94 replies to this topic

[renfr]

So what your doing you recommend not doing?
Anyways if anyone is avid about obtaining this chemical you can synthesize it in 6 steps http://www.sciencedi...04040391200857X

Or take 10g max of Zi Cao but overdose is from liver problems. Also its not recommended to be consumed anymore. Perhaps additional compounds are bad for the body. Any other plants contain this compound?

Why would you synthetize it? Unless you have a lab at home but I don't think most people in this forum do.
There's a vendor on Alibaba who sells as low as 20mg of shikonin : http://www.alibaba.c...7_89_5.html?s=p
But that's kinda risky, we do know how much Zi Cao to take but not how much shikonin to take.

If there is gaba downregulation then it must be a gaba agonist. The reason people would take a gaba antagonist is to improve thier mempory forthe long term. Is this herb able to be ethanol extracted?

Where did you read it is an agonist at GABA receptors?

Edited by renfr, 20 December 2012 - 06:38 AM.

[NZT48_User]

If there is gaba downregulation then it must be a gaba agonist.

Where did you read it is an agonist at GABA receptors?

Faulty logic and half listening.

[stablemind]

I asked a bunch of the researchers the questions but only one responded. When asked about the dosage given to the mice, he responded:

The mice were given 0.1 mg/kg i.p.

The research, he said, is still going on but human trials will be a while from now.

Anyone wanna replicate this on their own mice?

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

Edited by stablemind, 30 December 2012 - 07:23 AM.

[kevinseven11]

If gaba receptors down regulate there are only a few reasons why this could happen and we assume this isn't toxic to the cell. An agonist is the only way I can think of, please explain how else.

[renfr]

If gaba receptors down regulate there are only a few reasons why this could happen and we assume this isn't toxic to the cell. An agonist is the only way I can think of, please explain how else.

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.

It doesn't downregulate GABA, theorically it should rather upregulate GABA receptors.
Through a complex mechanism, it inhibits GABA production but doesn't mean the receptors are blocked, it works rather with a compensatory mechanism.

By the way, I just received my bottle of Mayway Zi Cao, I don't think I will try it today, probably tomorrow.

[kevinseven11]

Yeah I must of read just one post that sounded like you guys were saying it was an agonist. Im sorry.
If you guys plan on testing out this chemical be sure to dissolve it in a solvent (ethanol) or else you will get some bad absorption. This study explains. http://www.ncbi.nlm....pubmed/22998586
Taking NAC will help prevent cytotoxicity. http://www.ncbi.nlm....pubmed/22005156
Very interesting chemical!

[renfr]

Yeah I must of read just one post that sounded like you guys were saying it was an agonist. Im sorry.
If you guys plan on testing out this chemical be sure to dissolve it in a solvent (ethanol) or else you will get some bad absorption. This study explains. http://www.ncbi.nlm....pubmed/22998586
Taking NAC will help prevent cytotoxicity. http://www.ncbi.nlm....pubmed/22005156
Very interesting chemical!

Why ethanol? The study says it's put in oil based preparations but not ethanol.
Beta lactoglobulin is found in milk, that's a good thing.
I wonder if NZT48 swallowed it with some milk?
Btw happy new year everyone!

Edited by renfr, 31 December 2012 - 07:31 PM.

[NZT48_User]

That beta lactoglobulin info is pretty interesting. Thanks for sharing that guys. I think I might take my Zi Cao with some chocolate milk. lol

[Nickthedevil]

Sigma aldrich sell the c16 model of PKRi, I'm going to suggest that at 0.1mg/kg for the price noone here (unless someone is a closet millionaire) is going to be able to produce more than a very limited case study into the human effects, given the mouse trials are ongoing, perhaps it would be more practical to participate in the process of the study, I'm sure if someone contacted DARPA we could get a human trial fast tracked. lol.

[kevinseven11]

I was just suggesting maybe ethanol would work, but yeah perhaps we could have someone buy a whey protein because I think casein may hinder absorption whether its total absorbed amount or if its slowing its speed.

[NZT48_User]

I don't see anything about ethanol in the β-lactoglobulin article. I would not drink ethanol with the Zi Cao even if it did help. I just can't stand any kind of drugs that negatively affect my brain patterns.

[renfr]

That beta lactoglobulin info is pretty interesting. Thanks for sharing that guys. I think I might take my Zi Cao with some chocolate milk. lol

how did it go with the milk?

[kevinseven11]

Ethanol is one of the most common solvents. Since this chemical is organic I assume it could be disolved into it. Not alot of ethanol is needed, plus you can just dehydrate it and make ~pure. Zi Cao probably needs a perfect dose or else the effects arn't good. Im surprised why this isn't used for memory.

