Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity

Han, Xiaohua; Zhu, Shaolei; Wang, Bingxiang; Chen, Lei; Ran, Li; Yao, Weicheng; Qu, Zhe

doi:10.1016/j.neuint.2013.10.018

Cited by 78 publications

(45 citation statements)

References 29 publications

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“…Our data support the notion that TrkB-induced activation of PI3K/Akt plays an important role in rescuing neurons from traumatic insults. However, previous studies have suggested that 7,8-DHF can induce neuroprotection through its antioxidant action in vitro [38], [39]. The beneficial effects of 7,8-DHF may be attributed in part to the prevention of free radical and oxidant formation.…”

Section: Discussionmentioning

confidence: 96%

Post-Injury Treatment with 7,8-Dihydroxyflavone, a TrkB Receptor Agonist, Protects against Experimental Traumatic Brain Injury via PI3K/Akt Signaling

Hung

Chen

et al. 2014

PLoS ONE

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Tropomyosin-related kinase B (TrkB) signaling is critical for promoting neuronal survival following brain damage. The present study investigated the effects and underlying mechanisms of TrkB activation by the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) on traumatic brain injury (TBI). Mice subjected to controlled cortical impact received intraperitoneal 7,8-DHF or vehicle injection 10 min post-injury and subsequently daily for 3 days. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed. The protective effect of 7,8-DHF was also investigated in primary neurons subjected to stretch injury. Treatment with 20 mg/kg 7,8-DHF attenuated functional deficits and brain damage up to post-injury day 28. 7,8-DHF also reduced brain edema, neuronal death, and apoptosis at day 4. These changes were accompanied by a significant decrease in cleaved caspase-3 and increase in Bcl-2/Bax ratio. 7,8-DHF enhanced phosphorylation of TrkB, Akt (Ser473/Thr308), and Bad at day 4, but had no effect on Erk 1/2 phosphorylation. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels and promoted cAMP response element-binding protein (CREB) activation. This beneficial effect was attenuated by inhibition of TrkB or PI3K/Akt. 7,8-DHF also promoted survival and reduced apoptosis in cortical neurons subjected to stretch injury. Remarkably, delayed administration of 7,8-DHF at 3 h post-injury reduced brain tissue damage. Our study demonstrates that activation of TrkB signaling by 7,8-DHF protects against TBI via the PI3K/Akt but not Erk pathway, and this protective effect may be amplified via the PI3K/Akt-CREB cascades.

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Section: Discussionmentioning

confidence: 96%

Post-Injury Treatment with 7,8-Dihydroxyflavone, a TrkB Receptor Agonist, Protects against Experimental Traumatic Brain Injury via PI3K/Akt Signaling

Hung

Chen

et al. 2014

PLoS ONE

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“…In the present study, we have shown that the TrkB receptor agonist DHF preferentially potentiates hippocampal MF‐CA3 synaptic transmission in a TrkB receptor‐independent manner. In addition to the TrkB agonist action, DHF has been known to have TrkB‐independent antioxidant activity . While the robust synaptic potentiation observed here is unlikely to result from the antioxidant effect of DHF, these effects might share signaling pathways.…”

Section: Discussionmentioning

confidence: 75%

“…In addition to the TrkB agonist action, DHF has been known to have TrkB-independent antioxidant activity. [24][25][26] While the robust synaptic potentiation observed here is unlikely to result from the antioxidant effect of DHF, these effects might share signaling pathways. Although the exact mechanism mediating the DHF-induced synaptic potentiation remains unknown, it was found to be sensitive to 2-APB below 10 μmol/L.…”

Section: Discussionmentioning

confidence: 80%

Synapse‐selective rapid potentiation of hippocampal synaptic transmission by 7,8‐dihydroxyflavone

