Resveratrol neuroprotection in stroke and traumatic CNS injury

Lopez, Mary S.; Dempsey, Robert J.; Vemuganti, Raghu

doi:10.1016/j.neuint.2015.08.009

Cited by 140 publications

(82 citation statements)

References 147 publications

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“…Resveratrol is also able to increase the quantity and function of mitochondria (15). Previous studies have demonstrated that various organs, such as the liver, brain, kidney and lung, in F2 hybrid mice appear to have oxidative DNA damage with aging (12,16,17). However, the oral absorption of resveratrol may reduce the high levels of oxidative damage markers induced by aging (18).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

2017

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Abstract. The aim of the present study was to determine the protective effects of resveratrol on a rat model of osteoporosis and examine the associated mechanisms of its action. Rats were randomized into the following groups: Control, osteoporosis, osteoporosis + low-dose resveratrol, osteoporosis + middle-dose resveratrol and osteoporosis + high-dose resveratrol groups. Resveratrol treatment was administered 7 days after surgery for 8 weeks. ELISA assay was used to analyze alkaline phosphatase (ALP) and osteocalcin (OC) protein levels. Western blotting was performed to assess the protein expression of sirtuin 1 (SIRT1), nuclear factor (NF)-κB and NF-κB inhibitor (IkB) α. In the present study, the results indicated that resveratrol markedly improved the bone mineral density value, femoral porosity and bone mechanical tests in osteoporosis rats. Administration of resveratrol significantly decreased the serum levels of ALP and OC in rats with osteoporosis. Finally, treatment with resveratrol significantly promoted the protein expression of SIRT1, suppressed NF-κB and activated the IkBα protein expression in rats with osteoporosis. In conclusion, treatment with resveratrol significantly improved the final body weight of the osteoporosis rats via the SIRT1-NF-κB signaling pathway. The present study suggested that resveratrol exerted a protective effect on osteoporosis through activation of the SIRT1-NF-κB signaling pathway in rats.

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Section: Introductionmentioning

confidence: 99%

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

2017

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“…Interestingly, all of these pathophysiologic mechanisms also mediate poststroke neuronal death (Kim and Vemuganti, 2015; Lopez et al, 2015; Nakka et al, 2016). A recent study showed that α -Syn transgenic mice are more susceptible to ischemic brain damage (Unal-Cevik et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Poststroke Induction of -Synuclein Mediates Ischemic Brain Damage

Kim

Mehta²,

Kaimal³

et al. 2016

Journal of Neuroscience

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α-Synuclein (α-Syn), one of the most abundant proteins in the CNS, is known to be a major player in the neurodegeneration observed in Parkinson's disease. We currently report that transient focal ischemia upregulates α-Syn protein expression and nuclear translocation in neurons of the adult rodent brain. We further show that knockdown or knock-out of α-Syn significantly decreases the infarction and promotes better neurological recovery in rodents subjected to focal ischemia. Furthermore, α-Syn knockdown significantly reduced postischemic induction of phospho-Drp1, 3-nitrotyrosine, cleaved caspase-3, and LC-3 II/I, indicating its role in modulating mitochondrial fragmentation, oxidative stress, apoptosis, and autophagy, which are known to mediate poststroke neuronal death. Transient focal ischemia also significantly upregulated serine-129 (S129) phosphorylation (pα-Syn) of α-Syn and nuclear translocation of pα-Syn. Furthermore, knock-out mice that lack PLK2 (the predominant kinase that mediates S129 phosphorylation) showed better functional recovery and smaller infarcts when subjected to transient focal ischemia, indicating a detrimental role of S129 phosphorylation of α-Syn. In conclusion, our studies indicate that α-Syn is a potential therapeutic target to minimize poststroke brain damage.

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“…Resveratrol is a potential drug candidate for treatment of ischemic stroke, as summarized in a recent review article [126]. Resveratrol exhibited multiprotective effects, such as antiapoptotic [127,128], antioxidative [129], anti-inflammatory [130] and antiexcitotoxic effects [131,132]. Resveratrol has a therapeutic time window up to 6 h after ischemic onset; it reduced infarct volume, attenuated microglial activation and suppressed cytokine production and free radical generation [130].…”

Section: Active Compounds From Chinese Herbal Medicine For Targeting mentioning

confidence: 99%

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

Chen¹,

Guan²,

Shen³

2016

Integr Med Int

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Stroke is the leading cause of death and disability worldwide, and ischemic stroke accounts for more than 85% of the stroke incidence. Tissue plasminogen activator (t-PA) is the only FDA-approved drug for ischemic stroke treatment with a narrow treatment time window of 4.5 h. Hemorrhagic transformation (HT) is a severe complication of delayed t-PA treatment in ischemic stroke. Thus, it is critically important to develop combination therapies to reduce HT and extend the therapeutic time window of t-PA. Current progress suggests that peroxynitrite (ONOO^-)/high-mobility group box 1 protein (HMGB1)/matrix metalloproteinase-9 (MMP-9) signaling cascades could be important for attenuating HT during thrombolytic treatment for acute ischemic stroke. Recently, important progress has been made in seeking for natural compounds from Chinese medicine for reducing ischemic stroke injury, with some of them targeting ONOO^-/HMGB1/MMP-9 signaling cascades. Herein, we analyze the roles and interactions of these three targets in mediating HT; subsequently, we summarize the potential compounds from Chinese herbal medicine for attenuating HT and analyze the related targets. Finally, we raise the potential issues to be addressed in further development of these compounds as combination therapy.

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Resveratrol neuroprotection in stroke and traumatic CNS injury

Cited by 140 publications

References 147 publications

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

Poststroke Induction of -Synuclein Mediates Ischemic Brain Damage

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

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