Is chronic curcumin supplementation neuroprotective against ischemia for antioxidant activity, neurologic deficit score, or neuronal apoptosis in an experimental stroke model?

Altınay, Serdar; Çabalar, Murat; İşler, Cihan; Yıldırım, Funda; Çelik, Duygu Sultan; Zengi, Oğuzhan; Taş, Abdurrahim; Gülçubuk, Ahmet

doi:10.5137/1019-5149.jtn.17405-16.0

Cited by 16 publications

(14 citation statements)

References 25 publications

(56 reference statements)

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“…The therapeutic potential of curcumin has been reported in many diseases, including cancer and neurodegenerative disorders (Pluta et al, 2015; Panda et al, 2017). A growing number of reports suggest that curcumin can protect against stroke-induced brain damage (Thiyagarajan and Sharma, 2004; Lin et al, 2016; Miao et al, 2016; Altinay et al, 2017). In the present study, we reported that curcumin treatment not only ameliorated infarct volumes, but also improved multiple aspects of neurological function at early timepoints after ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies performed in stroke models have shown that curcumin exerts diverse neuroprotective functions, including antioxidative effects (Thiyagarajan and Sharma, 2004; Yang et al, 2009; Wu et al, 2013), regulation of neuronal (and other cell) apoptosis (Zhao et al, 2008, 2010; Altinay et al, 2017), promotion of mitochondrial biogenesis (Liu et al, 2014), and enhancement of neurogenesis (Liu S. et al, 2016). The present study demonstrates that curcumin reduces ischemic stroke-induced brain damage and improves several functional outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Curcumin has also been proposed as a promising agent for stroke prevention in humans (Ovbiagele, 2008). Manifold mechanisms are involved in the protective effects of curcumin, including anti-oxidative, anti-inflammatory (Thiyagarajan and Sharma, 2004; Yang et al, 2009; Wu et al, 2013), and anti-apoptotic mechanisms (Zhao et al, 2008, 2010; Altinay et al, 2017), as well as neurogenesis (Liu S. et al, 2016). However, the effect of curcumin on microglial phenotypic polarization after ischemic stroke has not been explored.…”

Section: Introductionmentioning

confidence: 99%

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Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization

Liu

Ran

Huang

et al. 2017

Front. Aging Neurosci.

136

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Stroke is the most common type of cerebrovascular disease and is a leading cause of disability and death. Ischemic stroke accounts for approximately 80% of all strokes. The remaining 20% of strokes are hemorrhagic in nature. To date, therapeutic options for acute ischemic stroke are very limited. Recent research suggests that shifting microglial phenotype from the pro-inflammatory M1 state toward the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. The dietary phytochemical curcumin has shown promise in experimental stroke models, but its effects on microglial polarization and long-term recovery after stroke are unknown. Here we address these gaps by subjecting mice to distal middle cerebral artery occlusion (dMCAO) and administering curcumin intraperitoneally (150 mg/kg) immediately after ischemia and 24 h later. Histological studies revealed that curcumin post-treatment significantly reduced cerebral ischemic damage 3 days after dMCAO. Sensorimotor functions—as measured by the adhesive removal test and modified Garcia scores—were superior in curcumin-treated mice at 3, 5, 7 and 10 days after stroke. RT-PCR measurements revealed an elevation of M2 microglia/macrophage phenotypic markers and a reduction in M1 markers in curcumin-treated brains 3 days after dMCAO. Immunofluorescent staining further showed that curcumin treatment significantly increased the number of CD206+Iba1+ M2 microglia/macrophages and reduced the number of CD16+Iba1+ M1 cells 10 days after stroke. In vitro studies using the BV2 microglial cell line confirmed that curcumin inhibited lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced M1 polarization. Curcumin treatment concentration-dependently reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-12p70, in the absence of any toxic effect on microglial cell survival. In conclusion, we demonstrate that curcumin has a profound regulatory effect on microglial responses, promoting M2 microglial polarization and inhibiting microglia-mediated pro-inflammatory responses. Curcumin post-treatment reduces ischemic stroke-induced brain damage and improves functional outcomes, providing new evidence that curcumin might be a promising therapeutic strategy for stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization

Liu

Ran

Huang

et al. 2017

Front. Aging Neurosci.

136

View full text Add to dashboard Cite

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“…The body temperature was monitored and maintained between 37.1˚C and 37.3˚C under free-regulating conditions with using a thermometer and heating pad during and after the surgery up to the animals recovered from anesthesia. After separation of the vagus nerve, bilateral common carotid arteries occlusion (two-vessel occlusion; 2-VO) was conducted by 20 min clamping [16,30,31]. After 20 min, clamps were removed for reperfusion onset either for 24 hours or for 7 days depends on different experimental sets.…”

