021-04
- Publisher
- MDPI
- Citation
- ANTIOXIDANTS, v. 10, NO 4, Page. 1-24
- Abstract
- Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat
diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse
hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective
ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were
isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and
rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial
superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of
apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear
factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of
Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations
in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin
and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction
analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing
the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.
- URI
- https://www.proquest.com/docview/2528297549?accountid=11283https://repository.hanyang.ac.kr/handle/20.500.11754/171758
- ISSN
- 20763921
- DOI
- 10.3390/antiox10040554
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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