57 replies to this topic

[William Sterog]

1 - Neurotransmitters:

 

Depression has been linked to problems or imbalances in the brain with regard to the neurotransmitters serotonin, norepinephrine, and dopamine. [...] What we do know is that antidepressant medications (used to treat the symptoms of depression) are known to act upon these particular neurotransmitters and their receptors.

 

https://www.mentalhe...rotransmitters/

 

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The discovery of Yuanzhi-1, a triterpenoid saponin derived from the traditional Chinese medicine, has antidepressant-like activity.

 

Yuanzhi, the dried root of Polygala tenuifolia Willd., is a well-known traditional Chinese medicine used for its sedative, antipsychotic, cognitive improving, neuroprotective, and antidepressant effects. Yuanzhi-1 (1 nM) had a high affinity for serotonin, norepinephrine and dopamine transporters. Acute toxicity tests indicated that the LD50 of Yuanzhi-1 (86.5mg/kg) was similar to that of duloxetine (73.2 mg/kg). These findings demonstrate that Yuanzhi-1 has a potential to be a novel triple monoamine reuptake inhibitor of antidepressant-like activity.

 

http://www.ncbi.nlm....pubmed/24614095

 

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Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of themonoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression.^[1]

 

^{https://en.wikipedia...idase_inhibitor}

 

->

 

Possible mechanism of the antidepressant effect of 3,6'-disinapoyl sucrose from Polygala tenuifolia Willd.

 

DISS significantly inhibited MAO-A and MAO-B activity and blocked plasma elevated cortisol level, an indicator of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, DISS increases SOD activity, inhibits lipid peroxidation, and lessens production of MDA.

CONCLUSION:

These results suggest that DISS may possess potent and rapid antidepressant properties, which are mediated via MAO, the HPA axis and oxidative systems. These antidepressant actions make DISS a potentially valuable drug for the treatment of depression.

 

http://www.ncbi.nlm....pubmed/21585386

 

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2 - NGF, BDNF and the hippocampus:

 

Nerve growth factor (NGF) has novel antidepressant-like properties in rats.

 

NGF has antidepressant-like effects but does not appear to have biochemical actions typical of other antidepressants.

 

http://www.ncbi.nlm....pubmed/19945476

 

+

 

Exposure to stress and the stress hormone corticosterone has been shown to decrease the expression of BDNF in rats, and, if exposure is persistent, this leads to an eventual atrophy of the hippocampus. Atrophy of the hippocampus and other limbic structures has been shown to take place in humans suffering from chronic depression.^[68] In addition, rats bred to be heterozygous for BDNF, therefore reducing its expression, have been observed to exhibit similar hippocampal atrophy. This suggests that an etiological link between the development of depression and BDNF exists. Supporting this, the excitatory neurotransmitter glutamate, voluntary exercise,^[69] caloric restriction, intellectual stimulation, curcumin^[70] and various treatments for depression (such as antidepressants^[71] and electroconvulsive therapy^[72]) increase expression of BDNF in the brain. In the case of some treatments such as drugs^[73] and electroconvulsive therapy^[74] this has been shown to protect against or reverse this atrophy.^[73]

 

^{https://en.wikipedia...ctor#Depression}

 

^->

 

Induction of NGF synthesis in astrocytes by onjisaponins of Polygala tenuifolia, constituents of kampo (Japanese herbal) medicine, Ninjin-yoei-to.

 

Onjisaponins A, B, E, F and G as major saponins of the root of P. tenuifolia strongly increased the NGF level.

 

http://www.ncbi.nlm....pubmed/12725562

 

Enhancements of choline acetyltransferase activity and nerve growth factor secretion by Polygalae radix-extract containing active ingredients in Kami-untan-to.

 

These results suggest that Polygala radix¹ has an important role on the enhancing effects of KUT on ChAT activity and NGF secretion.

 

http://www.ncbi.nlm....pubmed/23195476

 

¹ Radix Polygalae (the root of Polygala tenuifolia) 

 

Neuroprotective effects of 3,6'-disinapoyl sucrose through increased BDNF levels and CREB phosphorylation via the CaMKII and ERK1/2 pathway.