[NZT48_User]

I'm not getting a whole lot of fascinating results. I'm still slowly upping the dose. I'll keep the ethanol thing in my notes for now.

[renfr]

http://onlinelibrary...100104/abstract
Liposomal shikonin as a new way to deliver the active component and reduce side effects.

Edited by renfr, 08 January 2013 - 12:37 AM.

[NZT48_User]

So liposomal delivery would make the shikonin more soluble in water.

I'm wondering if shikonin can cross the blood-brain barrier to have an effect on the brain.

http://www.plosone.o...al.pone.0022510
According to this article, shikonin increases skeletal muscle glucose uptake through stimulating the translocation of GLUT4 from intracellular vesicles.

http://diabetes.diab...ent_2/S131.full
"the insulin receptor, GLUT4, and GLUT8 are densely expressed in areas supporting cognition (such as the hippocampus). More interestingly, numerous lines of evidence suggest that an increased prevalence of insulin resistance similar to that seen in type 2 diabetes may contribute to the pathophysiology of Alzheimer’s disease"

So the above information would suggest that since shikonin stimulates the translocation of GLUT4, it would increase muscular strength, increase cognition in at least the hippocampus, and benefit those with diabetes 2 and Alzheimer's(if shikonin can cross the BBB in the first place).


Obviously there is a lot of research already put into the anti-cancer aspect of shikonin. Hopefully, over time, they will expand their research into brain effects of shikonin.

Edited by NZT48_User, 08 January 2013 - 09:22 PM.

[kevinseven11]

This has been researched in the brain and appears to be nootropic :
http://www.sciencedi...014299910005972
Protects brain
http://en.cnki.com.c...XB198804001.htm
Shows that distrubution of it is low in brain while high in skin. (Bad news)
http://link.springer...2977668?LI=true
Is an MAOI
http://www.sciencedi...304383503002398
Inhibits epidermal growth factor (keep in mind that ngf does thid too)

This compound needs to be extracted.

[renfr]

Shikonin may not cross the BBB but acetylshikonin might. (it's also present in Zi Cao)
http://www.biomedcen...71-2377/9/S1/S3
Interesting link about characteristics of BBB crossing drugs.

A low molecular weight and high degree of lipid solubility favor crossing by this mechanism. However, a drug taken up by the membranes that form the BBB must then partition into the aqueous environment of the brain's interstitial fluid to exert an effect.

Shikonin sure is soluble in lipids, I tried that and it does dissolve in lipids. I don't know about water.

But from the studies posted by kevinseven we can see that it seems to cross the BBB.

Btw, I have tried the other day to mix up in nut oil 70mg of Zi cao, it did pretty well. I just did that microdose to test an allergy reaction, nothing occured.
I just took 250mg Zi cao 5:1 extract right now, I hard an hard time mixing it with milk, it didn't mix totally maybe I should have used more milk.
Let's see what it does. I will try that same dose with oil, more milk and ethanol to see which seems to be the most efficient.

[NZT48_User]

I'm hoping that it's having some sort of long-term effect. I've been taking just Pramiracetam and Zi Cao for a few weeks. I just noticed today that my anxiety-prone mindset had been gone shortly after the Zi Cao regimen. It's hard to notice something that's not there. Ha Ha. Maybe it's a fluke?

I want to take the Zi Cao with lipids.
You think nuts are an adequate source for lipids? Mixing the ingredients in the stomach is reasonable, right?

[renfr]

I took nut oil because it was the only healthy oil I had in the kitchen, I guess it doesn't matter whether it is fish oil, nut oil, olive oil, etc... they're all very good sources of lipids and the Zi Cao should mix with it. Also it doesn't cause stomach upset.
What have you been taking with the Zi Cao? oil, water?
Maybe is it the pramiracetam that removed your anxiety, I heard it has anxyolitic properties.

Been 1 hour I took Zi Cao, no apparent effects for the moment. It didn't change my vision, no blood pressure or heart beat changes.
However it relieved my stuffy nose and cooled my forehead. As for memory, I don't know, I should try taking it while studying, probably this evening.
It's quite normal I don't have a lot of effects now as I took only the equivalent of 1250mg of the herb while the recommended dosage is between 3-9g.

Edited by renfr, 09 January 2013 - 05:52 AM.

[bernard]

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

What the hell are you talking about
The one at santa cruz costs $105. That's nothing but cheap.
The one at sigma-aldrich costs 307euro for 25mg which at the 3.7mcg/kg is a 125 day supply for a 65kg person. This is 2.45 euro/day. It's free. Are you kidding me ?
You expect to get cutting-edge science chemicals that took tens of years to develop for free. Human performance optimization and transhumanism were never for beggars. Give me a break, it's pathetic...

