19 replies to this topic

[Ark]

<sup>I started researching North American Skullcap and came across PREP and Baicalin.




Prolyl endopeptidase (PREP) or prolyl oligopeptidase, sometimes post-proline cleaving enzyme) is a large cytosolic enzyme that belongs to a distinct class of serine peptidases. It was first described in the cytosol of rabbit brain as an oligopeptidase, which degrades the nonapeptide bradykinin at the Pro-Phe bond.[1] The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides such as alpha-melanocyte-stimulating hormone, luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone, angiotensin, neurotensin, oxytocin, substance P and vasopressin. PREP cleaves peptide bonds at the C-terminal side of proline residues. Its activity is confined to action on oligopeptides of less than 10 kD and it has an absolute requirement for the trans-configuration of the peptide bond preceding proline.
Some types of prolyl endopeptidase have been used in studies to decrease the propensity of gluten-containing wheat products to aggravate coeliac disease.[2] However, orally administered enzymes are potentially subject to inactivation in the gastrointestinal tract.[3]
In humans prolyl endopeptidase] is encoded by the PREP gene.[4][5] The protein encoded by this gene is a cytosolic prolyl endopeptidase that cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. Prolyl endopeptidases have been reported to be involved in the maturation and degradation of peptide hormones and neuropeptides.[5] There's an indication that altered PREP activity is associated with autism spectrum disorders and various psychological diseases such as schizophrenia, mania and clinical depression.[6]</sup>


Inhibitors
^{Several prolyl endopeptidase inhibitors are known,nootropic and antidepressant drugs.Baicalin[11]}

^JTP-4819[12]

^KYP-2047[13]

^Berberine

^{During my short useage skullcap, I've found it to be a calming in a higher sense of awarness sort of way. I'm currently stacking St johns wort and Ginko, for greater effect. I may also Add Berberine too amp up the PREP effect.}

[Ark]

Mods please move to Brain Health Forum !


~THANK YOU~

[Lufega]

I'm also interested in this and I wonder why this isn't discussed more in the Nootropics arena. I've used rosemary before and the effect is nice and mild. Berberine was way stronger. I had forgotten about this concept until I used Berberine again for something else and noticed the cognitive effects. I'm curious to try rosmarinic acid (another inhibitor) alone of combine with skullcap but I might just stick to berberine since it worked so well.

I'll post this study that I found interesting. If you benefit greatly from using PEi, the reason might be related to some sort of brain damage/inflammation rather than amyloid buildup.

Brain prolyl oligopeptidase activity is associated with neuronal damage rather than beta-amyloid accumulation.


Abstract

Prolyl oligopeptidase (POP) have been suggested to participate in the pathogenesis of Alzheimer's disease (AD). In this study the activity of POP is evaluated in AD patients and in transgenic mice with substantial deposits of beta-amyloid (Abeta). In AD cases, the POP activity displayed a significant negative correlation with the scores of senile/neuritic plaques and neurofibrillary tangles but not with Abeta-load. The transgenic mice with high levels of Abeta did not have altered POP activity compared to wild type mice. Based on our results, the low POP activity in AD seems to be associated with neuronal degeneration rather than to Abeta accumulation.

[Ark]

I'm also interested in this and I wonder why this isn't discussed more in the Nootropics arena. I've used rosemary before and the effect is nice and mild. Berberine was way stronger. I had forgotten about this concept until I used Berberine again for something else and noticed the cognitive effects. I'm curious to try rosmarinic acid (another inhibitor) alone of combine with skullcap but I might just stick to berberine since it worked so well.

I'll post this study that I found interesting. If you benefit greatly from using PEi, the reason might be related to some sort of brain damage/inflammation rather than amyloid buildup.

Brain prolyl oligopeptidase activity is associated with neuronal damage rather than beta-amyloid accumulation.


