In the advent of a stroke, turmeric can help because…

Turmerone Tackles Neurodegeneration
And provides benefits that cannot be obtained from curcumin

By Will Block

In March of 2015, Life Enhancement published an article about the amazing properties of ar-turmerone (turmerone)—see “Turmerone Induces Neural Stem Cell Proliferation”—an important compound found in whole turmeric (turmeric). These properties include:

• Self-repair and recovery of brain function

• Neural stem cell production

• Increase (up to 80%) of neural stem cells

• Subventricular zone widening and hippo­campus expansion

• Enhanced bioavailability of curcumin

All of these pertain to memory function, including the last item, on bioavailability. Consumption of turmeric (in curry) is associated with low levels of dementia. In a rural province of India, the residents show 4.4 times lower levels of Alzheimer’s disease than an equivalent populous in the U.S.1 That’s almost 1/5th the amount.

Furthermore, hundreds of studies show that curcumin and other bioactive compounds in turmeric are helpful for a wide array of memory problems, including protection against dementia in general, and Alzheimer’s disease in particular.

Both curcumin and turmerone are found in whole turmeric.

There are currently few offerings of turmerone as a supplement. If you buy it from Alibaba, expect to lay out many thousands of dollars for a minimum order. However, turmerone can be obtained from whole turmeric, along with all the curcuminoids, and many other health-bearing active constituents. And the price is affordable.

Stroke Recourse

Despite spending tremendous amounts of effort and money, there are few treatments available for those who have suffered brain injury as a consequence of a stroke.

Reparative mechanisms in the brain are often insufficient to address the damage caused by such an insult, and current therapeutic approaches, whether they are cell based, compound based, or a combination of the two, are too often inadequate to produce long-lasting benefits to the patient.

It is a formidable task to discover new avenues of treatment, especially given the many different challenges that need to be overcome to facilitate repair of the nervous system.

A paper authored by Hucklenbroich and colleagues presented in an issue of Stem Cell Research and Therapy provides evidence that turmerone, an extract from the herb Curcuma longa, could provide one of those avenues.2 This paper was cited in the aforementioned article “Turmerone Induces Neural Stem Cell Proliferation.”

Trophic Support for the Stroke Damaged Tissue

One aspect to address is providing trophic support to the damaged tissue, giving cells the opportunity to recover and return to normal function.3 Neural stem cells, activated as a consequence of injury, play a significant role in the regenerative process. This happens through their production of neurotrophic factors and cytokines such as brain-derived neurotrophic factor (BDNF) and Sonic hedgehog (Shh), instead of harnessing their ability to differentiate and physically replace damaged neurons, astrocytes, or oligodendrocytes. Shh is well known to play a key role in a variety of processes such as cell proliferation and protection, and tissue repair during inflammation.


Neural stem cells, activated as a
consequence of injury, play a
significant role in the
regenerative process.


Modulating the Inflammatory Process

Another issue to address is the excessive neuroinflammation associated with neurological damage. While initial inflammatory events provide important signals for attracting immune cells to deal with the acute damage as well as recruit neural stem cells, chronic inflammatory mediators produced through activated microglia oppose the recovery of damaged tissue through production of factors such as chemokines and free radicals.

Therefore, a valuable approach would be one that is multimodal in its cellular action, appropriately modulating the inflammatory process while activating endogenous neural stem cells, allows for the establishment of a regenerative microenvironment that facilitates innate repair and functional recovery.

Traditional herbal medicines are in the spotlight as the search for effective therapies continues. Some in particular are based upon extracts from a member of the Zingiberaceae family, Curcuma longa. It has long been used as part of traditional medicine for treating a broad spectrum of indications.

There are many investigations into the bioactive compounds it contains, with curcumin garnering most of the attention thus far, having multiple published reports demonstrating its effects on the survival of those with various cancer types as well as treating microbial infection, among other applications.