Sucking on some zi cao roots or whatever won't do sh*t in that particular case. Most likely orally ingested PKRi fractions won't even survive the first liver pass, let alone pass the BBB.

I took nut oil because it was the only healthy oil I had in the kitchen, I guess it doesn't matter whether it is fish oil, nut oil, olive oil, etc... they're all very good sources of lipids and the Zi Cao should mix with it. Also it doesn't cause stomach upset.
What have you been taking with the Zi Cao? oil, water?
Maybe is it the pramiracetam that removed your anxiety, I heard it has anxyolitic properties.

Been 1 hour I took Zi Cao, no apparent effects for the moment. It didn't change my vision, no blood pressure or heart beat changes.
However it relieved my stuffy nose and cooled my forehead. As for memory, I don't know, I should try taking it while studying, probably this evening.
It's quite normal I don't have a lot of effects now as I took only the equivalent of 1250mg of the herb while the recommended dosage is between 3-9g.

Lol... You took below the minimum suggested dose and you expect effects ? Not even enough for placebo...

Edited by Tatsumaru, 09 January 2013 - 03:58 PM.

[NZT48_User]

There's nothing wrong with taking herbs. And yes, we're all beggars dude. Lol. If someone wants to buy the pure stuff and record their results, that would be very cool. That's what this thread is for.

[renfr]

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

What the hell are you talking about
The one at santa cruz costs $105. That's nothing but cheap.
The one at sigma-aldrich costs 307euro for 25mg which at the 3.7mcg/kg is a 125 day supply for a 65kg person. This is 2.45 euro/day. It's free. Are you kidding me ?
You expect to get cutting-edge science chemicals that took tens of years to develop for free. Human performance optimization and transhumanism were never for beggars. Give me a break, it's pathetic...

Sucking on some zi cao roots or whatever won't do sh*t in that particular case. Most likely orally ingested PKRi fractions won't even survive the first liver pass, let alone pass the BBB.

I took nut oil because it was the only healthy oil I had in the kitchen, I guess it doesn't matter whether it is fish oil, nut oil, olive oil, etc... they're all very good sources of lipids and the Zi Cao should mix with it. Also it doesn't cause stomach upset.
What have you been taking with the Zi Cao? oil, water?
Maybe is it the pramiracetam that removed your anxiety, I heard it has anxyolitic properties.

Been 1 hour I took Zi Cao, no apparent effects for the moment. It didn't change my vision, no blood pressure or heart beat changes.
However it relieved my stuffy nose and cooled my forehead. As for memory, I don't know, I should try taking it while studying, probably this evening.
It's quite normal I don't have a lot of effects now as I took only the equivalent of 1250mg of the herb while the recommended dosage is between 3-9g.

Lol... You took below the minimum suggested dose and you expect effects ? Not even enough for placebo...

Your post is pure BS.
C16 hasn't been studied at all, studies are extremely scarce and it was never tested on humans.
We don't know it's side effects, we don't know the active dose for humans, we don't know its safety.
Zi Cao has been used by humans for thousands of years, it seems to be quite safe and there are a lot of studied about it.
C16 has to be stored in an extremely cold environment, its absorption is unknown and it must be injected.
The price is in fact irrelevant, C16 is quite cheap per dose but who would take the risk to inject a drug whose effects are unknown and whose dosage is extremely small?
Zi Cao may or may not work, time will tell, even if it doesn't work, it's much much safer than C16 and easily purchasable.
I took the minimum suggested dose with the perspective of using higher dosages...
Also I took into consideration the study with beta lactoglobulin enhancing absorption.
But hey, if you think ZI Cao is worthless and C16 is great then do .the experience for us

[bernard]

There's nothing wrong with taking herbs. And yes, we're all beggars dude. Lol. If someone wants to buy the pure stuff and record their results, that would be very cool. That's what this thread is for.

I'm willing to buy and try C16 and log my experience. Just let me know what the dosage is.

Zi Cao has been used by humans for thousands of years, it seems to be quite safe and there are a lot of studied about it.

So ? Who care if it's safe if it doesn't do sh*t.

C16 has to be stored in an extremely cold environment, its absorption is unknown and it must be injected.

I admit that I did laugh out loud at this comment. C16 has to be stored at -20C. Most household freezers maintain temperatures from (-23 to -18 °C). If that's extreme for you I wonder what you'd call a siberian winter.