Kobayashi

Suzuki

2018

Neuropsychopharm Rep

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Aim The identification of 7,8‐dihydroxyflavone (DHF) as a small molecule agonist for tropomyosin‐related kinase B (TrkB) facilitated understanding of the role of TrkB signaling in regulating higher brain functions. DHF can penetrate the blood‐brain barrier after systemic administration and changes the performance of cognitive and emotional behavioral tasks. However, it is poorly understood how DHF modulates neuronal functions at cellular levels. Aiming to understand the cellular basis underlying DHF‐induced modifications of the brain functions, we examined the effects of DHF on the hippocampal excitatory synaptic transmission. Methods Field excitatory postsynaptic potentials were recorded using hippocampal slices prepared from adult male mice. Effects of bath‐applied DHF on the synaptic efficacy were examined. Results We found that DHF induced robust synaptic potentiation at the mossy fiber to CA3 synapse. DHF had minimal effects at other hippocampal excitatory synapses or at immature mossy fiber synapse in juvenile mice. The TrkB receptor blockers K252a and ANA‐12 did not affect the DHF‐induced synaptic potentiation. Drug screening revealed that relatively low concentrations of 2‐aminoethoxydiphenylborane blocked the DHF‐induced synaptic potentiation. Conclusion Our results demonstrate that DHF selectively potentiates hippocampal mossy fiber synaptic transmission via a TrkB receptor‐independent mechanism. This novel neuromodulatory effect of DHF may influence higher brain functions by itself or together with the activation of the TrkB receptor. The rapid induction of the potentiation implies its potential importance in the acute behavioral effects of DHF.

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“…The level of Dcm in HLE cells was measured using Rhodamine123 (Rh123), a specific fluorescent probe for monitoring the membrane potential in living cells as previously described (Han et al 2014). After exposure to H 2 O 2 (250 mM) and/or indicated concentrations of nSA for 6 h, the cells were washed twice with PBS and incubated with Rh123 (1 mM) for 30 min at 37 C. The fluorescent intensity was analysed with an excitation/emission wavelength at 507/ 529 nm on a flow cytometry (Becton Dickinson, San Jose, CA).…”

Section: Measurement Of Mitochondrial Membrane Potential (Dcm)mentioning

confidence: 99%

Protective effects of Semiaquilegia adoxoides n-butanol extract against hydrogen peroxide-induced oxidative stress in human lens epithelial cells

Liu

Wei

Wang

et al. 2016

Pharmaceutical Biology

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Context Hydrogen peroxide (H 2 O 2 )-induced damage in the lens epithelium leads to cell death and cataract. Semiaquilegia adoxoides (DC.) Makino (Ranunculaceae), a folk medicine of Hmong (an ethnic group of China), has been traditionally used to treat cataract; however, the underlying molecular mechanism is yet to be uncovered. Objective This study aimed to investigate whether the n-butanol extract of S. adoxoides (nSA) is effective against the H 2 O 2 -induced oxidative stress in human lens epithelial (HLE) cells. Materials and methods Human lens epithelial (SRA 01/04) cells were stimulated by H 2 O 2 (250 mM) in the presence or absence of nSA. The antioxidant effects of nSA were determined in terms of cell viability (MTT assay), apoptosis (AnnexinV/PI staining), radical scavenging capability (various enzymatic assays), loss of mitochondrial membrane potential (Rhodamine 123 staining), expression of apoptotic markers including caspase-3 and caspase-9 and the change of Bcl-2/Bax ratio (western blot) in the HLE cells.Results The results showed that pretreatment of nSA (250, 500 and 1000 mg/mL) markedly reduced H 2 O 2 -induced cellular apoptosis and malondialdehyde accumulation, but elevated the activities of total superoxide dismutase, catalase, glutathione peroxidase. Thus, the total antioxidative capability was enhanced upon the nSA treatment meanwhile the loss of mitochondrial membrane potential was prevented. Moreover, nSA at concentrations of 250, 500 and 1000 mg/mL also significantly suppressed the activation of caspase-3 and -9, and increased the Bcl-2/Bax ratio in the HLE cells. Discussion and conclusion Our findings suggested that nSA is a potential prophylactic agent in the prevention of cataractogeneis. ARTICLE HISTORY

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Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity

Cited by 78 publications

References 29 publications

Post-Injury Treatment with 7,8-Dihydroxyflavone, a TrkB Receptor Agonist, Protects against Experimental Traumatic Brain Injury via PI3K/Akt Signaling

Post-Injury Treatment with 7,8-Dihydroxyflavone, a TrkB Receptor Agonist, Protects against Experimental Traumatic Brain Injury via PI3K/Akt Signaling

Synapse‐selective rapid potentiation of hippocampal synaptic transmission by 7,8‐dihydroxyflavone

Protective effects of Semiaquilegia adoxoides n-butanol extract against hydrogen peroxide-induced oxidative stress in human lens epithelial cells

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