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Nathan Goodyear

Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acut... - 0 views

  • In a variety of solid tumors and blood cancers, aberrant hypermethylation of CpG-rich regions (>55% CG content, 0.5-4 kb in length, the so-called “CpG islands”) in the promoters of tumor suppressor genes (TSGs) results in their transcriptional silencing
  • These agents have been reported to suppress tumor growth by reversing aberrantly hypermethylation in the promoters of inactivated TSGs (e.g. p15INK4B), allowing re-expression of TSGs, thereby restoring normal cell cycle regulation, proliferation, apoptosis, and differentiation
  • groups have reported that curcumin acts as a scavenger of free radicals [13], an inhibitor of NF-κB nuclear translocation [14], and a modulator of histone deacetylase (HDAC) and histone acetyltransferase (HAT)
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  • In this study, we found that curcumin down-regulated DNMT1 expression in AML cells. This occurred, at least in part, through down-modulation of two positive regulators of DNMT1: Sp1 and the NF-κB component, p65. We also found that curcumin-mediated down-regulation of DNMT1 was associated with reactivation of TSGs and tumor suppression, both in vivo and in vitro.
  • curcumin may selectively downregulate DNMT1 expression in tumor cells, but not in normal cells
  • DNMT1 expression is positively regulated by Sp1 and the NF-κB signaling component
  • indicating that curcumin may have significant anti-tumor activity in AML
  • We found that, compared to the vehicle control, curcumin treatment reduced tumor weight by 70%
  • Surprisingly, although curcumin significantly inhibited tumor growth in these mice, we were unable to find any obvious toxicity associated with curcumin treatment
  • Consistent with our observations regarding curcumin’s ability to inhibit tumor growth in vivo (Figure 4) and down-regulate DNMT1 expression in vitro and ex vivo (Figure 1), we found that decreased levels of DNMT1 protein and mRNA were expressed by tumor cells isolated from curcumin-treated mice
  • we identified curcumin as a substance which acts as an inhibitor of DNA methyltransferase enzymatic activity and induces significant global DNA hypomethylation in AML cells
  • In this study, we first demonstrated that curcumin decreases DNMT1 mRNA and protein expression levels, most likely through inhibiting expression of positive regulators of DNMT1, such as Sp1 and the p65 component of NF-κB component, and/or altering their ability to bind to the promoter region of DNMT1
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    Curcumin beneficial in AML
Nathan Goodyear

Dietary Strategy to Repair Plasma Membrane After Brain Trauma - 0 views

  • strategies directed to preserve phospholipids in the plasma membrane such as the use of dietary docosahexaenoic acid (C22:6n-3; DHA)5 can have beneficial effects for post-TBI recovery
  • DHA is the most abundant polyunsaturated fatty acid (PUFA) in the brain
  • Curcumin provided in the diet before TBI can reduce oxidative damage and counteract TBI-related cognitive dysfunction.
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  • Our previous study indicated that n-3 fatty acids supplemented in the diet counteracted learning disability after TBI
  • There was a significant group effect on BDNF (F 4,25 = 5.229, P < .01 by ANOVA), and FPI reduced BDNF levels (50% of CTL, P < .01; Figure 1C), which was counteracted by DHA supplementation (90% of CTL, P < .05; Figure 1C). Curcumin also counteracted this reduction of BDNF
  • The combination of curcumin and DHA had a trend of greater effects in BDNF (117% of CTL; Figure 1C) compared with DHA or curcumin alone.
  • curcumin contributed to enhance the action of DHA, protecting against cognitive impairment, and these effects were associated with elevations in the BDNF receptor signaling
  • Our current results show that curcumin contributes to enhance the effects of DHA on TBI by promoting phosphorylation of the BDNF receptor TrkB in the hippocampus.
  • previous evidence indicates that curcumin10 and DHA5 counteract TBI-related learning disability by involving BDNF
  • The effects of the DHA diet and curcumin on cognitive enhancement were consistent with enhanced elevations in BDNF receptor signaling
  • effects of DHA and curcumin up to 2 weeks after TBI because this is the most critical period for the course of injury recovery because the brain is metabolically dysfunctional during this time
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    study that finds curcumin + DHA increased cognitive improvement after TBI within 2 weeks.  Good discussion of the proposed mechanism--increased BDNF.
Nathan Goodyear

