Protective effects of flavonoids and two metabolites against oxidative stress in neuronal PC12 cells

Pavlica, Sanja; Gebhardt, Rolf

doi:10.1016/j.lfs.2009.10.017

Cited by 71 publications

(37 citation statements)

References 50 publications

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“…Since the previous review (Kell 2009a), I would draw particular attention to a comprehensive overview of the subject (Perron and Brumaghim 2009), as well as new reviews and papers on the chief polyphenol in green tea, (−) epigallocatechin-3-gallate (ChEBI 4806) (Adhami et al 2009; Butt and Sultan 2009; Hsieh et al 2009; Jimenez-Del-Rio et al 2010; Johnson et al 2010; Pandey and Gupta 2009; Paterniti et al 2009; Ramesh et al 2009; Reznichenko et al 2010; Suh et al 2009; Weinreb et al 2009a), on curcumin (ChEBI 3962) (a constituent of turmeric) (Aggarwal and Harikumar 2009; Aggarwal and Sung 2009; Anand et al 2010; Basile et al 2009; Epstein et al 2009; Hegde et al 2009; Iqbal et al 2009; Jiao et al 2009; Jurenka 2009; Kalpravidh et al 2010; Majumdar et al 2009; Messner et al 2009; Patil et al 2009; Ravindran et al 2009; Rivera-Espinoza and Muriel 2009; Thephinlap et al 2009; Thomas et al 2009; Tuntipopipat et al 2009; Wang et al 2009a), on eugenol (ChEBI 4917) (Nagababu et al 2010) (and cf. Allen and Cornforth 2009), on nepetoidin caffeic acid esters (Maioli et al 2010), on quercetin (ChEBI 16243) (Chobot 2010; Kitagawa et al 2009; Krukoski et al 2009; Lorrain et al 2010; Park et al 2010; Pavlica and Gebhardt 2010; Smirnova et al 2009; Terao 2009; Vlachodimitropoulou et al 2010) and on melatonin (CHEBI 16796) (Borah and Mohanakumar 2009; Korkmaz et al 2008, 2009; Reiter et al 2009; Sener et al 2009; Sharma and Haldar 2009; Signorini et al 2009). Many of the protective effects observed are likely due to the iron chelating, as well as directly antioxidative (redox) properties of these molecules (e.g.…”

Section: Catalytic Behaviour Of Polypeptides and Proteinsmentioning

confidence: 99%

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

2010

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Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions.

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Section: Catalytic Behaviour Of Polypeptides and Proteinsmentioning

confidence: 99%

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

2010

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“…353,354 There are many flavonoids reported to protect against oxidative stress in neuronal cell-lines and in some brain conditions in vivo . 355,356 Antioxidant mechanisms are considered to explain why some flavonoids protect against oxidative stress [quercetin ( 77 ), myricetin ( 105 ), luteolin ( 78 ), 357,358 hyperoside, 359 fisetin ( 142 ) 360 ] and β-amyloid-induced toxicity [puerarin, 361 genistein, 362 77 , 363 naringenin ( 79 ), 364 baicalein, baicalin 93 ] in neuronal cells in vitro , and against β-amyloid-induced cognitive impairments in vivo [silibinin 365 ]. Several synthetic lipophilic alkenylated 2,3-dehydrosilybin analogs of the flavolignan silibinin are neuroprotective against H 2 O 2 -induced toxicity in vitro and are being investigated for their pharmacological potential in CNS disorders.…”

Section: Antioxidant Natural Productsmentioning

confidence: 99%

Natural products as a source of Alzheimer's drug leads

2011

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“…They have multiple bioactive and neuroprotective effects, and exhibit anti-inflammatory activities in microglia [22–24]. Luteolin attenuates the neurotoxicities induced by peroxide [25], amyloid β (Aβ) protein [26] and 6-OHDA [27–29] in cell culture. In vivo treatment with luteolin protected mice brain from traumatic brain injury by inhibiting inflammatory response and inducing autophagy [30].…”

Section: Introductionmentioning

confidence: 99%

Luteolin and Apigenin Attenuate 4-Hydroxy-2-Nonenal-Mediated Cell Death through Modulation of UPR, Nrf2-ARE and MAPK Pathways in PC12 Cells

Yen

Kou

et al. 2015

PLoS ONE

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Luteolin and apigenin are dietary flavones and exhibit a broad spectrum of biological activities including antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. The lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE) has been implicated as a causative agent in the development of neurodegenerative disorders. This study investigates the cytoprotective effects of luteolin and apigenin against 4-HNE-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. Both flavones restored cell viability and repressed caspase-3 and PARP-1 activation in 4-HNE-treated cells. Luteolin also mitigated 4-HNE-mediated LC3 conversion and reactive oxygen species (ROS) production. Luteolin and apigenin up-regulated 4-HNE-mediated unfolded protein response (UPR), leading to an increase in endoplasmic reticulum chaperone GRP78 and decrease in the expression of UPR-targeted pro-apoptotic genes. They also induced the expression of Nrf2-targeted HO-1 and xCT in the absence of 4-HNE, but counteracted their expression in the presence of 4-HNE. Moreover, we found that JNK and p38 MAPK inhibitors significantly antagonized the increase in cell viability induced by luteolin and apigenin. Consistently, enhanced phosphorylation of JNK and p38 MAPK was observed in luteolin- and apigenin-treated cells. In conclusion, this result shows that luteolin and apigenin activate MAPK and Nrf2 signaling, which elicit adaptive cellular stress response pathways, restore 4-HNE-induced ER homeostasis and inhibit cytotoxicity. Luteolin exerts a stronger cytoprotective effect than apigenin possibly due to its higher MAPK, Nrf2 and UPR activation, and ROS scavenging activity.

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Protective effects of flavonoids and two metabolites against oxidative stress in neuronal PC12 cells

Cited by 71 publications

References 50 publications

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

Natural products as a source of Alzheimer's drug leads

Luteolin and Apigenin Attenuate 4-Hydroxy-2-Nonenal-Mediated Cell Death through Modulation of UPR, Nrf2-ARE and MAPK Pathways in PC12 Cells

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