Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia

Yousuf, Seema; Atif, Fahim; Ahmad, Muzamil; Hoda, Nasrul; Ishrat, Tauheed; Khan, Badruzaman; Islam, Fakhrul

doi:10.1016/j.brainres.2008.10.068

Cited by 203 publications

(138 citation statements)

References 52 publications

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“…The present study demonstrated that treatment with quercetin has a far-reaching protective effect against the consequences of ischemic insults. A rat model of global cerebral I/R injury was used for the behavioral and biochemical tests, which is widely used to study the neuroprotective effect of quercetin, because it represents the biochemical and pathological features of stroke in humans, including oxidative stress, mitochondrial dysfunction and apoptosis (27). In response to the oxidative load in mitochondria, the outer membrane of mitochondria becomes permeabilized (7), resulting in the translocation of Bax from the cytosol to the mitochondria and the release of cytochrome c. Since delayed neuronal degeneration is mostly due to apoptosis, the present study further investigated the number of apoptotic cells by TUNEL staining.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway

Chao

Zhang

et al. 2015

Molecular Medicine Reports

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Abstract. The present study provided experimental evidence for the neuroprotective effects of quercetin using a rat model of global brain ischemic/reperfusion (I/R) injury. Pre-treatment with quercetin (5 or 10 mg/kg orally (p.o.); once daily) induced a dose-dependent reduction in I/R-induced hippocampal neuron cell loss, with 10 mg/kg/day being the lowest dose that achieved maximal neuroprotection. Administration of 10 mg/kg quercetin over at least 3 days prior to I/R was required to improve the survival rate of I/R rats. Fluorescence-assisted cell sorting, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling indicated neuronal cell loss in the CA1 hippocampus. Rats that had undergone transient global cerebral ischemia for 15 min followed by 1 h of reperfusion exhibited a significant increase in reactive oxygen species (ROS) production in the hippocampus. The I/R-induced ROS overproduction in the hippocampus at 1, 12 and 24 h following I/R was significantly decreased by quercetin pre-treatment. Western blot analysis revealed that the neuroprotective effects of quercetin (5 and 10 mg/kg/day, p.o.) were associated with an upregulation of the I/R-induced suppression of B-cell lymphoma-2 (Bcl-2), Bcl extra large and survivin expression as well as phosphorylation of Bcl-2-associated death promoter. Furthermore, the neuroprotective effects of quercetin (5, 10 mg/kg/day) in the brain were associated with an upregulation of Akt signaling. These findings suggested that the inhibition of I/R-induced brain injury by quercetin likely involves a transcriptional mechanism to enhance anti-apoptotic signaling.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway

Chao

Zhang

et al. 2015

Molecular Medicine Reports

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“…Resveratrol has been proposed as a neuroprotective agent in the pathophysiological process of I/R injury, and this function may be associated with its anti-oxidative and anti-inflammatory effects (12,13). However, the mechanism by which resveratrol confers neuroprotection in cerebral ischemia remains to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol ameliorates oxidative stress and inhibits aquaporin 4 expression following rat cerebral ischemia-reperfusion injury

Tan

Liu

et al. 2015

Molecular Medicine Reports

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Abstract. Cerebral ischemia-reperfusion (I/R) is associated with increased levels of reactive oxygen species (ROS) and brain edema, which lead to the deterioration of patient prognosis. Resveratrol serves a neuroprotective role in I/R injury, and this role may be associated with its anti-oxidative effects. However, resveratrol's mechanism of action in cerebral I/R injury remains to be fully understood. In order to investigate the effect of resveratrol in cerebral I/R-induced injury, male Sprague-Dawley rats were randomly assigned to four groups: The sham-operation group, the I/R group and the edaravone and resveratrol groups (I/R + E and I/R + R groups). Infarct volume was evaluated by 2,3,5-tripenyltetrazolium chloride staining, brain edema was evaluated by the water content in the reperfused brain and malondialdehyde (MDA) was measured by the thiobarbituric acid method. Superoxide dismutase (SOD) levels were measured using the Total Superoxide Dismutase Assay kit. Inducible nitric oxide synthase (iNOS) levels in the hippocampus and cortex were measured by ELISA, and aquaporin 4 (AQP4) expression was measured by immunohistochemical staining and western blot analysis. The results demonstrated that resveratrol reduced the infarct volume and the incidence of brain edema and reduced neurological deficits. These outcomes were accompanied by reduced levels of MDA, iNOS and AQP4, and increased SOD levels in cerebral I/R injury. In conclusion, resveratrol protected against cerebral I/R injury by ameliorating oxidative stress and reducing AQP4 expression.

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“…Hence, we sought to assess the protective efficacy of MF against HIE by evaluating the cerebral infarct size, edema, lipid peroxidation (MDA), antioxidant status and inflammatory markers in neonatal pups. Typically, the neuronal damage during ischemic condition is evaluated by assessing the area/size of brain infarction by TTC staining method (Yousuf et al, 2009). The fundamental principle of the TTC staining technique is based on the activation of mitochondrial cytochrome oxidase enzyme in the viable (neuronal) cells to produce a red color.…”

Section: Discussionmentioning

confidence: 99%

Neurotherapeutic effect of mangiferin against hypoxic–ischemic encephalopathy in neonatal rats

Lv¹,

Wang²,

Hu³

et al. 2016

Afr. J. Trad. Compl. Alt. Med.

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Background: Hypoxic-ischemic encephalopathy (HIE) in perinatal condition is highly associated with mortality and several neurological disabilities. The present experiment was blueprinted to ascertain the protective efficacy of mangiferin (MF) against hypoxic-ischemic brain injury in neonatal rats. Materials and Methods: Fourth six neonatal rats (pups) were randomly separated into four groups as a sham group that received only water (control; n=12), pups exposed to Hypoxic-ischemic (HI) insult (HI group-II; n=11), pups receiving 20 (MF 20+HI-III; n=11) or 40 (MF 40+HI-IV; n=12) mg/kg b. wt of MF dissolved in water via i.p. for 7 consecutive days as pretreatment regimen before HI insult as well as one-time post treatment after HI insult. Results: MF pretreatment for seven days considerably attenuated the cerebral infarct size, edema level, lipid peroxidation (MDA), inflammatory markers (TNF-α, IL-1β, IL-6, and NF-p65 subunit) as well as greatly ameliorated the antioxidant activities of catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSH) and thereby maintaining the redox balance. The number of viable neuronal count (nissl bodies) was exponentially increased on administration with both the dosages of MF. Both the dosages showed substantial protection against HIE, however, 40 mg of MF exhibit superior neuroprotection in equivalence with 20 mg of MF. Conclusion:The results of the present study distinctly proving the beneficial effect of MF against HIE by concomitantly improving neuronal count and antioxidant status. Hence, we recommend MF might be used for treating neonatal HIE with some standard drugs.

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Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia

Cited by 203 publications

References 52 publications

Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway

Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway

Resveratrol ameliorates oxidative stress and inhibits aquaporin 4 expression following rat cerebral ischemia-reperfusion injury

Neurotherapeutic effect of mangiferin against hypoxic–ischemic encephalopathy in neonatal rats

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