 

3,6'-Disinapoyl sucrose (DISS) is an oligosaccharide ester natural product originating from the root of wild Polygala tenuifolia. [...] The results from the present study suggest that DISS-mediated regulation of BDNF gene expression is associated with CREB-mediated transcription of BDNF and upstream activation of ERK1/2 and CaMKII. Finally, DISS may exert neuroprotective and antidepressant effects through these signaling pathways in neuronal cells.

 

http://www.ncbi.nlm....pubmed/24488601

 

Effect of Tenuifoliside A isolated from Polygala tenuifolia on the ERK and PI3K pathways in C6 glioma cells.

 

TFSA increased levels of phospho-ERK and phospho-Akt, enhanced release of BDNF, which were blocked by ERK and PI3K inhibitors, respectively (U0126 and LY294002).

 

http://www.ncbi.nlm....pubmed/24877714

 

Tenuigenin promotes proliferation and differentiation of hippocampal neural stem cells.

 

The present study was to investigate the influence of tenuigenin, an active ingredient of Polygala tenuifolia Willd, on the proliferation and differentiation of hippocampal neural stem cells in vitro. [...] These findings suggest that tenuigenin is involved in regulating the proliferation and differentiation of hippocampal neural stem cells. This result may be one of the underlying reasons for tenuigenin's nootropic and anti-aging effects.

 

http://www.ncbi.nlm....pubmed/22179853

 

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3 - NMDA:

 

 

Targeting of NMDA receptors in the treatment of major depression.

 

Major depressive disorder (MDD) is a common, recurrent mental illness that affects millions of people worldwide. Accumulating evidence suggests that the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptors, plays an important role in the neurobiology and treatment of this disease. Currently, the non-competitive NMDA receptor antagonist ketamine is considered as one of the most attractive candidate drugs in therapy of treatment-resistant depression. A recent study demonstrated ketamine's rapid antidepressant activity in patients with treatment-resistant MDD and bipolar disorder.

 

http://www.ncbi.nlm....pubmed/24410564

 

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Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract.

 

Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects.

 

0.1mg/kg of the root has been noted to have potency comparable to 10mg/kg IV ketamine in mice.

 

http://www.ncbi.nlm....pubmed/24520403

 

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Edited by William Sterog, 27 March 2016 - 08:44 AM.

[chemicalambrosia]

Good post, but does anyone have good experience with this herb or are there any Western studies? I think all the studies are Chinese(questionable) and performed on animals. If the herb works a Western supplement company needs to make a good standardized extract .

[William Sterog]

Good post, but does anyone have good experience with this herb or are there any Western studies? I think all the studies are Chinese(questionable) and performed on animals. If the herb works a Western supplement company needs to make a good standardized extract .

 

I just bought 40g of 10:1 extract from a chinese supplier. In 45-60 days I will have it here and I'm gonna try to do some heavy metal accumulation test and then report my personal experience. 

 

I experimented a lot with Uncaria Rhynchophylla, an herb that I found pretty similar, and it makes me happy, I never read about this possible effect.

 

I talk a little bit about it on this topic: http://www.longecity...e-of-cats-claw/

[normalizing]

thats a long time till you get it. is it that difficult to order from US source? i believe i have seen some on amazon and various herb stores online sell various types

[William Sterog]

thats a long time till you get it. is it that difficult to order from US source? i believe i have seen some on amazon and various herb stores online sell various types

I life in Spain, chinese ship is free, ships from Amazon.com are crazy expensive.

[stillwater]

I found some of this in dried root form in a store close to me. I'm going to turn some of it into a water decoction for quicker use and the rest into an alcohol based tincture which will take a few weeks. I'll report my findings.

 

[sativa]

I also have some of this.

Here is a link with more info
https://examine.com/...ala-tenuifolia/

[sativa]

[Double.post]

Edited by sativa, 06 April 2016 - 09:02 PM.

[stillwater]

I've done the water decoction a few times with this and unfortunately it didn't produce any results , positive or negative. I made an alcohol extract but it won't be ready for a few more weeks. 