Section: Surgical Procedures For Induction Global Cerebral I/r Modelmentioning

confidence: 99%

Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat

Moghadam

Fereidoni

2020

PLoS ONE

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Cerebral ischemia/reperfusion (I/R) injury causes cognitive deficits, excitotoxicity, neuroinflammation, oxidative stress and brain edema. Vitamin K2 (Menaquinone 4, MK-4) as a potent antioxidant can be a good candidate to ameliorate I/R consequences. This study focused on the neuroprotective effects of MK-4 for cerebral I/R insult in rat's hippocampus. The rat model of cerebral I/R was generated by transient bilateral common carotid artery occlusion for 20 min. Rats were divided into control, I/R, I/R+DMSO (solvent (1% v/ v)) and I/R+MK-4 treated (400 mg/kg, i.p.) groups. Twenty-four hours after I/R injury induction, total brain water content, superoxide dismutase (SOD) activity, nitrate/nitrite concentration and neuronal density were evaluated. In addition to quantify the apoptosis processes, TUNEL staining, as well as expression level of Bax and Bcl2, were assessed. To evaluate astrogliosis and induced neurotoxicity by I/R GFAP and GLT-1 mRNA expression level were quantified. Furthermore, pro-inflammatory cytokines including IL-1β, IL-6 and TNF-α were measured. Seven days post I/R, behavioral analysis to quantify cognitive function, as well as Nissl staining for surviving neuronal evaluation, were conducted. The findings indicated that administration of MK-4 following I/R injury improved anxiety-like behavior, short term and spatial learning and memory impairment induced by I/R. Also, MK-4 was able to diminish the increased total brain water content, apoptotic cell density, Bax/ Bcl2 ratio and GFAP mRNA expression following I/R. In addition, the high level of nitrate/nitrite, IL-6, IL-1β and TNF-α induced by I/R was reduced after MK-4 administration. However, MK-4 promotes the level of SOD activity and GLT-1 mRNA expression in I/R rat model. The findings demonstrated that MK-4 can rescue transient global cerebral I/R consequences via its anti-inflammatory and anti-oxidative stress features. MK-4 administration ameliorates neuroinflammation, neurotoxicity and neuronal cell death processes and leads to neuroprotection. PLOS ONEPLOS ONE | https://doi.org/10.1371/journal.pone.0229769 March 9, 2020 1 / 30 OPEN ACCESS Citation: Farhadi Moghadam B, Fereidoni M (2020) Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat. PLoS ONE 15(3): e0229769. https://

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“…Curcumin also reduced neuronal apoptosis by increasing the anti-apoptotic Bcl2 protein at the mitochondrial level, lowered cytosolic cytochrome c translocation [112,118] and decreased the mitochondrial membrane potential [121,125]. In addition, it causes reduced apoptosis [124][125][126] via caspase-3 mRNA downregulation [117,119] and stimulates neurogenesis [123] (Figure 1). Curcumin also reduces post-ischemic circulatory disturbances induced by neutrophils in animal stroke by preventing neutrophil adhesion to the brain microcirculation [114].…”

Section: Neuroprotection and Neurogenesismentioning

confidence: 98%

Substantiation for the Use of Curcumin during the Development of Neurodegeneration after Brain Ischemia

Ułamek-Kozioł

Czuczwar

Januszewski

et al. 2020

IJMS

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Currently available pharmacological treatment of post-ischemia-reperfusion brain injury has limited effectiveness. This review provides an assessment of the current state of neurodegeneration treatment due to ischemia-reperfusion brain injury and focuses on the role of curcumin in the diet. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of curcumin influence on post-ischemic brain damage. Some data on the clinical benefits of curcumin treatment of post-ischemic brain in terms of clinical symptoms and adverse reactions have been reviewed. The data in this review contributes to a better understanding of the potential benefits of curcumin in the treatment of neurodegenerative changes after ischemia and informs scientists, clinicians, and patients, as well as their families and caregivers about the possibilities of such treatment. Due to the pleotropic properties of curcumin, including anti-amyloid, anti-tau protein hyperphosphorylation, anti-inflammatory, anti-apoptotic, and neuroprotective action, as well as increasing neuronal lifespan and promoting neurogenesis, curcumin is a promising candidate for the treatment of post-ischemic neurodegeneration with misfolded proteins accumulation. In this way, it may gain interest as a potential therapy to prevent the development of neurodegenerative changes after cerebral ischemia. In addition, it is a safe substance and inexpensive, easily accessible, and can effectively penetrate the blood–brain barrier and neuronal membranes. In conclusion, the evidence available in a review of the literature on the therapeutic potential of curcumin provides helpful insight into the potential clinical utility of curcumin in the treatment of neurological neurodegenerative diseases with misfolded proteins. Therefore, curcumin may be a promising supplementary agent against development of neurodegeneration after brain ischemia in the future. Indeed, there is a rational scientific basis for the use of curcumin for the prophylaxis and treatment of post-ischemic neurodegeneration.

show abstract

Is chronic curcumin supplementation neuroprotective against ischemia for antioxidant activity, neurologic deficit score, or neuronal apoptosis in an experimental stroke model?

Abstract: We demonstrated the neuroprotective effect of chronic curcumin supplement on biochemical parameters, neurological scores and apoptosis following ischemia and reperfusion injury in rats.

Cited by 16 publications

References 25 publications

Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization

Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization

Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat

Substantiation for the Use of Curcumin during the Development of Neurodegeneration after Brain Ischemia

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