Abstract

Prolyl oligopeptidase (POP) have been suggested to participate in the pathogenesis of Alzheimer's disease (AD). In this study the activity of POP is evaluated in AD patients and in transgenic mice with substantial deposits of beta-amyloid (Abeta). In AD cases, the POP activity displayed a significant negative correlation with the scores of senile/neuritic plaques and neurofibrillary tangles but not with Abeta-load. The transgenic mice with high levels of Abeta did not have altered POP activity compared to wild type mice. Based on our results, the low POP activity in AD seems to be associated with neuronal degeneration rather than to Abeta accumulation.

PREP This enzyme is involved in the metabolic breakdown of a number of neuropeptide neurotransmitters in the brain, which also might be the root of why it makes me feel good.

[Ampa-omega]

Good stuff, I like hearing about new discussion like this. I assume its from skullcap?

[5] There's an indication that altered PREP activity is associated with autism spectrum disorders and various psychological diseases such as schizophrenia, mania and clinical depression.

Edited by Ampa-omega, 16 February 2012 - 12:50 AM.

[Ark]

.

Edited by Ark, 16 February 2012 - 08:32 AM.

[Ark]

I'm also interested in this and I wonder why this isn't discussed more in the Nootropics arena. I've used rosemary before and the effect is nice and mild. Berberine was way stronger. I had forgotten about this concept until I used Berberine again for something else and noticed the cognitive effects. I'm curious to try rosmarinic acid (another inhibitor) alone of combine with skullcap but I might just stick to berberine since it worked so well.

I'll post this study that I found interesting. If you benefit greatly from using PEi, the reason might be related to some sort of brain damage/inflammation rather than amyloid buildup.

Brain prolyl oligopeptidase activity is associated with neuronal damage rather than beta-amyloid accumulation.


Abstract

Prolyl oligopeptidase (POP) have been suggested to participate in the pathogenesis of Alzheimer's disease (AD). In this study the activity of POP is evaluated in AD patients and in transgenic mice with substantial deposits of beta-amyloid (Abeta). In AD cases, the POP activity displayed a significant negative correlation with the scores of senile/neuritic plaques and neurofibrillary tangles but not with Abeta-load. The transgenic mice with high levels of Abeta did not have altered POP activity compared to wild type mice. Based on our results, the low POP activity in AD seems to be associated with neuronal degeneration rather than to Abeta accumulation.

Good stuff, I like hearing about new discussion like this. I assume its from skullcap?

[5] There's an indication that altered PREP activity is associated with autism spectrum disorders and various psychological diseases such as schizophrenia, mania and clinical depression.

An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers.

Wolfson P, Hoffmann DL.

Source

Phytos Inc., San Anselmo, Calif., USA.

Abstract

Scutellaria lateriflora is an herbal medicine with long-standing traditional use as a relaxing nervine. There has been controversy in the literature with regards to its efficacy, and this study was designed to clarify its effectiveness in reducing anxiety, one of the phytotherapeutic indications. A double blind, placebo-controlled study of healthy subjects demonstrated noteworthy anxiolytic effects.

http://www.ncbi.nlm....pubmed/12652886



This stuff is amazing, I look foreword to hearing some back some feedback from others?!

[ScienceGuy]

Scutellaria lateriflora...

This stuff is amazing, I look foreword to hearing some back some feedback from others?!

SKULLCAP (Scutellaria lateriflora)

SKULLCAP is akin to BENZODIAZEPINES, in that it is a GABA RECEPTOR AGONIST, in fact binding to the BENZODIAZEPINE RECEPTORS at the GABAA RECEPTOR.

Therefore prolonged usage for the medium to long-term is ill advised since this will induce down-regulation of the GABA RECEPTORS; and hence usage should be restricted exclusively to short-term use and/or CYCLING ON/OFF with the OFF period being sufficiently long such that status is allowed to fully return to basline

I should stress that it is perfectly safe to take SKULLCAP as long as usage be restricted exclusively to short-term use and/or CYCLING ON/OFF

See the following:

Phytomedicine. 2003 Nov;10(8):640-9.

Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties.

Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z.

Source
Ottawa-Carleton Institute of Biology, University of Ottawa, Ottawa, Canada.

