94 replies to this topic

[NZT48_User]

"The authors discovered that mice lacking PKR in the brain have a kind of "super" memory."

http://www.scienceda...11208125716.htm

"through a test in which mice use visual cues for finding a hidden platform in a circular pool, they found that normal mice had to repeat the task multiple times over many days in order to remember the platform's location. By contrast, mice lacking PKR learned the task after only one training session."

There have been few drugs discovered that inhibit PKR(such as C16 or PKRi), but it's too expensive for common people, so I searched for possible inhibitors of PKR that come from herbs.
Here's what I've found:

A substance called Shikonin can inhibit the PKR pathway

http://www.ncbi.nlm....pubmed/17360831

"our findings suggest that shikonin may achieve differential modulation of cytokine protein expression through inactivation of the PKR pathway"

Shikonin comes from an herb called Zi Cao (Purple Gromwell)

So, does this mean that Zi Cao can be considered a nootropic? Is this herb potent enough for cognitive enhancement? Are super doses necessary for an effect? And if so, what are the side effects?

I've been taking small amounts of Zi Cao, which I ordered from amazon. But I don't notice any effect. I'm not comfortable with taking super doses, since there are a ton of different chemicals in one herb. Maybe there's some way to extract the shikonin? That might be a little out of my league though.

Please leave serious responses. I'm not interested in cheesy comments or jokes.

[Turnbuckle]

At present, screening for anticancer shikonin derivatives is based on cellular level to find compounds with stronger cytotoxicity. Though several compounds have been discovered with striking cytotoxicity in vitro, however, no selectivity was observed and undoubtedly, the further outcomes have been disappointing because of their great damage to normal cells.

http://www.ncbi.nlm....pubmed/22834677

[NZT48_User]

At present, screening for anticancer shikonin derivatives is based on cellular level to find compounds with stronger cytotoxicity. Though several compounds have been discovered with striking cytotoxicity in vitro, however, no selectivity was observed and undoubtedly, the further outcomes have been disappointing because of their great damage to normal cells.

http://www.ncbi.nlm....pubmed/22834677

So, it looks like this article is describing the search for shikonin derivatives, particularly derivatives that have stronger cytotoxicity on cancer cells without harming normal cells. It's an interesting article, but is it even relevant to shikonin itself?

[NZT48_User]

They say that PKR inhibitors work by inhibition of the cytokine Interferon-gamma(IFN-gamma). Inhibiting IFN-gamma inhibits GABA, therefore strengthening the memory encoding process.

But I have a theory that describes a more complex set of mechanisms:
PKR inhibitor turns off IFN-gamma ---> this up-regulates Chondroitin Sulfate Proteoglycan(CSPG) ---> CSPG up-regulates Rho-Associated Protein Kinase(ROCK) ---> ROCK increases the activity of the motor protein Myosin II ---> up-regulation of Myosin II is what makes the memory enhancement possible.

http://www.scripps.e...0/rumbaugh.html

Any biochemists here who can comment on this?

Edited by NZT48_User, 12 December 2012 - 11:19 PM.

[lordbaal1009]

How much did you take? I'm willing to mega dose it - Tbh not really afraid of any possible side effects, because I doubt it has any ( I know, ignorance)

[stablemind]

I hope someone here will be ballsy enough to synthesize this and feed it to some rats in an experiment.

[NZT48_User]

I ordered from here:
http://www.amazon.co...keywords=zi cao

The product description says "1 bottle of 100g of concentrated herbs taken from 500g of raw herbs", but I think I'd rather have the unaltered Zi Cao next time.

I don't really measure. Something like 2 big capsules at one sitting.

They've already tested PKR inhibitors on rats. I would say the next step is humans testing and safety establishment, which is very expensive and time consuming.

[stablemind]

I ordered from here:
http://www.amazon.co...keywords=zi cao

The product description says "1 bottle of 100g of concentrated herbs taken from 500g of raw herbs", but I think I'd rather have the unaltered Zi Cao next time.

I don't really measure. Something like 2 big capsules at one sitting.

They've already tested PKR inhibitors on rats. I would say the next step is humans testing and safety establishment, which is very expensive and time consuming.

I just thought it would be a good idea to replicate this experiment first just like how people are already replicating the buckyballs experiment on rats. But since you're gonna be the guinea pig, I'm pretty excited to hear the results.

