Antioxidant Activity, Cellular Bioavailability, and Iron and Calcium Management of Neuroprotective and Nonneuroprotective Flavones

Published on Jan 1, 2015in Neurotoxicity Research3.311
· DOI :10.1007/s12640-014-9483-y
Carolina Echeverry10
Estimated H-index: 10
Florencia Arredondo10
Estimated H-index: 10
+ 3 AuthorsFederico Dajas20
Estimated H-index: 20
Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca2+ levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm. Oxidative cellular damage produced by H2O2 was prevented by all of the studied flavones with rather similar potency for all of them. Labile Iron Pool was neither affected by protective nor nonprotective flavones. Intracellular Ca2+ homeostasis was not affected by protective flavones either. Nonetheless, fisetin, the nonprotective flavone, decreased Ca2+ levels modifying Ca2+ homeostasis. Methylation of the catechol group, although weakens anti-oxidant capacity, keeps the neuroprotective capacity with less degradation and lower toxicity, constituting promising structural alternatives as leads for the design of neuroprotective molecules.
  • References (40)
  • Citations (7)
📖 Papers frequently viewed together
19 Citations
27 Citations
10 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Øyvind M. AndersenH-Index: 33
#2Kenneth R. Markham (University of Bergen)H-Index: 31
Separation and Quantification of Flavonoids A. Marston and K. Hostettmann Spectroscopic Techniques Applied to Flavonoids T. Fossen and O.M. Andersen Molecular Biology and Biotechnology of Flavonoid Biosynthesis K.M. Davies and K.E. Schwinn Flavonoids in Foods J.A.M. Kyle and G.G. Duthie Flavonoids in Wine V. Cheynier Dietary Flavonoids and Health - Broadening the Perspective M. Clifford and J.E. Brown Isoflavonoids and Human Health H. Wiseman Flavonoid Functions in Plants K.S. Gould and C. Liste...
765 Citations
Abstract Ethnopharmacological relevance Quercetin is a ubiquitous flavonoid that is present in numerous plants that are utilized in many different cultures for their nervous system and anticancer effects. To better understand the neuroprotective and antiproliferative activities of quercetin, we present a comprehensive review of the divergent actions that contribute to the ethnopharmacological profile of these plants. Results The pharmacological activities of quercetin that modulate antioxidation...
168 CitationsSource
#1Shen Li (PKU: Peking University)H-Index: 1
#2Xiao-Ping Pu (PKU: Peking University)H-Index: 15
In the present study, we investigated the neuroprotective effects of kaempferol in the mouse model of Parkinson's disease, which was induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We confirmed that MPTP led to behavioral deficits, depletion of dopamine and its metabolites, reduction in superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, and the elevation of malondialdehyde (MDA) levels in the substantia nigra. When administered prior to MPTP, kaem...
65 CitationsSource
#1María Pilar Almajano (UPC: Polytechnic University of Catalonia)H-Index: 14
#2I. Vila (UPC: Polytechnic University of Catalonia)H-Index: 1
Last. Silvia Ginés (University of Barcelona)H-Index: 23
view all 3 authors...
Tea is one of the most widely consumed beverages in the world and represents an important source of antioxidants mainly catechins that confer beneficial effects in reducing the risk of cardiovascular diseases, age-related disorders or cancer. In the central nervous system, oxidative stress caused by increased production of reactive oxygen and nitrogen species represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective eff...
35 CitationsSource
Abstract In this work we describe the protective effects of quercetin against H2O2 in 24-h-pretreated neuronal cultures. We explored quercetin availability and subcellular fate through the use of HPLC-Diode Array Detection (DAD), epifluorescence, and confocal microscopy. We focused on quercetin modulation of thiol-redox systems by evaluating changes in mitochondrial thioredoxin Trx2, the levels of total glutathione (GSH), and the expression of the γ-glutamate–cysteine ligase catalytic subunit (G...
112 CitationsSource
Quercetin shows structural features that have been related to the antioxidant potency of flavonoids and also shows neuroprotection in different models of oxidative death. Because only a few studies have focused on the flavonoid structural requirements for neuroprotection, this work evaluated the protective capacity of 13 flavones structurally related to quercetin, isolated from Kenyan plants, to rescue primary cerebellar granule neurons from death induced by a treatment with 24 h of hydrogen per...
34 CitationsSource
#1Thomas Walle (MUSC: Medical University of South Carolina)H-Index: 57
Dietary flavones have promising chemoprotective properties, in particular with regard to cancer, but problems with low oral bioavailability and sometimes unacceptable toxicity have made their use as protective additives to normal diets questionable. However, methylation of free phenolic hydroxyl groups leads to derivatives not susceptible to glucuronic acid or sulfate conjugation, resulting in increased metabolic stability. Methylation also leads to greatly improved transport through biological ...
63 CitationsSource
The neuroprotective actions of dietary flavonoids involve a number of effects within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. This multiplicity of effects appears to be underpinned by two processes. Firstly, they interact with important neuronal signalling cascades leading to an inhibition of apoptosis triggered by neurotoxic species an...