Abstract
The phytochemistry and biological activity of Scutellaria lateriflora L. (American skullcap) which has been traditionally used as a sedative and to treat various nervous disorders such as anxiety was studied. In vivo animal behaviour trials were performed to test anxiolytic effects in rats orally administered S. laterifolia extracts. Significant increases in the number of entries into the center of an "open-field arena"; number of unprotected head dips, number of entries and the length of time spent on the open arms of the Elevated Plus-Maze were found. The identification and quantification of the flavonoid, baicalin in a 50% EtOH extract (40 mg/g) and its aglycone baicalein in a 95% EtOH extract (33 mg/g), as well as the amino acids GABA in H2O and EtOH extracts (approximately 1.6 mg/g) and glutamine in a H2O extract (31 mg/g), was performed using HPLC. These compounds may play a role in anxiolytic activity since baicalin and baicalein are known to bind to the benzodiazepine site of the GABAA receptor and since GABA is the main inhibitory neurotransmitter.

PMID: 14692724

[ScienceGuy]

^{I started researching North American Skullcap and came across PREP and Baicalin.}

Hey Ark,

Thank you for this VERY interesting post on PREP INHIBITION. Nice one!

It would be good to find a more SELECTIVE PREP INHIBITOR, given SKULLCAP is also a BENZODIAZEPINE RECEPTOR AGONIST

[Ark]

^{I started researching North American Skullcap and came across PREP and Baicalin.}

Hey Ark,

Thank you for this VERY interesting post on PREP INHIBITION. Nice one!

It would be good to find a more SELECTIVE PREP INHIBITOR, given SKULLCAP is also a BENZODIAZEPINE RECEPTOR AGONIST

http://www.dcscience...BJWellbeing.pdf

[ScienceGuy]

http://www.dcscience...BJWellbeing.pdf

Hey Ark,

Thank you for the additional study... very interesting!

Yes, this indeed further confirms the fact that SKULLCAP is a BENZODIAZEPINE / GABA RECEPTOR AGONIST, and as such its usage should be limited to short-term use or CYCLING ON/OFF in order to avoid DOWN-REGULATION of the GABA RECEPTORS

See the following extract from the full text:

British Journal of Wel. 2010 Jun;1(4):25-30

American skullcap (Scutellaria lateriflora): an ancient remedy for today’s anxiety?

Brock C., Whitehouse J., Tewfik I., Towell T.

Source

School of Life Sciences, University of Westminster, United Kingdom.

Extract from Full Text

Many orthodox anxiolytic treatments can have unwanted side effects. Benzodiazepines, for example, have been linked to muscle weakness, amnesia, headaches, vertigo, urinary retention, slurred speech and gastrointestinal disturbances. They may lead to tolerance and physical and psychological dependence, and are considered to be dangerous to use long–term (BNF, 2008)…

American skullcap (Scutellaria laterifl ora) (Figure 1) is one of the most commonly used herbs by western medical herbalists, particularly for anxiety and related conditions (Bergner, 2002–2003)…

Due to its potential sedative action (Greenfi eld and Davis, 2004), it may be advisable to refrain from using S. lateriflora in combination with other sedatives, such as alcohol and benzodiazepines. It is not possible to comment on the safety of its use in pregnancy…

Benzodiazepines are allosteric ligands for the GABAA receptor, a chloride channel that is gated by GABA. They bind to the benzodiazepine site of the GABAA receptor, thus increasing the affinity of the inhibitory neurotransmitter GABA for the GABA site of the GABAA receptor. This decreases the likelihood of action potentials by excitatory neurotransmitters (Rabow et al, 1995). One important study (Liao et al, 1998) indicated oroxylin A, baicalein and wogonin, which are flavonoids found in S. lateriflora, had weak affinities for the benzodiazepine site of GABAA receptors in mouse cerebral cortex in vitro. In another study Hui et al (2000) tested the capacity of baicalin, baicalein, scutellarein and wogonin to bind to the benzodiazepine site of the GABAA receptor in homogenised rat brain. Affinity to the benzodiazepine site for scutellarein was moderate and weak for baicalin. Contrary to results of the earlier study (Liao et al, 1998), the binding affinities of wogonin and baicalein [to the benzodiazepine receptors] were strong. The authors suggested the discrepancy may be due to differences in species and assay models used (Hui et al, 2000). The ability of the skullcap flavonoids to bind to the benzodiazepine site of the GABAA receptor suggests an anxiolytic effect for S. lateriflora…