Dietary Strategy to Repair Plasma Membrane After Brain Trauma - 0 views

  • concussive brain injury is a major cause of neuropsychological disability in spite of no obvious neuronal death
  • TBI elicits oxidative damage to plasma membrane phospholipids
  • DHA is the most abundant polyunsaturated fatty acid (PUFA) in the brain, where the DHA-containing phospholipids contribute to plasma membrane biogenesis and receptor signaling
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  • curcumin has potent anti-inflammatory and antioxidant activities that can function to reduce oxidative damage and cognitive deficits associated with neurological disorders
  • Curcumin provided in the diet before TBI can reduce oxidative damage and counteract TBI-related cognitive dysfunction
  • Our previous study indicated that n-3 fatty acids supplemented in the diet counteracted learning disability after TBI
  • curcumin contributes to enhance the effects of DHA on TBI by promoting phosphorylation of the BDNF receptor TrkB in the hippocampus
  • previous evidence indicates that curcumin10 and DHA5 counteract TBI-related learning disability by involving BDNF
  • Our findings indicate that curcumin counteracted the TBI-related reduction in n-3 DPA.
  • curcumin may promote the conversion of n-3 DPA to DHA
  • the combination of both nutrients has been reported to produce anti-inflammatory action
  • the enhanced actions of curcumin and DHA in reducing cholesterol levels could be interpreted as preservation of levels of phospholipids in the plasma membrane
  • curcumin and DHA may contribute to reduce inflammation associated with the action of cholesterol in the pathology of TBI.
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    Curcumin and DHA shown to protect against TBI through a reduction in inflammation and maintenance of brain phospholipid membranes.  BDNF is increases also.
Nathan Goodyear

Curcumin reverses impaired cognition and n... [Neuropharmacology. 2009] - PubMed - NCBI - 0 views

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    curcumin shown to improve and reverse memory disturbances in those with stress induced hippocampal neurodamage.  Curcumin was also shown to improve learning.  Additionally, curcumin was shown to be neuroprotective.  
Nathan Goodyear

Curcumin-induced suppression of adipogenic differentiation is accompanied by ... - 0 views

  • Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity-associated inflammation and diabetes in obese mice.
  • Curcumin also suppresses adipocyte differentiation
  • curcumin-induced suppression of adipogenesis
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    Curcumin reduces inflammation associated with obesity and Diabetes
Nathan Goodyear

Curcumin Inhibits Adipogenesis in 3T3-L1 Adipocytes and Angiogenesis and Obesity in C57... - 0 views

  • Dietary polyphenols may suppress growth of adipose tissue through their antiangiogenic activity and by modulating adipocyte metabolism
  • curcumin, the major polyphenol in turmeric spice
  • curcumin suppression of angiogenesis in adipose tissue together with its effect on lipid metabolism in adipocytes may contribute to lower body fat and body weight gain
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  • Our findings suggest that dietary curcumin may have a potential benefit in preventing obesity
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    Curcumin useful in obesity
Nathan Goodyear

Stuck at the bench: Potential natural neuroprotective compounds for concussion - 0 views