176 CitationsSource
#1Bernardino Ossola (UH: University of Helsinki)H-Index: 6
Last. Pekka T. Männistö (UH: University of Helsinki)H-Index: 44
view all 3 authors...
This review discusses the most recent data on the potential of quercetin to confer neuroprotection. Unfortunately, most of the in vitro studies have used quercetin aglycone, which is not detectable in the plasma or in the brain after oral intake. Moreover, quercetin metabolites and glycosides seem to be less neuroprotective and penetrate the BBB less efficiently than aglycone. Surprisingly, quercetin has beneficial effects on various in vivo models of neural disorders, particularly in cerebrovas...
89 CitationsSource
#1Hui Chang (Third Military Medical University)H-Index: 17
#2Mantian Mi (Third Military Medical University)H-Index: 30
Last. Jialin Yuan (Third Military Medical University)H-Index: 3
view all 9 authors...
Flavonoids exist extensively in the human diet, and a variety of health effects have been ascribed to them. The cytotoxic effects of 23 flavonoids on breast cancer cells (MDA-MB-231 and MCF-7), colorectal carcinoma cells (LoVo and DLD-1) and prostatic cancer cells (PC3) were investigated. By comparing the cytotoxicity (EC50) of selected molecules that differ in only one structure element, we identified several structural properties associated with enhanced cytotoxicity, including the presence of...
49 CitationsSource
Cited By7
#1Shushi Chen (NCYU: National Chiayi University)H-Index: 9
#1Wenjie Jian (SCAU: South China Agricultural University)H-Index: 4
Last. Yuanming Sun (SCAU: South China Agricultural University)H-Index: 21
view all 6 authors...
Abstract Konjac glucomannan (KGM) is an important source for preparation of Konjac oligo-glucomannan (KOG), but high molecular weight and viscosity in KGM inhibited its full degradation into KOG. In this study, KOG with a degree of polymerization between 2 and 9 was obtained by combining γ-irradiation and enzymatic hydrolysis in high yield. We investigated the protective effect of KOG against H2O2 - induced oxidative damage in vitro, using human hepatic cell line (LO2) as a cell model. Our resul...
#1Wenjie Jian (SCAU: South China Agricultural University)H-Index: 4
#2Liying Tu (JMU: Jimei University)H-Index: 1
Last. Yuanming Sun (SCAU: South China Agricultural University)H-Index: 21
view all 6 authors...
Abstract Konjac glucomannan (KGM) is an important functional polysaccharide in food research. However, unstable dispersibility of KGM inhibits its in-depth study and wide application. In this study, a degraded KGM (100 kGy-KGM), which showed excellent dispersibility and specific physicochemical properties, were obtained by γ-irradiation in a dosage of 100 kGy. We investigated the protective effect of 100 kGy-KGM against H 2 O 2 induced oxidative damage in LO2 cells. Our results demonstrated that...
9 CitationsSource
#1Ashfaq Ahmad (UPR-RP: UPRRP College of Natural Sciences)H-Index: 7
#2Tahir Ali (UPR-RP: UPRRP College of Natural Sciences)H-Index: 14
Last. Myeong Ok Kim (UPR-RP: UPRRP College of Natural Sciences)H-Index: 29
view all 6 authors...
Alzheimer’s disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ1–42 mouse model of AD. Single intracerebroventricular inject...
35 CitationsSource
#1Kathyani Parasram (U of W: University of Windsor)H-Index: 1
#1Myung-Soo ShonH-Index: 3
#2Ryeong-Hyeon KimH-Index: 2
Last. Gyo-Nam Kim (Kyungnam University)H-Index: 8
view all 8 authors...
Purpose: Although several physiological properties of fisetin have been reported, the potential of fisetin as a nutri-cosmetics material has been not considered. Therefore, anti-oxidant and anti-adipogenic effects in 3T3-L1 cells of fisetin were evaluated and its potential as a nutri-cosmetic ingredient was discussed. Methods: To test anti- oxidant activity of fisetin, ABTS radical scavenging assay was used and the cytotoxicity of fisetin in 3T3-L1 preadipocytes was evaluated by EZ-cytox assay. ...
2 CitationsSource
#1Harish C. Pal (UAB: University of Alabama at Birmingham)H-Index: 19
#2Ross L. Pearlman (UAB: University of Alabama at Birmingham)H-Index: 3
Last. Farrukh Afaq (UAB: University of Alabama at Birmingham)H-Index: 56
view all 3 authors...
Chronic inflammation is a prolonged and dysregulated immune response leading to a wide variety of physiological and pathological conditions such as neurological abnormalities, cardiovascular diseases, diabetes, obesity, pulmonary diseases, immunological diseases, cancers, and other life-threatening conditions. Therefore, inhibition of persistent inflammation will reduce the risk of inflammation-associated chronic diseases. Inflammation-related chronic diseases require chronic treatment without s...
15 CitationsSource
Abstract Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival pr...
33 CitationsSource