[Ark]

http://www.dcscience...BJWellbeing.pdf

Hey Ark,

Thank you for the additional study... very interesting!

Yes, this indeed further confirms the fact that SKULLCAP is a BENZODIAZEPINE / GABA RECEPTOR AGONIST, and as such its usage should be limited to short-term use or CYCLING ON/OFF in order to avoid DOWN-REGULATION of the GABA RECEPTORS

See the following extract from the full text:

British Journal of Wel. 2010 Jun;1(4):25-30

American skullcap (Scutellaria lateriflora): an ancient remedy for today’s anxiety?

Brock C., Whitehouse J., Tewfik I., Towell T.

Source

School of Life Sciences, University of Westminster, United Kingdom.

Extract from Full Text

Many orthodox anxiolytic treatments can have unwanted side effects. Benzodiazepines, for example, have been linked to muscle weakness, amnesia, headaches, vertigo, urinary retention, slurred speech and gastrointestinal disturbances. They may lead to tolerance and physical and psychological dependence, and are considered to be dangerous to use long–term (BNF, 2008)…

American skullcap (Scutellaria laterifl ora) (Figure 1) is one of the most commonly used herbs by western medical herbalists, particularly for anxiety and related conditions (Bergner, 2002–2003)…

Due to its potential sedative action (Greenfi eld and Davis, 2004), it may be advisable to refrain from using S. lateriflora in combination with other sedatives, such as alcohol and benzodiazepines. It is not possible to comment on the safety of its use in pregnancy…

Benzodiazepines are allosteric ligands for the GABAA receptor, a chloride channel that is gated by GABA. They bind to the benzodiazepine site of the GABAA receptor, thus increasing the affinity of the inhibitory neurotransmitter GABA for the GABA site of the GABAA receptor. This decreases the likelihood of action potentials by excitatory neurotransmitters (Rabow et al, 1995). One important study (Liao et al, 1998) indicated oroxylin A, baicalein and wogonin, which are flavonoids found in S. lateriflora, had weak affinities for the benzodiazepine site of GABAA receptors in mouse cerebral cortex in vitro. In another study Hui et al (2000) tested the capacity of baicalin, baicalein, scutellarein and wogonin to bind to the benzodiazepine site of the GABAA receptor in homogenised rat brain. Affinity to the benzodiazepine site for scutellarein was moderate and weak for baicalin. Contrary to results of the earlier study (Liao et al, 1998), the binding affinities of wogonin and baicalein [to the benzodiazepine receptors] were strong. The authors suggested the discrepancy may be due to differences in species and assay models used (Hui et al, 2000). The ability of the skullcap flavonoids to bind to the benzodiazepine site of the GABAA receptor suggests an anxiolytic effect for S. lateriflora…

.
An in vivo behavioural test measuring the anxiolytic responses in rats administered aqueous extracts of skullcap showed a significant difference between treated and control rats (n=21, p<0.05) (17).
In vitro aqueous extracts of skullcap induced release of [3H] GABA in rat brain synaptosomes. Inhibition of GABA reuptake in cells explains the in vivo mechanism by which skullcap has an inhibitory effect on neurotransmission (17).
In vitro studies with baicalin and the aglycone baicalein from Scutellaria baicalensis demonstrate binding with high affinity to the benzodiazepine site of GABAA, contributing to the anxiolytic properties (17).

The discovery of relatively high quantities of serotonin in skullcap may explain the in vitro study, which found that skullcap extracts bind to the serotonin 5-HT7 receptor (8,18)
http://www.scu.edu.a...n/index.php/43/

Edited by Ark, 18 February 2012 - 09:28 PM.