  • Long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are highly enriched in neuronal synaptosomal plasma membranes and vesicles
  • The predominant CNS polyunsaturated fatty acid is DHA
  • effective supplementation and/or increased ingestion of dietary sources rich in EPA and DHA, such as cold-water fish species and fish oil, may help improve a multitude of neuronal functions, including long-term potentiation and cognition.
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  • multiple preclinical studies have suggested that DHA and/or EPA supplementation may have potential benefit through a multitude of diverse, but complementary mechanisms
  • pre-injury dietary supplementation with fish oil effectively reduces post-traumatic elevations in protein oxidation
  • The benefits of pre-traumatic DHA supplementation have not only been independently confirmed,[150] but DHA supplementation has been shown to significantly reduce the number of swollen, disconnected and injured axons when administered following traumatic brain injury.
  • DHA has provided neuroprotection in experimental models of both focal and diffuse traumatic brain injury
  • potential mechanisms of neuroprotection, in addition to DHA and EPA's well-established anti-oxidant and anti-inflammatory properties
  • Despite abundant laboratory evidence supporting its neuroprotective effects in experimental models, the role of dietary DHA and/or EPA supplementation in human neurological diseases remains uncertain
  • Several population-based, observational studies have suggested that increased dietary fish and/or omega-3 polyunsaturated fatty acid consumption may reduce risk for ischemic stroke in several populations
  • Randomized control trials have also demonstrated significant reductions in ischemic stroke recurrence,[217] relative risk for ischemic stroke,[2] and reduced incidence of both symptomatic vasospasm and mortality following subarachnoid hemorrhage
  • Clinical trials in Alzheimer's disease have also been largely ineffective
  • The clinical evidence thus far appears equivocal
  • curcumin has gained much attention from Western researchers for its potential therapeutic benefits in large part due to its potent anti-oxidant[128,194,236] and anti-inflammatory properties
  • Curcumin is highly lipophilic and crosses the blood-brain barrier enabling it to exert a multitude of different established neuroprotective effects
  • in the context of TBI, a series of preclinical studies have suggested that pre-traumatic and post-traumatic curcumin supplementation may bolster the brain's resilience to injury and serve as a valuable therapeutic option
  • Curcumin may confer significant neuroprotection because of its ability to act on multiple deleterious post-traumatic, molecular cascades
  • studies demonstrated that both pre- and post-traumatic curcumin administration resulted in a significant reduction of neuroinflammation via inhibition of the pro-inflammatory molecules interleukin 1β and nuclear factor kappa B (NFκB)
  • no human studies have been conducted with respect to the effects of curcumin administration on the treatment of TBI, subarachnoid or intracranial hemorrhage, epilepsy or stroke
  • studies have demonstrated that resveratrol treatment reduces brain edema and lesion volume, as well as improves neurobehavioral functional performance following TBI
  • green tea consumption or supplementation with its derivatives may bolster cognitive function acutely and may slow cognitive decline
  • At least one population based study, though, did demonstrate that increased green tea consumption was associated with a reduced risk for Parkinson's disease independent of total caffeine intake
  • a randomized, placebo-controlled trial demonstrated that administration of green tea extract and L-theanine, over 16 weeks of treatment, improved indices of memory and brain theta wave activity on electroencephalography, suggesting greater cognitive alertness
  • Other animal studies have also demonstrated that theanine, another important component of green tea extract, exerts a multitude of neuroprotective benefits in experimental models of ischemic stroke,[63,97] Alzheimer's disease,[109] and Parkinson's disease
  • Theanine, like EGCG, contains multiple mechanisms of neuroprotective action including protection from excitotoxic injury[97] and inhibition of inflammation
  • potent anti-oxidant EGCG which is capable of crossing the blood-nerve and blood-brain barrier,
  • Epigallocatechin-3-gallate also displays neuroprotective properties
  • More recent research has suggested that vitamin D supplementation and the prevention of vitamin D deficiency may serve valuable roles in the treatment of TBI and may represents an important and necessary neuroprotective adjuvant for post-TBI progesterone therapy
  • Progesterone is one of the few agents to demonstrate significant reductions in mortality following TBI in human patients in preliminary trials
  • in vitro and in vivo studies have suggested that vitamin D supplementation with progesterone administration may significantly enhance neuroprotection
  • Vitamin D deficiency may increase inflammatory damage and behavioral impairment following experimental injury and attenuate the protective effects of post-traumatic progesterone treatment.[37]
  • emerging evidence has suggested that daily intravenous administration of vitamin E following TBI significantly decreases mortality and improves patient outcomes
  • high dose vitamin C administration following injury stabilized or reduced peri-lesional edema and infarction in the majority of patients receiving post-injury treatment
  • it has been speculated that combined vitamin C and E therapy may potentiate CNS anti-oxidation and act synergistically with regards to neuroprotection
  • one prospective human study has found that combined intake of vitamin C and E displays significant treatment interaction and reduces the risk of stroke
  • Pycnogenol has demonstrated the ability to slow or reduce the pathological processes associated with Alzheimer's disease
  • Pcynogenol administration, in a clinical study of elderly patients, led to improved cognition and reductions in markers of lipid peroxidase
  • One other point of consideration is that in neurodegenerative disease states like Alzheimer's disease and Parkinson's disease, where there are high levels of reactive oxygen species generation, vitamin E can tend to become oxidized itself. For maximal effectiveness and to maintain its anti-oxidant capacity, vitamin E must be given in conjunction with other anti-oxidants like vitamin C or flavonoids
  • These various factors might account for the null effects of alpha-tocopherol supplementation in patients with MCI and Alzheimer's disease
  • preliminary results obtained in a pediatric population have suggested that post-traumatic oral creatine administration (0.4 g/kg) given within four hours of traumatic brain injury and then daily thereafter, may improve both acute and long-term outcomes
  • Acutely, post-traumatic creatine administration seemed to reduce duration of post-traumatic amnesia, length of time spent in the intensive care unit, and duration of intubation
  • At three and six months post-injury, subjects in the creatine treatment group demonstrated improvement on indices of self care, communication abilities, locomotion, sociability, personality or behavior and cognitive function when compared to untreated controls
  • patients in the creatine-treatment group were less likely to experience headaches, dizziness and fatigue over six months of follow-up
  • CNS creatine is derived from both its local biosynthesis from the essential amino acids methionine, glycine and arginine
  • Studies of patients with CNS creatine deficiency and/or murine models with genetic ablation of creatine kinase have consistently demonstrated significant neurological impairment in the absence of proper creatine, phosphocreatine, or creatine kinase function; thus highlighting its functional importance
  • chronic dosing may partially reverse neurological impairments in human CNS creatine deficiency syndromes
  • Several studies have suggested that creatine supplementation may also reduce oxidative DNA damage and brain glutamate levels in Huntington disease patients
  • Another study highlighted that creatine supplementation marginally improved indices of mood and reduced the need for increased dopaminergic therapy in patients with Parkinson's disease
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    great review of natural therapies in the treatment of concussions
Nathan Goodyear

Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurode... - 0 views

  • The starting dose was 500 mg/day and if no toxicity was noted, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. There was no treatment-related toxicity up to 8 g/day but the bulky volume of the drug was unacceptable to the patients beyond 8 g/day.
  • The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of curcumin and gradually declined within 12 hours
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    Great article on the benefits of curcumin in therapy for inflammation and disease.
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Nathan Goodyear

Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice sugg... - 0 views

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    curcumin shown to inhibit NF-kappaB through a IL-10 dependent pathway.  IL-10 is required and curcumin appears to augment the inhibition of NF-kappaB
Nathan Goodyear

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer... - 0 views

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    Curcumin downregulates HER-2 oncoprotein in breast cancer in vitro and in vivo.  IN this study, the combination of taxol and curcumin was comparable to that of taxol and perceptin.
Nathan Goodyear

Efficacy of liposomal curcumin in a human pan... [Anticancer Res. 2013] - PubMed - NCBI - 0 views

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    liposomal curcumin at 20 mg/kg reduced pancreatic tumor growth by 42% in in vitro and xenograft studies.  The curcumin, the most prevalent polyphenol in tumeric, was given intraperitoneal in this study.
Nathan Goodyear

Efficacy and Safety of Curcumin in Major Depre... [Phytother Res. 2013] - PubMed - NCBI - 0 views

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    Study finds that curcumin alone is better than Prozac for Major depression.  Though not statistically significant, the response rate as determined by the Hamilton Depression scale favored curcumin above that of Prozac.  The effective dose was 1000 mg in this study.  The combination also provided additional benefit above that of prozac alone.
Nathan Goodyear

Dietary curcumin counteracts the outcome of traum... [Exp Neurol. 2006] - PubMed - NCBI - 0 views

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    curcumin functions to reduce inflammation and free radicals.  Curcumin also increases BDNF post TBI, which will improve synaptic plasticity, cognition, and memory.  
Nathan Goodyear

PLOS ONE: Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for T... - 0 views

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    Not only is curcumin beneficial in neuroprotection, but curcumin can aid neuroplasticity as shown in this rat model.
Nathan Goodyear

JN | Full text | Polymeric nanoparticle-encapsulated curcumin (nanocurcumin): a novel s... - 0 views

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    nano-encapsulated curcumin found to be as effective as free curcumin in inhibition of NF-kappaB.  This study looked at pancreatic cell lines.
Nathan Goodyear

Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice wi... - 0 views

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    Just abstract available here.  Curcumin reduces NF-kappaB, Cox2 and 5 lipoxygenase and the cytokines TNF-alpha and IL-1 and IL-6.  This implicates curcumin as an adjuvant for all chronic diseases of aging that involve inflammation.
Nathan Goodyear

Chemotherapeutic potential of curcumin for colorectal cancer. - PubMed - NCBI - 0 views

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    Only abstract available here.  Good discussion of the effects of curcumin: curcumin inhibits carcinogenesis, increases glutathione production, inhibits promotion and progression (mets) of cancer, induces cell apoptosis (cell death).
Nathan Goodyear

Curcumin Attenuation of Lipopolysaccharide Induced Cardiac Hypertrophy in Rodents - 0 views

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    This is just to cool. Curcumin found to inhibit LPS mediated cardiac hypertrophy. The how is fascinating. No only does LPS induce inflammatory cytokine production, but he inflammation induces disease--cardiac hypertrophy. LPS induces epigenetic changes that lead to the hypertrophy. Curcumin blocked the histone acetylation induced by LPS.
Nathan Goodyear

Curcumin interrupts the interaction between the androgen receptor and Wnt/β-c... - 0 views

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    Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced suppression of β-catenin
Nathan Goodyear

Curcumin attenuates the development of allergic airway inflammation and hyper-responsiv... - 0 views

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    curcumin shown to inhibit allergic airway inflammation, through NF-kappaB inhibition.  This has implications in asthma flares.
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