[lordbaal1009]

I've only read positive things about Zi Cao - I am willing to work my way up to a big dose. It sounds like you are taking 3-4 grams NZT48; I might try up to 20 grams a day. I wonder how long it takes for the effects to take place though? Considering how expensive it is running it at those doses.

[NZT48_User]

I just weighed 2 full capsules of the Zi Cao. It was 1.37 grams(including the capsules weight). What are Buckyballs?

[samiamm]

wait....what?

So did you happen to search what else PKR inhibition does to you??

[NZT48_User]

wait....what?

So did you happen to search what else PKR inhibition does to you??

Why? Have there been side effects?

[NZT48_User]

IFN-gamma is a cytokine, which functions as part as the immune system. So, theoretically, PKR inhibitors can weaken the immune system. But researchers concluded in studies that when IFN-gamma is inhibited, other cytokines will take it's place.

[samiamm]

Idk of any myself, i'm just asking you. After all, this is only a theory from you, but interestingly enough, I found this.


http://www.ncbi.nlm....pubmed/19046382


I actually found that by searching "PKR INHIBITION"

I can't find anything, but honestly, I haven't been looking extensively.

[NZT48_User]

The link between PKR inhibition and memory is not a theory. I'm only theorizing it's possible mechanisms.

http://www.huffingto..._n_1158330.html

[Daryl]

How about this:

http://www.scbt.com/...-inhibitor.html

"PKR Inhibitor is an imidazolo-oxindole derivative that has been shown to inhibit RNA-induced PKR autophosphorylation and rescue PKR-dependent translation block"

Looks stupid pricey though, but at least dosing high amount of this as opposed to Zi Cao would avoid concurrent high doses of whatever else is in Zi Cao(?)

[NZT48_User]

If it costs an arm and a leg, it doesn't interest me in the slightest. I think most people would agree with me.

You know...Just thinking a little off topic. Even if a drug like NZT was found, it wouldn't be used to attain wealth and power(Such as what was depicted in the movie "Limitless"). That's an errand for a weaker mind. So just to those who believe that someday they're gonna be a rich and powerful genius...your a little off.

In strong sense, being a genius is a burden, not a gift.

Edited by NZT48_User, 13 December 2012 - 03:49 AM.

[NZT48_User]

I've only read positive things about Zi Cao - I am willing to work my way up to a big dose. It sounds like you are taking 3-4 grams NZT48; I might try up to 20 grams a day. I wonder how long it takes for the effects to take place though? Considering how expensive it is running it at those doses.

I would increase the dose slowly. There's really no rush.

For anyone who wants to be smart. Step 1: Don't be ignorant. Be patient.

[stablemind]

I just weighed 2 full capsules of the Zi Cao. It was 1.37 grams(including the capsules weight). What are Buckyballs?

http://extremelongev...span-extension/

[NZT48_User]

I just weighed 2 full capsules of the Zi Cao. It was 1.37 grams(including the capsules weight). What are Buckyballs?

http://extremelongev...span-extension/

Interesting. I won't be touching that stuff any time soon. But still interesting.

[stablemind]

How about this:

http://www.scbt.com/...-inhibitor.html

"PKR Inhibitor is an imidazolo-oxindole derivative that has been shown to inhibit RNA-induced PKR autophosphorylation and rescue PKR-dependent translation block"

Looks stupid pricey though, but at least dosing high amount of this as opposed to Zi Cao would avoid concurrent high doses of whatever else is in Zi Cao(?)

I think I have a friend that works there. This place is in my area.

[lordbaal1009]

How about this:

http://www.scbt.com/...-inhibitor.html

"PKR Inhibitor is an imidazolo-oxindole derivative that has been shown to inhibit RNA-induced PKR autophosphorylation and rescue PKR-dependent translation block"

Looks stupid pricey though, but at least dosing high amount of this as opposed to Zi Cao would avoid concurrent high doses of whatever else is in Zi Cao(?)

What kind of dosage would we use?

[LBGSHI]

They say that PKR inhibitors work by inhibition of the cytokine Interferon-gamma(IFN-gamma). Inhibiting IFN-gamma inhibits GABA, therefore strengthening the memory encoding process.

Inhibiting GABA isn't necessarily a good idea. Take a look at the functions of GABA - http://en.wikipedia.org/wiki/GABA

Here is a quick list of some GABA inhibitors - http://en.wikipedia....GABA_antagonist

That being said, it's a very interesting experiment, and I'm all for it...I just won't be engaging in it

Edited by LBGSHI, 13 December 2012 - 04:50 PM.

