Suppressing Brain Immune Responses of Parkinson's Patients Gives Promising Therapeutic Approach - Parkinson's News Today

It happens that curcumin is a JAK/STAT inhibitor. The problem so far has been its poor absorption into the body and brain. Longvida optimized curcumin is 65x more bioavailable than standard curcumin and it achieves therapeutic levels in the brain. There's more info at longvida.com

I've been taking it for a while now but now I might increase my dose.

Related to this. I recall that this idea was discussed before on this forum.

Overactive Innate Immune System Seen as Underlying Cause of Neuronal Death in Parkinson's - Parkinson's News Today

The University of Alabama team, referenced by GerryW, report that:

"disruption of the JAK/STAT pathway using inhibitors commonly called Jakinibs, prevented the neuroinflammation and neurodegeneration seen in PD patients."

Given the difficulties of getting access to these drugs, it's worth seeing if there are natural alternatives, albeit probably weak. GerryW has reported that curcumin fits the bill. There are others.

Martin et al. report [1]:

"We have identified a range of food phytochemicals that inhibit Janus Kinase 2 (JAK2) and Adenosine Monophosphate Kinase (AMPK). A mutated and dysregulated form of JAK2, a tyrosine kinase, is associated with several diseases including Crohn's disease. ... Several fruits were potent inhibitors of JAK2: blackberry, boysenberry, feijoa, pomegranate, rosehip and strawberry, which all contain ellagitannins, known inhibitors of kinases. These fruits are in the Rosales and Myrtales plant orders. No other foods gave >1% of the maximal JAK2 inhibitory activities of these fruits."

References:

[1] Food Funct. 2015 Jan;6(1):305-12. doi: 10.1039/c4fo00626g. Epub 2014 Dec 2.
"JAK2 and AMP-kinase inhibition in vitro by food extracts, fractions and purified phytochemicals."
Martin H1, Burgess EJ, Smith WA, McGhie TK, Cooney JM, Lunken RC, de Guzman E, Trower T, Perry NB.
JAK2 and AMP-kinase inhibition in vitro by food extracts, fractions and purified phytochemicals. - PubMed - NCBI

John

I take Longvida curcumin and life extension's bio-enhanced version. I take two longvida and one life extension daily.

An interesting side note to this research is that Nilotinib (Tasigna) is a JAK/STAT inhibitor. Many of us are familiar with the results of the very successful trial last year with Nilotinib out of Georgetown. Of course it was very small and open label. Nevertheless, it's still encouraging to see supporting science elsewhere.

Interestingly, both curcumin and ellagic acid are reported to have an effect as MAO inhibitors. This puts them into the same ground as selegiline and rasagiline (Azilect). Working on rats, Khatri and Juvekar write [1] that 50% of MAO-B activity is inhibited by:
Curcumin 500.46nM
Ellagic acide 400.24
Selegine 65.5

Let's see where a very rough and ready analysis of the data takes us. The levodopa equivalent dose conversion factor for sublingual selegiline is 80 and for rasagiline it is 100 [2]. Given this, and assuming that the molecular weights and bio-availability are similar, this gives a curcumin conversion factor of 80*65.5/500.46, that is about 10. Given, also, that 1mg is a therapeutic dose of rasagiline, this suggests that 10mg is, for this pathway, a therapeutic dose of curcumin. Note, unfortunately, it is not additive beyond 1mg of rasagiline, because once all the MAO-B has been inhibited, there's nothing more to be gained by increasing the dose.

Reference:

[1] "Kinetics of inhibition of monoamine oxidase using curcumin and ellagic acid"
Dharmendra Kumar Khatri, Archana Ramesh Juvekar
Pharmacognosy Magazine, 11 May, 2016
Kinetics of inhibition of monoamine oxidase using curcumin and ellagic acid Khatri DK, Juvekar AR - Phcog Mag

[2] Parkinson's Disease Measurement: PwP, surveys, trials, analysis

John