[ScienceGuy]

An in vivo behavioural test measuring the anxiolytic responses in rats administered aqueous extracts of skullcap showed a significant difference between treated and control rats (n=21, p<0.05) (17).
In vitro aqueous extracts of skullcap induced release of [3H] GABA in rat brain synaptosomes. Inhibition of GABA reuptake in cells explains the in vivo mechanism by which skullcap has an inhibitory effect on neurotransmission (17).
In vitro studies with baicalin and the aglycone baicalein from Scutellaria baicalensis demonstrate binding with high affinity to the benzodiazepine site of GABAA, contributing to the anxiolytic properties (17).

The discovery of relatively high quantities of serotonin in skullcap may explain the in vitro study, which found that skullcap extracts bind to the serotonin 5-HT7 receptor (8,18)
http://www.scu.edu.a...n/index.php/43/

Hey Ark,

I'm not quite sure what point you are trying to make here... But to clarify, there is conclusive substantiated evidence from MULTIPLE studies that some of the consistuents within SKULLCAP most certainly function as BENZODIAZEPINE / GABA RECEPTOR AGONISTS, and as such it would be advisable to CYCLE usage ON/OFF (or limit usage to occasional short-term usage only) to avoid the potential for RECEPTOR DOWN-REGULATION

Furthermore, the fact that there also exists consituents within SKULLCAP that function as GABA REUPTAKE INHIBITOR further compounds this situation since GABA REUPTAKE INHIBITORS will also induce DOWN-REGULATION of the GABA RECEPTORS

Further to this, bear in mind that natural compounds, such as SKULLCAP comprise a combination of MANY subcomponent substances, and hence will not have a single physiological or pharmacological effect. As such, whist there is indeed evidence that some of the consistuents within SKULLCAP are SEROTONIN RECEPTOR AGONISTS, this does not in fact negate the fact that some or other consistuents within SKULLCAP function as BENZODIAZEPINE / GABA RECEPTOR AGONISTS and GABA REUPTAKE INHIBITORS; i.e. it appears that SKULLCAP's mechanism of action includes ALL THREE, namely BENZODIAZEPINE / GABA RECEPTOR AGONIST, GABA REUPTAKE INHIBITOR and SEROTONIN RECEPTOR AGONIST. I hope this helps clarify matters

Please kindly note that I am NOT implying that SKULLCAP is the 'spawn of the Devil' and should be avoided at all costs; I am simply stating that due to its mechanisms of action, which will to an extent induce down-relation of the GABA RECEPTORS with prolonged usage for the medium to long-term, usage of SKULLCAP should be limited to either occasional short-term use or simply CYCLED ON/OFF with the OFF period being sufficiently long to allow status to return to baseline. I.e. If you like the effects of SKULLCAP by all means carry on taking it; just be sure to take appropriate breaks from using it so as to avoid the potential for receptor down-regulation

Edited by ScienceGuy, 19 February 2012 - 12:52 PM.

[Ark]

An in vivo behavioural test measuring the anxiolytic responses in rats administered aqueous extracts of skullcap showed a significant difference between treated and control rats (n=21, p<0.05) (17).
In vitro aqueous extracts of skullcap induced release of [3H] GABA in rat brain synaptosomes. Inhibition of GABA reuptake in cells explains the in vivo mechanism by which skullcap has an inhibitory effect on neurotransmission (17).
In vitro studies with baicalin and the aglycone baicalein from Scutellaria baicalensis demonstrate binding with high affinity to the benzodiazepine site of GABAA, contributing to the anxiolytic properties (17).

