Preventive Effect of 7,8-Dihydroxyflavone against Oxidative Stress Induced Genotoxicity

Zhang, Rui; Kang, Kyoung Ah; Piao, Mei Jing; Ko, Dong Ok; Wang, Zhi Hong; Chang, Weon Young; You, Ho Jin; Lee, In Kyung; Kim, Bum Joon; Kang, Sam Sik; Hyun, Jin Won

doi:10.1248/bpb.32.166

Cited by 46 publications

(42 citation statements)

References 29 publications

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“…Recently, 7,8-DHF has been reported to have neurotrophic activities in various neurological diseases, such as stroke and Parkinson's disease (27). Although several studies on the antioxidant effects of 7,8-DHF have been carried out (18,29,30), the molecular mechanisms underlying its anti-inflammatory effects have yet to be reported.…”

Section: 8-dihydroxyflavone Exhibits Anti-inflammatory Propertiesmentioning

confidence: 99%

7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells

et al. 2012

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Abstract. 7,, a member of the flavonoid family, has received considerable attention as a selective tyrosine kinase receptor B agonist. Several studies have indicated that 7,8-DHF has neurotrophic and antioxidant activities. However, little is known about the cellular and molecular mechanisms underlying the anti-inflammatory activity of 7,8-DHF. Therefore, we investigated whether 7,8-DHF affects the expression of inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Our results indicated that 7,8-DHF significantly attenuated secretion of LPS-induced inflammatory mediators nitric oxide (NO), prostaglandin E 2 (PGE 2 ) and interleukin-1β (IL-1β) in RAW264.7 cells. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and IL-1β was decreased by pre-treatment with 7,8-DHF. Our results also showed that 7,8-DHF reduces LPS-induced nuclear factor-κB (NF-κB) activity via the suppression of the nuclear translocation of NF-κB p65 and the degradation of inhibitor κB (lκB). In addition, 7,8-DHF inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular-signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). These results suggest that the anti-inflammatory property of 7,8-DHF is related to the downregulation of iNOS, COX-2 and IL-1β, due to NF-κB inhibition as well as to the negative regulation of MAPK activation in RAW264.7 cells. Thus, 7,8-DHF may be a novel therapeutic agent for the prevention of various inflammatory diseases.

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Section: 8-dihydroxyflavone Exhibits Anti-inflammatory Propertiesmentioning

confidence: 99%

7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells

et al. 2012

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“…Large quantitites of 8-OhdG are produced in mammalian cells, either as a by-product of normal oxidative metabolism or as a result of exogenous sources of ROS (Zhang et al 2009a;2009b). During DNA replication, 8-OhdG mismatches with adenosine, giving rise to a G:C to T:A transversion mutation that damages active genes in cells, resulting in induction of cell loss (Hyun et al 2000;2003).…”

mentioning

confidence: 99%

“…Recently, antioxidant compounds such as luteolin, quercetin, rosmarinic acid, butin, and 7,8-dihydroxyflavone were shown to enhance oxidative DNA damage protection and repair (Silva et al 2008;Kang et al 2009;Zhang et al 2009a), suggesting these compounds may protect against oxidative stress-induced DNA damage, which occurs in several pathological conditions such as Alzheimer's disease, cancer, and hypertension (Zana et al 2006;Thompson 2006;Subash et al 2010).…”

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confidence: 99%

Triphlorethol-A Improves the Non-Homologous End Joining and Base-Excision Repair Capacity Impaired by Formaldehyde

Zhang

Kang

Piao

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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“…This compound has been reported to display significant neurotrophic and anti-oxidant activity (13,(15)(16)(17). However, the precise mechanism of the anti-cancer effect of 7,8-DHF is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…1) is a selective tyrosine kinase receptor B (TrkB) agonist that can pass the blood-brain barrier (13)(14)(15). Several studies have shown that 7,8-DHF has neurotrophic and anti-oxidant activity (13,(15)(16)(17). Nevertheless, no studies have investigated the molecular mechanisms underlying its anti-cancer effects.…”

Section: Introductionmentioning

confidence: 99%

7,8-dihydroxyflavone induces G1 arrest of the cell cycle in U937 human monocytic leukemia cells via induction of the Cdk inhibitor p27 and downregulation of pRB phosphorylation

et al. 2012

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Abstract. We investigated the mechanisms of the anti-proliferative action of 7,8-dihydroxyflavone (7,8-DHF), a member of the flavonoid family, in U937 human monocytic leukemia cells. We found that 7,8-DHF time-dependently inhibited the growth of U937 cells, arresting them in the G1 phase of their cell cycle and inducing apoptosis. 7,8-DHF-induced G1 arrest was correlated with downregulation of cyclin E, with a concomitant upregulation of cyclin-dependent kinase (Cdk) inhibitors including p27, and association of p27 with Cdk2 was markedly induced in 7,8-DHF-treated cells. We also observed that downregulation of the phosphorylation of retinoblastoma protein (pRB) by this flavonoid was associated with enhanced binding of pRB and the transcription factor E2F-1. Overall, our results demonstrate a combined mechanism for the anticancer effects of 7,8-DHF that involves the inhibition of pRB phosphorylation and induction of p27 as targets for 7,8-DHF.

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Preventive Effect of 7,8-Dihydroxyflavone against Oxidative Stress Induced Genotoxicity

Cited by 46 publications

References 29 publications

7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells

7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells

Triphlorethol-A Improves the Non-Homologous End Joining and Base-Excision Repair Capacity Impaired by Formaldehyde

7,8-dihydroxyflavone induces G1 arrest of the cell cycle in U937 human monocytic leukemia cells via induction of the Cdk inhibitor p27 and downregulation of pRB phosphorylation

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