Neuroprotective effects of Curcumin

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Neuroprotective effects of Curcumin

Postby NHE » Tue Dec 13, 2005 5:55 am

Here's a link to an interesting article regarding the neuroprotective effects of curcumin. Although this paper discusses the use of curcumin as a possible treatment for ischemic injury, the results likely cross over to MS. It would be interesting to discover if research has been done on a potential neuroprotective role of curcumin specifically in MS.

Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits.
J Neurosci Res. 2005 Oct 1;82(1):138-48.
Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.


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Postby LisaBee » Thu Dec 15, 2005 6:23 pm

I didn't see anything for curcumin and MS - but curcumin has been studied in experimental allergic encephalomyelitis EAE in mice. I

n an intraperitoneal administration, curcumin blocked EAE in mice (see abstract below).

An oral study showed a mild beneficial effect from curcumin in animal EAE (Verbeek et al (2005)). If you go to PubMed and look up this abstract, don't let the title scare you - it makes it sound like all flavenoids tested made the EAE worse but you have to read the whole abstract.

The problem with curcumin, and it explains the disparate results by route of administration (ip route versus oral route), is that curcumin is not readily orally absorbed. There is a company that has manufactured a supplement called bioperine (it is an extract of black pepper) and the company has some human data on how bioperine enhances curcumin bioavailability.

http://www.bioperine.com/

This web-posted data was published by Shoba et al. (1998) in Planta Med.

If you are interested, at this bioperine website go and click on the link "bioperine and curcumin" and it will show rat and human pharmacokinetic data.

This all suggests that curcumin is better absorbed with peppery spicy food, and there are supplements that have curcumin and bioperine together that can be bought over the web.


Here is one of the curcumin abstracts, the mice were administered curcumin intraperitoneally:

J Immunol
2002 Jun 15;168(12):6506-13. Related Articles, Links


Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes.

Natarajan C, Bright JJ.

Division of Neuroimmunology, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

Experimental allergic encephalomyelitis (EAE) is a CD4(+) Th1 cell-mediated inflammatory demyelinating autoimmune disease of the CNS that serves as an animal model for multiple sclerosis (MS). IL-12 is a proinflammatory cytokine that plays a crucial role in the induction of neural Ag-specific Th1 differentiation and pathogenesis of CNS demyelination in EAE and MS. Curcumin (1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally occurring polyphenolic phytochemical isolated from the rhizome of the medicinal plant Curcuma longa. It has profound anti-inflammatory activity and been traditionally used to treat inflammatory disorders. In this study we have examined the effect and mechanism of action of curcumin on the pathogenesis of CNS demyelination in EAE. In vivo treatment of SJL/J mice with curcumin significantly reduced the duration and clinical severity of active immunization and adoptive transfer EAE. Curcumin inhibited EAE in association with a decrease in IL-12 production from macrophage/microglial cells and differentiation of neural Ag-specific Th1 cells. In vitro treatment of activated T cells with curcumin inhibited IL-12-induced tyrosine phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT3 and STAT4 transcription factors. The inhibition of Janus kinase-STAT pathway by curcumin resulted in a decrease in IL-12-induced T cell proliferation and Th1 differentiation. These findings highlight the fact that curcumin inhibits EAE by blocking IL-12 signaling in T cells and suggest its use in the treatment of MS and other Th1 cell-mediated inflammatory diseases.

PMID: 12055272 [PubMed - indexed for MEDLINE]

^^^^^^^^

See also Aggarwal and Shishodia (2004) on EAE.

The tools are all there to do a study with MS patients. There is even a supplement to enhance oral absorption that has been studied in humans. I don't know if anyone has done anything more with it. Another research gem in the rough.

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Re: Neuroprotective effects of Curcumin

Postby NHE » Thu Dec 15, 2005 8:34 pm

Lisa wrote:I didn't see anything for curcumin and MS - but curcumin has been studied in experimental allergic encephalomyelitis EAE in mice.