 

[normalizing]

it figures too much fuzz about nothing. all the praise comes from china anyway with speculative positive results. if some reliable unsupported by supplement company study done in the west shows positive, then it might have SOME probability

[William Sterog]

it figures too much fuzz about nothing. all the praise comes from china anyway with speculative positive results. if some reliable unsupported by supplement company study done in the west shows positive, then it might have SOME probability

Some of the research has been made on Japan. This herb looks almost too good to be true, I agree. Anyway, I will update this topic when it arrives, I do not sell anything nor have any particular interest in this herb, so I'll try to be objective in my N=1 study.

[Heisenburger]

Nootropics Depot just started carrying it. I'm reading up on it now.

[normalizing]

william sterog what happened, it arrived or not and whats your update?

[William Sterog]

Nootropics Depot just started carrying it. I'm reading up on it now.

I came here to comment the same thing.

william sterog what happened, it arrived or not and whats your update?

Yes, it was a shitty extract that smelled like curry and gave me a rush and a numb sensation in my left arm. So I'm gonna order the one from ND because they sell top quality products. I'm gonna order some Lion's Mane too, I believe that you were also interested in this mushroom, 120 servings for 9.99$, and I believe that it will synergize well with the Polygala.

I hope this time it doesn't feel like poison.

[normalizing]

lol where did you get that shitty extract from, China?

[William Sterog]

lol where did you get that shitty extract from, China?

Yes, of course. First and last time using Aliexpress.

[Heisenburger]

I bought a bottle and gave it a try. Definitely seems to be doing something. Been having stronger-than-usual problems for the past couple of weeks with motivation and anxiety. Seems to help a lot with the motivation problems and a little bit with the anxiety issues. And amazingly enough, it doesn’t taste horrible. It actually has a very mild chocolaty/coffee flavor. It’s pretty inexpensive, so I’d say give it a shot if you’re suffering from depression and/or anxiety.

[Heisenburger]

This stuff is really doing wonders for me. Here is an exact copy of a text message that I just sent to a friend of mine a couple of hours ago:

 

You really have got to try this herb I’ve been taking. Something is really happening here. First of all, my anxiety is gone. Not diminished, GONE. Secondly, something amazing happened to me this morning. I was drinking my morning coffee and sending out my form letters. Suddenly I felt something that I haven’t felt in a long, long, long time—euphoria. Not like a drug-induced euphoria, but like a sense of real contentment and euphoria. The same type of euphoria that existential psychologists refer to as “self-actualization.”

 

It only lasted for a few seconds and then was gone. I really hope it comes back again. It was wondrous. I haven’t had a peak experience since I was in my twenties. However, I did have one when I was in my mid-thirties while standing at a crosswalk. It lasted about half a minute. That was the last one I ever had until this morning.

Edited by Heisenburger, 08 September 2016 - 07:38 PM.

[sativa]

I've tried Polygala twice so far, its definitely a genuine extract (1:10 extract ratio) and has noticeable effects.

My intent for use is purely psychoactive and exploratory in nature.

My last dose was equivalent to 10g and this was very noticeable... More exploring to be done

[William Sterog]

I agree, this herb is awesome, this is my fourth day in it. It is maybe the most noticiable nootropic I've ever tried. I find myself singing happily or reading, writing, drawing or playing the guitar a lot more, I just don't want anymore to stay in bed watching Family Guy or any other crap.

I dose it sublingually and I feel it kicking in in a short time, I believe that this can have even have abuse potential. Also, the flavor is incredible, like a potent dark chocolate.

[sentics]

what's a good source? did you all get it from alibaba?

[William Sterog]

what's a good source? did you all get it from alibaba?

Nootropics Depot.

[Heisenburger]

Also, the flavor is incredible, like a potent dark chocolate.

 

Yeah, that’s the really amazing thing about it—it’s actually tasty! Slightly sweet with chocolate and coffee notes.

 

[jaiho]

This stuff is really doing wonders for me. Here is an exact copy of a text message that I just sent to a friend of mine a couple of hours ago:

 

You really have got to try this herb I’ve been taking. Something is really happening here. First of all, my anxiety is gone. Not diminished, GONE. Secondly, something amazing happened to me this morning. I was drinking my morning coffee and sending out my form letters. Suddenly I felt something that I haven’t felt in a long, long, long time—euphoria. Not like a drug-induced euphoria, but like a sense of real contentment and euphoria. The same type of euphoria that existential psychologists refer to as “self-actualization.”

