Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells

Shirai, Mutsuko; Kawai, Yoshichika; Yamanishi, Rintaro; Kinoshita, Takashi; Chuman, Hiroshi; Terao, Junji

doi:10.1080/10715760600794287

Cited by 61 publications

(40 citation statements)

References 29 publications

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“…Quercetin 3-O-b-glucuronide was less effective than quercetin in suppressing the formation of oxygen species and was not taken up into differentiated PC12 cells. 34) Thus, quercetin not its metabolites appears to be effective in our study, although the cellular responses (death and survival) were different.…”

Section: Discussionmentioning

confidence: 91%

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Sasaki

Nakamura

Tsuchiya

et al. 2007

Biological & Pharmaceutical Bulletin

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Flavonoids, a large group of polyphenolic compounds found in fruits and vegetables, have attracted much attention because of their broad pharmacological, particularly antioxidative, activities.1,2) Flavonoids may exert beneficial effects on a number of disease states including cancer, cardiovascular disease, inflammation and neurodegenerative disorders. 1,2)The pathology of neurodegenerative disorders including Alzheimer's disease and aging is associated with oxidative stress caused by reactive oxygen species and reactive nitrogen species.2,3) If oxidative stress is suppressed by compounds in foods, such as flavonoids, this may act as a preventive measure to reduce damage and/or disfunction of cells. Quercetin (3,3Ј,4Ј,5,, which possesses a wide spectrum of pharmacological and biological properties, 2,4) is found in many kinds of food. The daily Western diet contains on average about 25 mg of various flavonoids, of which quercetin is a major ingredient (16 mg/d).5) Quercetin can scavenge free radicals directly and inhibit the oxidation of various molecules resulting in the activation of antioxidant defense pathways in vivo and in vitro. However, the actions of flavonoids are complex and paradoxical in some cases. Several studies have shown that quercetin is a pro-oxidant and cytotoxic in leukemic cells. 7,8) Flavonoids including quercetin caused apoptosis in carcinoma/cancer cells 2,9) and showed cytotoxicity in normal cells including human umbilical vein endothelial cells.10) The neuronal density of the hippocampus in gerbils subjected to infusion of quercetin to the ventricle was significantly lower than that in control.11) Thus, the effects of quercetin on cell death and/or apoptosis in cells including neuronal cells have not been well confirmed.The PC12 cell line, a rat adrenal medullary pheochromocytoma, is a useful model for studying the survival of neuronal cells. Native PC12 cells divide and resemble precursors of adrenal chromaffin cells and sympathetic neurons when grown in the presence of serum, and gradually attain the phenotypic properties of sympathetic neurons on the addition of nerve growth factor (NGF). Previously, we reported that the treatment of native and undifferentiated PC12 cells with an inhibitor of thioredoxin reductase and dopaminergic neurotoxins such as 1-methyl-4-phenylpyridinium ion (MPP ϩ ) caused apoptosis via a caspase-mediated pathway. 12,13) Quercetin has been shown to inhibit cell death and/or apoptosis induced by various stimuli including oxidative stress and MPP ϩ in differentiated PC12 cells. [14][15][16] In undifferentiated PC12 cells, however, antioxidants including quercetin did not have a protective effect against cell death induced by oxidative stress including MPP ϩ . 15,16) The effect of quercetin on cell survival and death in undifferentiated PC12 cells has not been well established. In the present study, we investigated whether quercetin causes cell death in undifferentiated PC12 cells or not. The effect of genistein, a soy isoflavone that has the pro-apoptotic ac...

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Section: Discussionmentioning

confidence: 91%

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Sasaki

Nakamura

Tsuchiya

et al. 2007

Biological & Pharmaceutical Bulletin

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“…As with G7G, D7G was less effective than its aglycone, daidzein, but was equally effective as daidzin (156% delays in lag phase) in inhibiting lipid oxidation. It is worth noting that flavonol glycosides were also less active than their aglycones in the inhibition of lipid oxidation in micelles [49], human LDL [50] and red blood cells [51], and against free radical-induced oxidative haemolysis in red blood cells [52,53].…”

Section: Effect Of Genistein-and Daidzein-7-o-b-dglucuronide On the Lmentioning

confidence: 99%

Genistein‐ and daidzein 7‐O‐β‐D‐glucuronic acid retain the ability to inhibit copper‐mediated lipid oxidation of low density lipoprotein

Kgomotso

Chiu

Ng³

2008

Molecular Nutrition Food Res

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Two isoflavones in vivo metabolites, genistein-7-O-beta-D-glucuronic acid (G7G) and daidzein-7-O-beta-D-glucuronic acid (D7G) were synthesised chemically. The ability of these metabolites to scavenge an organic radical was measured by the trolox equivalent antioxidant capacity (TEAC) assay, while their reducing ability was measured by the ferric reducing antioxidant power (FRAP) assay. The TEAC and FRAP values of G7G were 45 and 51% of that of genistein, while those of D7G were 52 and 77% of that of daidzein, respectively. A direct assessment of G7G and D7G antioxidant activity by their ability to delay copper(II)-mediated lipid oxidation of human LDL showed that these metabolites retained the ability to prevent oxidation in the lipid phase, but activity was diminished compared to their corresponding aglycones. However, G7G and D7G also decreased the rate of lipid oxidation to 53 and 86% of control without isoflavones, respectively, indicating a continuous exchange of antioxidants between the aqueous environment and the LDL lipid phase during the whole oxidation period.

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“…PC-12 cells are a valid in vitro model for investigating the antioxidative effect on neurons [22, 23]. However, to verify the ability of SK-119 to attenuate oxidative stress or cell protection, the use of additional physiologically relevant systems was of interest.…”

Section: Resultsmentioning

confidence: 99%

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

Kahremany

Babaev

Gvirtz

et al. 2019

Skin Pharmacol Physiol

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Background/Aims: The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. Methods: SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Results: The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. Conclusion: These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress.

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Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells

Cited by 61 publications

References 29 publications

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Genistein‐ and daidzein 7‐O‐β‐D‐glucuronic acid retain the ability to inhibit copper‐mediated lipid oxidation of low density lipoprotein

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

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