Thanks Lisa. The link to the Bioperine website is helpful. The link to the EAE IL-12 paper is the same one that I posted to the IL-12 thread under the General Discussion topic. Great minds must think alike! :wink:

The tools are all there to do a study with MS patients. There is even a supplement to enhance oral absorption that has been studied in humans. I don't know if anyone has done anything more with it. Another research gem in the rough.

I think that it would be difficult to convince a pharmaceutical company to study turmeric (or its extract curcumin) in MS. There's little incentive since they can't patent turmeric. However, such a study would have a greater probability occurring at the Oregon Health Sciences University. They've had pretty good success studying Complementary Alternative treatments in MS, especially their work with another supplement, Lipoic Acid.

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Postby LisaBee » Fri Dec 16, 2005 10:20 am

Sorry to duplicate the abstract posting!

I agree, there is little incentive to research curcumin on the pharmaceutical side. I have seen some research on curcumin in cancer patients, though. I hope Oregon or some CAM organization will further the research.

As an aside, I recently saw on BBC's website where a group from India is posting a huge compendium of ancient Indian treatments for a variety of illnesses. This is in response to a push in other countries to patent some of these treatments, that is, to show that treatment was previous knowledge and therefore not patentable.


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Re: Neuroprotective effects of Curcumin

Postby NHE » Sat Dec 17, 2005 4:31 am

LisaBee wrote:Sorry to duplicate the abstract posting!

It's no big deal. It's great to see that I'm not alone in following this research and assessing its potential for treating MS. It was interesting to learn that the pharma companies are also looking at IL-12. Also of interest was to learn that one of the effects of Ifn-beta is to lower IL-12 levels.

I agree, there is little incentive to research curcumin on the pharmaceutical side.

It got me thinking though. Perhaps there's some way of conducting an eStudy or eSurvey at the very least?

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Postby Brownsfan » Sat Dec 17, 2005 10:48 am

Are turmeric and curcumin one in the same? Can tablet forms of tumeric be used? What dosage?

thanks
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Re: Neuroprotective effects of Curcumin

Postby NHE » Sat Dec 17, 2005 3:48 pm

Brownsfan wrote:Are turmeric and curcumin one in the same? Can tablet forms of tumeric be used? What dosage?

No, curcumin is a component of turmeric. It might be helpful to review my prior post in the IL-12 thread. Curcumin has also been found to be benificial for Alzheimer's Disease. I hope the discussions in those threads answer your questions though I would be happy to try to answer any more you might have.

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DHEA and IL 12 FYI

Postby Shayk » Sat Dec 17, 2005 9:03 pm

LisaBee and NHE—I really appreciate your informative posts and discussions. I really can’t participate in the discussions because I have absolutely no scientific background. Hormones are always lurking though. :)

NHE—given your interest in IL 12 I thought I’d mention that DHEA also inhibits IL 12.

Our data demonstrated that supraphysiologic levels of DHEA favored Th2 immune responses in vitro by inhibition of IL-12 production from APCs and/or stimulation of Th2 proliferation during the interactions of T cells with APCs.


Note that this was a supraphysiological level. If you've had your DHEA levels checked and they're low, it might be a hormone you'd at least want to have at a level that's normal for your age. From the sparse studies I've read, DHEA does seem to have a tendency to be low in people with MS (men and women).

Thanks again for sharing your expertise.

This one's OT, but I think Bromley, or anyone interested in viruses, may be interested. Antiviral Effect of DHEA on Japanese Encephalitis Viral Infection

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Postby CureOrBust » Wed Mar 15, 2006 4:39 am

hardly scientific, but i wasnt feeling so great last week, so i decided to up my curcumin dose. Normally i take 333mg x 2 (ie 666mg) curcumin a day. I upped this to 333mg x 6 (ie 999mg in three doses over the day) and I think It made a difference. When i first started it i didnt notice anything, i just take it as a backup.