The discovery of relatively high quantities of serotonin in skullcap may explain the in vitro study, which found that skullcap extracts bind to the serotonin 5-HT7 receptor (8,18)
http://www.scu.edu.a...n/index.php/43/

Hey Ark,

I'm not quite sure what point you are trying to make here... But to clarify, there is conclusive substantiated evidence from MULTIPLE studies that some of the consistuents within SKULLCAP most certainly function as BENZODIAZEPINE / GABA RECEPTOR AGONISTS, and as such it would be advisable to CYCLE usage ON/OFF (or limit usage to occasional short-term usage only) to avoid the potential for RECEPTOR DOWN-REGULATION

Furthermore, the fact that there also exists consituents within SKULLCAP that function as GABA REUPTAKE INHIBITOR further compounds this situation since GABA REUPTAKE INHIBITORS will also induce DOWN-REGULATION of the GABA RECEPTORS

Further to this, bear in mind that natural compounds, such as SKULLCAP comprise a combination of MANY subcomponent substances, and hence will not have a single physiological or pharmacological effect. As such, whist there is indeed evidence that some of the consistuents within SKULLCAP are SEROTONIN RECEPTOR AGONISTS, this does not in fact negate the fact that some or other consistuents within SKULLCAP function as BENZODIAZEPINE / GABA RECEPTOR AGONISTS and GABA REUPTAKE INHIBITORS; i.e. it appears that SKULLCAP's mechanism of action includes ALL THREE, namely BENZODIAZEPINE / GABA RECEPTOR AGONIST, GABA REUPTAKE INHIBITOR and SEROTONIN RECEPTOR AGONIST. I hope this helps clarify matters

Please kindly note that I am NOT implying that SKULLCAP is the 'spawn of the Devil' and should be avoided at all costs; I am simply stating that due to its mechanisms of action, which will to an extent induce down-relation of the GABA RECEPTORS with prolonged usage for the medium to long-term, usage of SKULLCAP should be limited to either occasional short-term use or simply CYCLED ON/OFF with the OFF period being sufficiently long to allow status to return to baseline. I.e. If you like the effects of SKULLCAP by all means carry on taking it; just be sure to take appropriate breaks from using it so as to avoid the potential for receptor down-regulation

O hey ScienceGuy, i just wanted to know what you thought about the extra information i had found.

Thanks for your reply.

Ark

[Ark]

An in vivo behavioural test measuring the anxiolytic responses in rats administered aqueous extracts of skullcap showed a significant difference between treated and control rats (n=21, p<0.05) (17).
In vitro aqueous extracts of skullcap induced release of [3H] GABA in rat brain synaptosomes. Inhibition of GABA reuptake in cells explains the in vivo mechanism by which skullcap has an inhibitory effect on neurotransmission (17).
In vitro studies with baicalin and the aglycone baicalein from Scutellaria baicalensis demonstrate binding with high affinity to the benzodiazepine site of GABAA, contributing to the anxiolytic properties (17).

The discovery of relatively high quantities of serotonin in skullcap may explain the in vitro study, which found that skullcap extracts bind to the serotonin 5-HT7 receptor (8,18)
http://www.scu.edu.a...n/index.php/43/

Hey Ark,

I'm not quite sure what point you are trying to make here... But to clarify, there is conclusive substantiated evidence from MULTIPLE studies that some of the consistuents within SKULLCAP most certainly function as BENZODIAZEPINE / GABA RECEPTOR AGONISTS, and as such it would be advisable to CYCLE usage ON/OFF (or limit usage to occasional short-term usage only) to avoid the potential for RECEPTOR DOWN-REGULATION

Furthermore, the fact that there also exists consituents within SKULLCAP that function as GABA REUPTAKE INHIBITOR further compounds this situation since GABA REUPTAKE INHIBITORS will also induce DOWN-REGULATION of the GABA RECEPTORS

Further to this, bear in mind that natural compounds, such as SKULLCAP comprise a combination of MANY subcomponent substances, and hence will not have a single physiological or pharmacological effect. As such, whist there is indeed evidence that some of the consistuents within SKULLCAP are SEROTONIN RECEPTOR AGONISTS, this does not in fact negate the fact that some or other consistuents within SKULLCAP function as BENZODIAZEPINE / GABA RECEPTOR AGONISTS and GABA REUPTAKE INHIBITORS; i.e. it appears that SKULLCAP's mechanism of action includes ALL THREE, namely BENZODIAZEPINE / GABA RECEPTOR AGONIST, GABA REUPTAKE INHIBITOR and SEROTONIN RECEPTOR AGONIST. I hope this helps clarify matters