 

It only lasted for a few seconds and then was gone. I really hope it comes back again. It was wondrous. I haven’t had a peak experience since I was in my twenties. However, I did have one when I was in my mid-thirties while standing at a crosswalk. It lasted about half a minute. That was the last one I ever had until this morning.

 

I know that feeling, ive only been able to get it on an SSRI + TCA combination.

I have polygala here with me to try, what doses are you guys using?

[Heisenburger]

The label on my tub (from Noots Depot) suggests 100 mg. t.i.d., so that’s what I’ve been taking. One-thirty-second of a teaspoon, lightly tamped and struck off with the edge of a sharp metal spatula, is exactly 100 mgs. I was a little alarmed at the OP’s suggestion that it could have abuse potential, so I tried a massive dose to see if it would get me high. It didn’t. It doesn’t appear to lock into the brain’s reward circuitry, which I found both relieving and encouraging. The euphoria I felt yesterday morning was a real, natural, peak experience. Along with GTS-21, this stuff is the find of the year. [Major Pessimism Mode]Of course, in a couple of months somebody is going to publish a paper demonstrating that it is massively hepatotoxic[/Major Pessimism Mode]…

[William Sterog]

The label on my tub (from Noots Depot) suggests 100 mg. t.i.d., so that’s what I’ve been taking. One-thirty-second of a teaspoon, lightly tamped and struck off with the edge of a sharp metal spatula, is exactly 100 mgs. I was a little alarmed at the OP’s suggestion that it could have abuse potential, so I tried a massive dose to see if it would get me high. It didn’t. It doesn’t appear to lock into the brain’s reward circuitry, which I found both relieving and encouraging. The euphoria I felt yesterday morning was a real, natural, peak experience. Along with GTS-21, this stuff is the find of the year. [Major Pessimism Mode]Of course, in a couple of months somebody is going to publish a paper demonstrating that it is massively hepatotoxic[/Major Pessimism Mode]…

It is awesome that you tried that, and I like the fact that it didn't act like a drug, I was a little concerned about this too. Another concerns about it are:

8.1. Liver

Polygala tenuifolia ethanolic root extract has been shown to activate peroxisome proliferator response element (PPRE) activity in Sk-hep1 liver cells in a concentration dependent manner at 100 µg/mL or above, suggesting that it may promote fatty acid oxidation.[70] Curiously, this same extract promoted lipid accumulation in a medium containing Alcohol (to promote lipid accumulation) as assessed by Nile red staining,[70] suggesting that Polygala tenuifolia may actually promote lipid accumulation in vitro through unknown mechanisms.

10.1. Seminal Properties

High concentrations of water extract from Polygala tenuifolia applied directly to semen appears to possess rapid-acting spermicidal properties, with 10-20mg/mL causing absolute immobilization and lysis of all sperm cells and 5mg/mL immobilizing 39.5+/-3.2% of sperm.[73]

Polygala tenuifolia has potent spermicidal effects when applied directly to sperm. There are currently no studies assessing the effects of oral ingestion on fertility, which is not known.

Do you feel anything weird going on downthere?

[sativa]

I would think that applying "high concentrations" of Polygala directly to sperm as opposed to oral administration where doses apparently are around 3-9g IIRC (stomach acid and enzymes processing etc) would be very different.

For those of you who can perceive traditional Chinese medicinal terminology and concepts (or "convert" them to western concepts) this site has insightful information on Polygala:

http://old.tcmwiki.c...radix-polygalae

Edited by sativa, 10 September 2016 - 08:53 AM.

[William Sterog]

I would think that applying "high concentrations" of Polygala directly to sperm as opposed to oral administration where doses apparently are around 3-9g IIRC (stomach acid and enzymes processing etc) would be very different.

For those of you who can perceive traditional Chinese medicinal terminology and concepts (or "convert" them to western concepts) this site has insightful information on Polygala:

http://old.tcmwiki.c...radix-polygalae

Yes, I am aware of that, but a lot of herbs are antiandrogenic: reishi, bacopa, centella... so who knows. Also, am I the only one taking it sublingually?

[sativa]

Indeed!
I also agree that this has potential for recreational effects especially when combined with other substances...

[nicklesprout]

Nobody is concerned with tolerance, withdrawal, or poop out in association with long term chronic usage of this stuff?