I take a lot of other stuff, but this was the only thing i changed at the time. The curcumin suppliments I take also have bromelain (pineaple extract) & boperine (pepper fruit extract).

again not scientific, but it would be interesting to see if others notice a difference at this/a higher dose.
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Turmeric, Curcumin and IL-12

Postby notasperfectasyou » Thu Mar 16, 2006 11:39 am

I’ve seen a lot of posts about Turmeric and the entire topic is very interesting to me. Although I admit to being something of a supplement junkie, I do like to have a good idea about why I’m taking something and whether the basis for taking it is reasonable. So I’ve been working on a “layman’s” review of whatever information I could find about the stuff. So I’ll start out by saying, I’m an MS Fiancé and not a doctor. See your doctor for medical advice, yada, yada, yada.

The first thing I learned about Turmeric is that there’s another related substance called Curcumin. Here’s a link to the University of Maryland Medical Center’s Page on Turmeric. The site explains that curcumin is the active ingredient in turmeric. This webpage explains that the average amount of curcumin in turmeric is about 3% meaning, curcumin is considered to be the active ingredient in turmeric. There are a number of diseases that the National Institutes of Health have considered in review of turmeric and curcumin, however Multiple Sclerosis is not one of them. Rheumatoid arthritis, which is an autoimmune disease, is listed with the possibility that turmeric and curcumin might reduce inflammation.

Given all of this I wanted to first track down why anyone would be chasing down Curcumin for MS. I found the following publication on the Neurology Department at Vanderbilt website: “Natarajan, C., and Bright, John. J. 2002. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J. Immunol. 169, 6506-6513.” After some searching, I found the entire paper. This stuff is hard to read, it’s definitely worth the effort though. Here is a summarizing quote from the research:

”In this study, we have examined the effects and mechanism of action of curcumin on the pathogenesis of CNS inflammation and demyelination in EAE. Our results showed that curcumin inhibits CNS demyelination by blocking IL-12 production, IL-12 signaling, and differentiation of neural Ag-specific Th1 cells in EAE and suggest its use in the treatment of MS and other Th1 cell-mediated inflammatory diseases.”


There’s a lot of research out there on curcumin some of it tangentially related to MS topics. Here’s a site that has summarized info a number of research topics that have been explored in connection with curcumin. The flip side to all of this is that for scientific purposes curcumin’s benefit in EAE does not immediately mean that the same benefit exists for those with MS. It’s also not entirely clear that the blocking of IL-12 is the source of the benefit. In subsequent research that was published in 2003, IL-12 deficient mice were able to develop EAE.

” In summary, we report the unexpected finding of severe EAE in the absence of IL-12R 2. The mechanisms for this observation include increased production of proinflammatory molecules (such as TNF- , GM-CSF, IL-17, and NO), elevated IL-18/IL-18R interaction, and perhaps increased production of IL-23. The demonstration that the absence of IL-12R 2 can enhance the severity of EAE should further encourage the study of the IL-12/IL-23 system in experimental and human autoimmunity.”


Research still continues on IL-12, which suggests to me that it’s easy to observe the state at the beginning of a study and the state that the end of the study, while not knowing for sure what it was that actually happened. In 2005, IL-12 suppression is still being considered as a treatment for MS. IL-23 is “new” and related to IL-12. Here’s a quote from an abstract that might help put a current perspective this topic:

“Many inhibitors of NF- B and of IL-12 signal transduction have been proven effective in limiting or preventing disease in experimental autoimmune encephalomyelitis (EAE) models of MS. The sharing of the p40 subunit, the IL-12R 1 and components of the signal transduction pathways between IL-12 and IL-23 raises the question as to whether the beneficial effects of various drugs previously ascribed to inhibition of IL-12 may, in fact, have been due to concurrent blockage of both cytokines, or of IL-23, rather than IL-12.”


It seems to me that there must be some benefit, it’s just that no one has exactly pinpointed what it is so it can be reported to the world. One thing I have noticed while clicking my way through documents is a clear absence of anything that said not to take curcumin or that it is bad for you. The University of Maryland site (above) notes few side effects or warnings for curcumin, but nothing that tells me that it’s bad for the average person to take curcumin. The site also lists a recommended dosage of 400 to 600 mg, three times a day. I think there is little to lose and the potential for gain in taking this stuff.