Please kindly note that I am NOT implying that SKULLCAP is the 'spawn of the Devil' and should be avoided at all costs; I am simply stating that due to its mechanisms of action, which will to an extent induce down-relation of the GABA RECEPTORS with prolonged usage for the medium to long-term, usage of SKULLCAP should be limited to either occasional short-term use or simply CYCLED ON/OFF with the OFF period being sufficiently long to allow status to return to baseline. I.e. If you like the effects of SKULLCAP by all means carry on taking it; just be sure to take appropriate breaks from using it so as to avoid the potential for receptor down-regulation

O hey ScienceGuy, i just wanted to know what you thought about the extra information i had found.

Thanks for your reply.

Ark

[ScienceGuy]

O hey ScienceGuy, i just wanted to know what you thought about the extra information i had found.

Thanks for your reply.

Ark

Glad to help

I think you're very much onto something regards the whole PREP INHIBITION concept

I would be great to discover a compound that is a SELECTIVE PREP INHIBITOR

[Lufega]

Ginkgo has some compounds that inhibit PE. This might finally explain how it improves memory. I think the dose is key. I didn't feel the cognitive enhancement of berberine until I used a gram or so per day.

Prolyl endopeptidase inhibitors from the leaves of Ginkgo biloba.

Lee JH, Lee SY, Lee KS, Jang HJ, Lee KH, Hahn TR, Paik YS.

Source

College of Environment and Applied Chemistry, Kyung Hee University, Suwon, Korea.

Abstract

Prolyl endopeptidase (PEP, EC 3.4.21.26) hydrolyzes proline-containing neuropeptides, such as vasopressin, substance P, and thyrotropin-releasing hormone (TRH), and is suggested to participate in learning and memory processes. Ginkgo biloba leaves, upon examination for anti-amnestic constituents as new types of PEP inhibitors, showed significant PEP inhibition. PEP activity-guided fractionation and column chromatography of the MeOH extracts of G. biloba leaves resulted in the isolation of 6-(8'Z-pentadecenyl)salicylic acid (1) and 6-(10'Z-heptadecenyl)salicylic acid (2). The kinetic study indicated that compounds 1 and 2 are non-competitive inhibitors of prolyl endopeptidase with Ki values of 0.87 and 0.80 microM, respectively. PMID:15643562 [PubMed - indexed for MEDLINE]

[Ampa-omega]

hey check this out:
http://en.wikipedia.org/wiki/S-17092

S-17092 is a drug which acts as a selective inhibitor of the enzyme Prolyl endopeptidase.[1] This enzyme is involved in the metabolic breakdown of a number of neuropeptide neurotransmitters in the brain,[2][3] and so inhibiting the action of the enzyme increases the activity of these neuropeptides. This produces nootropic effects which make S-17092 a promising and novel treatment for neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease.[4][5]

[Metagene]

Just chumming the waters.

 

The Potential of Prolyl Oligopeptidase as a drug target.

 

 

http://PREPepublicat...2-61-0671-7.pdf

[Lufega]

I've been experimentimg with PE Inhibitors for sometime and its one of the few things i respond to very well for improving my memory.

Most of the popular ones come with unwanted effects. I lose a noticeable amount of muscle mass and tendon strength on berberine and not all formulas work. Only berberine in tribiotics works for me. The rest do nill. I figured out it's because the artemisinin increases the absorption of berberine.

Next i tried baicalein in chinese skullcap but that a strong sedative effect.

I googled some more and found a proprietary formula combining blueberry, strawberry and spinach is also a pe inhibitor.

http://www.ncbi.nlm....ubmed/22871089/

I found it in a formula called cognimag but its almost 60 bucks to try it out.

Anyone have any experience with it ?