[NZT48_User]

You always give the most informative posts, LBGSHI. I agree 100%. If PKR inhibitor worked by being a GABA inhibitor, there would be side effects across the board. Ex: Bicuculline, a GABA antagonist, can mimic epilepsy. But apparently, no side effects have been found with the PKR inhibitor in rats. That's why I've proposed a new set of mechanisms. I think it works through strengthening Myosin II. Down-regulation of GABA must be an indirect effect. I say it's probably a very specific inhibition on GABA(not the same as a full-on GABA antagonist).

[samiamm]

You always give the most informative posts, LBGSHI. I agree 100%. If PKR inhibitor worked by being a GABA inhibitor, there would be side effects across the board. Ex: Bicuculline, a GABA antagonist, can mimic epilepsy. But apparently, no side effects have been found with the PKR inhibitor in rats. That's why I've proposed a new set of mechanisms. I think it works through strengthening Myosin II. Down-regulation of GABA must be an indirect effect. I say it's probably a very specific inhibition on GABA(not the same as a full-on GABA antagonist).

....yeah, you know, stuff like this is what I was talking about. lmao

[NZT48_User]

You always give the most informative posts, LBGSHI. I agree 100%. If PKR inhibitor worked by being a GABA inhibitor, there would be side effects across the board. Ex: Bicuculline, a GABA antagonist, can mimic epilepsy. But apparently, no side effects have been found with the PKR inhibitor in rats. That's why I've proposed a new set of mechanisms. I think it works through strengthening Myosin II. Down-regulation of GABA must be an indirect effect. I say it's probably a very specific inhibition on GABA(not the same as a full-on GABA antagonist).

....yeah, you know, stuff like this is what I was talking about. lmao

If I can't use my brain to create new ideas, I don't know why I have one. I'm not a zombie who follows the crowd. I also take my own thoughts as pure gold. lol

[LBGSHI]

You always give the most informative posts, LBGSHI. I agree 100%. If PKR inhibitor worked by being a GABA inhibitor, there would be side effects across the board. Ex: Bicuculline, a GABA antagonist, can mimic epilepsy. But apparently, no side effects have been found with the PKR inhibitor in rats. That's why I've proposed a new set of mechanisms. I think it works through strengthening Myosin II. Down-regulation of GABA must be an indirect effect. I say it's probably a very specific inhibition on GABA(not the same as a full-on GABA antagonist).

That could very well be the case. GABA antagonists can act on specific areas of the brain, or even specific mechanisms (and proportions) of GABA.

[stablemind]

You always give the most informative posts, LBGSHI. I agree 100%. If PKR inhibitor worked by being a GABA inhibitor, there would be side effects across the board. Ex: Bicuculline, a GABA antagonist, can mimic epilepsy. But apparently, no side effects have been found with the PKR inhibitor in rats. That's why I've proposed a new set of mechanisms. I think it works through strengthening Myosin II. Down-regulation of GABA must be an indirect effect. I say it's probably a very specific inhibition on GABA(not the same as a full-on GABA antagonist).

....yeah, you know, stuff like this is what I was talking about. lmao

If I can't use my brain to create new ideas, I don't know why I have one. I'm not a zombie who follows the crowd. I also take my own thoughts as pure gold. lol

Since you're in Houston, maybe you would want to get in touch with one of the researchers directly and find out more info like the dose they used on the study. They are at Bayor College of Medicine.

http://www.cell.com/...092867411013754

[lifebuddy]

is there a reason why we don't remember everything at a glance? we have experience filters that allow us to live reasonable lives instead of being distracted by every stimulation and sensory twitch. eg. try tripping hard on acid every day for months. it gets easier after a while but it is hard to concentrate on every day activities when you are noticing too much.

[stablemind]

is there a reason why we don't remember everything at a glance? we have experience filters that allow us to live reasonable lives instead of being distracted by every stimulation and sensory twitch. eg. try tripping hard on acid every day for months. it gets easier after a while but it is hard to concentrate on every day activities when you are noticing too much.

Our minds have evolved to understand and apply abstract ideas and theories to increase our chances of survival. I think that over time we needed route memory less and less since our environment is so dynamic and we can't do the same things over and over. We need to make predictions and apply abstract thinking. There are actually savants like Kim Peak or Daniel Tammet who have super memories but those are few and far between. Kim Peak is an example of a savant with a memory of a super computer, however his ability to manipulate and solve abstract problems is very limited. His IQ is about equal to a five year old's.