Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress: The role in the interruptive apoptotic signal

Miyoshi, Noriyuki; Naniwa, Kisa; Yamada, Takayo; Osawa, Toshihiko; Nakamura, Yoshimasa

doi:10.1016/j.abb.2007.07.026

Cited by 61 publications

(34 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34) In other studies, apigenin was shown to have a prooxidant effect in a normal trout liver cell line and the HL-60 cell line. 35,36) Thus, apigenin appears to have different biological effects in different cell types. The mechanism through which apigenin exerts these cell-specific effects remains to be clarified.…”

Section: Resultsmentioning

confidence: 99%

Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Suh

Woo

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Glucose toxicity contributes to progressive β-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic β-cells. We investigated whether the flavonoid apigenin protects pancreatic β-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic β-cells were cultured with or without apigenin in the presence of dRib. Time-and dosedependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨ m ) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2′,7′-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨ m , while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib-induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic β-cells via oxidative stressrelated signaling. Key words oxidative stress; apigenin; 2-deoxy-D-ribose; diabetes; pancreatic β-cellOxidative stress is known to be a major contributor to the development of overt diabetes and its associated complications.1) Oxidative stress results from a persistent imbalance between antioxidant defenses and the production of highly reactive oxygen species (ROS).2) ROS are normal byproducts of cellular metabolism. However, a marked increase in glucose metabolism could lead to excessive ROS production, which could contribute to the development of diabetic complications. In particular, pancreatic β-cells express low levels of antioxidant enzymes and do not up-regulate these enzymes upon exposure to high concentrations of glucose.3) Thus, increased ROS production in the presence of low antioxidant defense levels could result in ROS accumulation, which would lead to the oxidative pancreatic β-cell damage that is partly responsible for diabetes. Nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) are 2 redox-sensitive transcription factors that can be regulated by oxidative stress. [4][5][6] By activating these transcription factors in isolated peripheral mononuclear cells of diabetic patients, ROS are also involved in the pathogenesis of diabetic nephropathy. 7) In addition, activation of NF-κB correlates with the quality of glycemic control and has been shown to be reduced by treatment with antioxidants in a diabetic animal model and diabetic pa...

show abstract

Section: Resultsmentioning

confidence: 99%

Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Suh

Woo

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…When HL-60 cells were treated with MPO inhibitors, the ROS level enhanced by apigenin was significantly reduced. The gathered data suggested that MPO-catalyzed production of apigenin B-ring phenoxyl radicals might be responsible for the prooxidant effect (Miyoshi et al, 2007). Another study also indicated the prooxidant activity of polyphenols arising from their interactions with metals such as iron and cupper led to the production of hydroxyl radicals (Perron & Brumaghim, 2009).…”

Section: Pharmaceutical Biologymentioning

confidence: 93%

Investigation of STW 5 (Iberogast®) preventive effects in experimental sepsis

Dadkhah

Fatemi

Ashrafihelan

2013

Pharmaceutical Biology

View full text Add to dashboard Cite

“…When these cells were treated with MPO inhibitors, the ROS level enhanced by apigenin was significantly reduced. The gathered data suggested that oxidation of apigenin by MPO and production of B-ring phenoxyl radicals might be responsible for the prooxidant effects (Miyoshi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Heart and kidney oxidative stress status in septic rats treated with caraway extracts

Dadkhah

Fatemi²

2011

Pharmaceutical Biology

View full text Add to dashboard Cite

Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress: The role in the interruptive apoptotic signal

Cited by 61 publications

References 48 publications

Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Investigation of STW 5 (Iberogast®) preventive effects in experimental sepsis

Heart and kidney oxidative stress status in septic rats treated with caraway extracts

Contact Info

Product

Resources

About