In any case, I’m just one person with an opinion. Please reply to this post if you think I should add more information and/or links. Let me know what you think. napay

Other similar posts on my road to understanding MS:

Understanding MS 101: Doctor Talk and People Talk
A Layman’s Review of Glyconutrients – not good
Turmeric, Curcumin and IL-12 - good
C is for Controversy – good
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Curcumin, HPA and BDNF

Postby Shayk » Wed Mar 21, 2007 8:00 pm

NHE wrote:
It would be interesting to discover if research has been done on a potential neuroprotective role of curcumin specifically in MS

Brain-derived neurotrophic factor (BDNF) is something some MS researchers think might be beneficial to people with MS. This research isn't specific to MS but suggests curcumin might help offset the decrease in BDNF that is attributable to stress (aka HPA hyperactivity--cortisol)

Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB
We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction.

we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels

these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

It seems to me that since BDNF seems to be a good thing, this is at least very indirect research suggesting curcumin could potentially have a neuroprotective role in MS. 8)

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Postby dignan » Wed Mar 21, 2007 9:09 pm

Looks like a pharma company is taking a stab at tweaking curcumin and making it into a cancer treatment at least...



Curecumin(TM) May Be an Effective Treatment for Prostate Cancer

March 19 /PRNewswire-FirstCall/ -- Bioponic Phytoceuticals today
announced that its Curecumin (a Bioresonant Phytotherapeutic form of
Turmeric containing curcumin), may be an important treatment for prostate cancer.

"Curcumin, a turmeric root extract, has been shown to possess activity
in the treatment and prevention of cancer, multiple sclerosis, and
Alzheimer's disease," according to a 3/7/2007 article posted on UroToday.com.

"The molecular mechanism for its anticancer effect is largely unknown, although it is thought to inhibit the synthesis of MDM2, an oncoprotein known to bind p53 and modulate p21 expression. In the March 1 issue of Cancer Research, Li and colleagues from the Comprehensive Cancer Center of the University of Alabama report on a study designed to elucidate the molecular anticancer effect of curcumin in a preclinical prostate cancer model."

"Curcumin was found to decrease the mRNA and protein expression of the oncoprotein MDM2 and to enhance the expression of tumor modulator p21."

"This well-performed study provides an elegant mechanistic explanation for the anticancer effect of curcumin."

It is estimated by the Prostate Cancer Foundation that "prostate cancer
currently strikes an estimated one in six Americans. More than 218,000 menv in the United States will be diagnosed with prostate cancer this year."

"We are particularly interested in the potential of our Curecumin(TM)
product to provide a viable treatment strategy for those with prostate
cancer. If proven effective, we may have an efficacious, cost effective,
natural treatment for prostate cancer sufferers," said Steven M. Schorr,
Chairman & CEO -Bioponic Phytoceuticals, Inc.

Bioponic Phytoceuticals is engaged in the development, production and
distribution of Bioresonant Phytotherapeutic(TM) products for sale in the
Complementary Alternative Medicine ("CAM") and natural products markets.

Press release URL
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Cumin - 'dosage'

Postby Abe » Mon Jul 16, 2007 12:11 am

I think it is sensible to add Cumin to my regime.

What 'dose' would be theraputic. I will be taking it straight out of the spice jar so desert spoons are the measurement!

Would one slightly heaped desert spoonful per day be enough?

Thanks again, Abe
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Postby CureOrBust » Mon Jul 16, 2007 1:24 am

cumin or did you mean Tumeric?
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Postby syckbastid » Mon Jul 16, 2007 6:27 am

Curcumin is the ingredient that gives turmeric its orange color, and anti-inflammatory/neuro-protective properties.

I take Curcumin capsules (900mg 2x per day). Here's a link to a vitamin site where you can order:

<shortened url>

One day I'll learn that "tiny url" thing.
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