Despite its poor bioavailability, curcumin has far more studies than turmeric, for some reasons that likely depend on politics. It is interesting to emphasize that turmerone increases curcumin bioavailability. Durk & Sandy prefer turmeric for this and other reasons (see their article “Comparison of Efficacy of Turmeric and Curcumin in Immunological Measures and Gene Regulation,” in the February 2011 issue of Life Extension News, Volume 14 No. 1 in this publication).


Modulating the inflammatory process
while activating endogenous neural
stem cells, allows for the
establishment of a regenerative
microenvironment that facilitates
innate repair and functional recovery.


Treating Neuronal Damage

More recently, another component of turmeric, turmerone, has also moved into the spotlight as a potential therapy with appealing qualities for treating neuronal damage. Turmerone has documented anti-inflammatory properties, in particular towards the activity of microglia associated with neuroinflammation, meaning it satisfies the first criterion for that sought-after therapeutic approach.

Activate Endogenous Neural Stem Cells

What about the second criterion, the ability to activate endogenous neural stem cells? That piece of the puzzle is provided by the Hucklenbroich manuscript already cited, describing the effects of aromatic turmerone on fundamental neural stem cell properties.2 The authors of this paper demonstrate the interesting finding that, while treatment of fetal neural stem cells in vitro during expansion yields increased proliferation, treatment during differentiation promotes an increase in the number of generated neurons.

They utilize positron emission tomography imaging to show the effects of intra-cerebroventricular injection of turmerone on the mobilization of neural stem cells from both the subventricular zone and hippocampus.

This represents an important step in defining the beneficial cellular mechanism this class of compounds can exert on the regenerative process in the nervous system and opens an avenue for their therapeutic use. The fact that independent studies utilizing curcumin were published almost simultaneously with the findings of Hucklenbroich and colleagues showcases the therapeutic potential of this family of plants.


Turmerone increases curcumin
bioavailability.


The Mechanisms of Turmerone

Identifying the mechanism of action for turmerone will be key for it to move forward as a useful therapeutic. In the case of its anti-inflammatory effects, the details are coming to light, as turmerone inhibits NF-κB, JNK, and p38 activity in microglia.

However, how turmerone modulates the proliferation and differentiation of neural stem cells is not understood. One possibility is that it acts upon an emerging regulator of neural stem cell growth and survival. It is a distinct branch of the Notch signaling pathway activated by fibroblast growth factor 2, Delta4, angiopoietin 2, and insulin, all of which are able to increase neural stem cell number.

Treatment with these factors, especially in combination, results in the mobilization of endogenous neural stem cells and has powerful effects in recovery models of ischemic stroke and Parkinson’s disease.


Identifying the mechanism of action for
turmerone will be key for it to move
forward as a useful therapeutic.


Another Mechanism Worth Considering

Another way turmerone may work involves its suppression of STAT3 tyrosine 705 phosphorylation, a transcription factor that enables curcumin treatment in the context of cancer. If turmerone does the same in neural stem cells, it would operate as a JAK inhibitor does. Janus kinase inhibitors (JAK) are a type of medication or herbal medicine that functions by inhibiting the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway. These inhibitors have therapeutic application in the treatment of cancer and inflammatory diseases such as rheumatoid arthritis.

In one paper, curcumin has been fingered as a novel STAT3 pathway inhibitor for chemoprevention of lung cancer.4

Straightforward experiments could be performed to quickly assess the involvement of this mechanism of action. This would provide an important step forward in establishing therapeutic paradigms incorporating turmerone for providing benefit to those suffering from debilitating neurological conditions.

It would also bring turmerone to the foreground, ahead of curcumin is some important ways.

References

  1. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001;21:8370-7.
  2. Hucklenbroich J, Klein R, Neumaier B, Fink GR, Schroeter M, Rueger MA: Aromatic-tumerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther. 2014;5:100.
  3. Poser SW, Androutsellis-Theotokis A. Spicing up endogenous neural stem cells: aromatic-turmerone offers new possibilities for tackling neurodegeneration. Stem Cell Res Ther. 2014 Nov 17;5(6):127.
  4. Alexandrow MG, Song LJ, Altiok S, Gray J, Haura EB, Kumar NB. Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev. 2012 Sep;21(5):407-12.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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