Oh no, it has to be injected. No, mommy I hate injections. I want a candy. :D :D

The price is in fact irrelevant, C16 is quite cheap per dose but who would take the risk to inject a drug whose effects are unknown and whose dosage is extremely small?
Zi Cao may or may not work, time will tell, even if it doesn't work, it's much much safer than C16 and easily purchasable.

First you say that C16 is of unknown safety, now you say that Zi Cao is safer ? You lost me here.
You say that Zi Cao has been used for thousands of years, but that time will show whether it's effective or not ? I think Zi Cao had somewhat enough time to prove itself lol.

[renfr]

There's nothing wrong with taking herbs. And yes, we're all beggars dude. Lol. If someone wants to buy the pure stuff and record their results, that would be very cool. That's what this thread is for.

I'm willing to buy and try C16 and log my experience. Just let me know what the dosage is.

Zi Cao has been used by humans for thousands of years, it seems to be quite safe and there are a lot of studied about it.

So ? Who care if it's safe if it doesn't do sh*t.

C16 has to be stored in an extremely cold environment, its absorption is unknown and it must be injected.

I admit that I did laugh out loud at this comment. C16 has to be stored at -20C. Most household freezers maintain temperatures from (-23 to -18 °C). If that's extreme for you I wonder what you'd call a siberian winter.

Oh no, it has to be injected. No, mommy I hate injections. I want a candy. :D :D

The price is in fact irrelevant, C16 is quite cheap per dose but who would take the risk to inject a drug whose effects are unknown and whose dosage is extremely small?
Zi Cao may or may not work, time will tell, even if it doesn't work, it's much much safer than C16 and easily purchasable.

First you say that C16 is of unknown safety, now you say that Zi Cao is safer ? You lost me here.
You say that Zi Cao has been used for thousands of years, but that time will show whether it's effective or not ? I think Zi Cao had somewhat enough time to prove itself lol.

If you don't know what the dosage is then you just shouldn't try things like that.
No one even knows if it crosses the BBB, usually such studies inject directly into the brain and not through the bloodstream. Are you going to open your skull and inject that stuff? Yeah sure, you're such a laughingstock.
When I said time, I was talking about what we're doing right now.
Please go away from this thread, you're just making a fool of yourself.

[bernard]

If you don't know what the dosage is then you just shouldn't try things like that.
No one even knows if it crosses the BBB, usually such studies inject directly into the brain and not through the bloodstream. Are you going to open your skull and inject that stuff? Yeah sure, you're such a laughingstock.
When I said time, I was talking about what we're doing right now.

Dude, you don't even know what you are talking about...

All animal care and procedures were carried out in accordance with local guidelines. All efforts were made to minimize animal suffering and discomfort. To determine the highest activation of PKR, Sprague-Dawley rats of 7-day, 1, 2, 4, 6, 9 and 12-month-old were used. Seven-day-old rats were intraperitoneally (ip) injected with a single dose (200 μL) of C16 at the concentrations of 0.335, 3.35, 33.5 or 167.5 μg/kg of body weight. Animal well-being is controlled by keeping a close eye on behavioural aspects (fear, aggressiveness, suffering, and pain). Injection of C16 at 335 μg/kg of body weight was shown to be lethal. Stocked solutions of C16 were prepared in DMSO (final concentration: 0.5%). Control rat pups were injected with 0.5% DMSO. Animals were decapited at 3 h, 6 h and 9 h post-treatment after isoflurane anaesthesia.

Source: http://www.sciencedi...014579307008952

What are you even arguing about. Obviously you don't even know how C16 was administered. I just entered this topic and I already know more about this compound than you do. (And I know next to nothing...)

There is no such thing like "When I said time I meant that". For a thousand years people should've noticed all effects period. The same way people noticed the effects of Gingko Biloba, Lion's Mane, Gotu Kola and whatnot.

Please go away from this thread, you're just making a fool of yourself.

You sure ? Sounds more like you are beginning to feel embarassed...
Don't sweat it dude. Take some Zi Cao and chillax.

[renfr]

No, you are just polluting this thread with bullshit that's all.
If you really want to try out C16 then do it and post your results, until then any discussion is pointless.

[bernard]

No, you are just polluting this thread with bullshit that's all.
If you really want to try out C16 then do it and post your results, until then any discussion is pointless.

No, actually you are polluting it. The original thread was started on C16, you are talking about nonsense herbal remedies and "safe" alternatives. If someone is 100% bs that'd be you.

[NZT48_User]

Guys, this whole argument needs to be diffused right now. Both methods of administration are worth at least considering. They both have positive and negative points. Let's change the subject to something less hostile.

[bernard]

Guys, this whole argument needs to be diffused right now. Both methods of administration are worth at least considering. They both have positive and negative points. Let's change the subject to something less hostile.

I agree. Thanks.