27 votes
Posted 07 January 2014 - 03:10 AM
Posted 07 January 2014 - 03:23 AM
Which form would be the most potent and useable?
If we believe the inkanatural website, the fruits have the most essential oils (5%) versus the leaf (2%), can't say for the bark. For ease of administration, wouldn't be the oil extract be easier to control in regards to quantity?
For all we know, the leaf extract from Healing Herbs might be a big pot of leafs.
Abstract
Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.
Edited by abelard lindsay, 07 January 2014 - 03:40 AM.
Posted 07 January 2014 - 04:31 AM
http://www.ncbi.nlm.nih.gov/pubmed/19815045Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator. Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin. Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators. Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter. Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity.
Posted 07 January 2014 - 11:45 AM
http://www.ncbi.nlm.nih.gov/pubmed/15671126(...)After dopamine D2 receptor blockade, performance was not impaired on the spatial WM (SWM) task, but was impaired on the auditory counting task with distraction. Sulpiride did not impair, but rather appeared to enhance trial-and-error learning overall. Thus, we were unable to support the notion that dopaminergic modulation preferentially influences spatial over non-spatial processing during learning. In addition, recognition was impaired in the emotional memory task after encoding on drug compared to placebo.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312696/Neurospheres have been demonstrated to express D1- and D2-like DAergic receptors.[143–145] Treatment of neurospheres with bromocriptine and apomorphine, significantly increased cell proliferation[143,144] which was blocked by the D2-like antagonist sulpiride,[143,144] suggesting that it was indeed mediated via the D2-like receptors.
Posted 07 January 2014 - 01:50 PM
Myself, I'm going to see if Forskolin's effect can be replicated by CORDYCEPS.
Studies suggest it's also an agonist at adenosine receptors (A2), while having other cool properties.
http://www.ncbi.nlm......7229422<br />http://www.ncbi.nlm......1512251<br />whereas the NO-sensitive guanylyl cyclase inhibitor ODQ did not alter the cordycepin-induced up-regulation of cGMP, the adenylyl cyclase inhibitor SQ22536 completely blocked the cAMP enhancement mediated by cordycepin, indicating that cordycepin had different modes of action.
But I'm still testing Cordyceps + Artichoke out of curiosity. At least, it'll probably have some cool effects on fertility.
http://www.jbc.org/content/285/4/2610.full3′-Deoxyadenosine, also known as cordycepin, is a known polyadenylation inhibitor with a large spectrum of biological activities, including anti-proliferative, pro-apoptotic and anti-inflammatory effects. In this study we confirm that cordycepin reduces the length of poly(A) tails, with some mRNAs being much more sensitive than others. The low doses of cordycepin that cause poly(A) changes also reduce the proliferation of NIH3T3 fibroblasts. At higher doses of the drug we observed inhibition of cell attachment and a reduction of focal adhesions. Furthermore, we observed a strong inhibition of total protein synthesis that correlates with an inhibition of mammalian target of rapamycin (mTOR) signaling, as observed by reductions in Akt kinase and 4E-binding protein (4EBP) phosphorylation. In 4EBP knock-out cells, the effect of cordycepin on translation is strongly reduced, confirming the role of this modification. In addition, the AMP-activated kinase (AMPK) was shown to be activated. Inhibition of AMPK prevented translation repression by cordycepin and abolished 4EBP1 dephosphorylation, indicating that the effect of cordycepin on mTOR signaling and protein synthesis is mediated by AMPK activation. We conclude that many of the reported biological effects of cordycepin are likely to be due to its effects on mTOR and AMPK signaling.
Edited by Jeoshua, 07 January 2014 - 02:49 PM.
Posted 08 January 2014 - 05:46 AM
Posted 08 January 2014 - 03:45 PM
Etazolate is a PDE4 inhibitor that increases cAMP levels by inhibiting the breakdown of endogenously produced cAMP. Iontophoretic application of etazolate (25 nA) had highly consistent suppressing effects on spatial mnemonic activity in 10 of 12 PFC neurons.
Recent studies indicate that elevated cAMP signaling in PFC impairs behavioral measures of WM, and that α2A-AR stimulation improves WM performance via Gi suppression of cAMP intracellular signaling. In contrast to long-term memory consolidation which is facilitated by cAMP signaling, WM performance at short delays is impaired by increased cAMP signaling, e.g., following infusion of the cAMP analog, Sp-cAMPS, into the rat PFC (Taylor et al., 1999). Similarly, WM performance of aged monkeys is impaired by systemic administration of the phosphodiesterase 4 (PDE4) inhibitor, rolipram, which increases endogenous levels of cAMP (Ramos et al., 2003). The enhancing effects of guanfacine on WM can be blocked by coinfusion of low dose Sp-cAMPS in the rat PFC (Ramos et al., 2006). Conversely, inhibition of cAMP with Rp-cAMPS infusions improved WM performance (Ramos et al., 2003). These findings indicate that excessive cAMP actions in PFC impair WM. Importantly, dysregulated cAMP signaling may contribute to WM deficits in schizophrenia, as a gene linked to this disorder, DISC1, has been found to upregulate PDE4B activity under conditions of high cAMP production (Millar et al., 2005). Thus it is key to understand how elevated cAMP signaling impairs PFC cognitive operations.
Edited by chung_pao, 08 January 2014 - 03:49 PM.
Posted 08 January 2014 - 04:15 PM
So d2 antagonism at least inhibits cell proliferation. And I am pretty sure that is not because of the specific drug, but because of its antagonistic action on d2. Decreased neurogenesis(or even potential atrophy) in some parts of the brain is a huge price to pay for better learning capabilities while on a stack.
!
Posted 08 January 2014 - 05:28 PM
This study explains the problem with the mechanism of ciltep: reduced working memory.
This affects speech, executive function and spatial senses.
http://www.sciencedi...092867407003443Etazolate is a PDE4 inhibitor that increases cAMP levels by inhibiting the breakdown of endogenously produced cAMP. Iontophoretic application of etazolate (25 nA) had highly consistent suppressing effects on spatial mnemonic activity in 10 of 12 PFC neurons.
Recent studies indicate that elevated cAMP signaling in PFC impairs behavioral measures of WM, and that a2A-AR stimulation improves WM performance via Gi suppression of cAMP intracellular signaling. In contrast to long-term memory consolidation which is facilitated by cAMP signaling, WM performance at short delays is impaired by increased cAMP signaling, e.g., following infusion of the cAMP analog, Sp-cAMPS, into the rat PFC (Taylor et al., 1999). Similarly, WM performance of aged monkeys is impaired by systemic administration of the phosphodiesterase 4 (PDE4) inhibitor, rolipram, which increases endogenous levels of cAMP (Ramos et al., 2003). The enhancing effects of guanfacine on WM can be blocked by coinfusion of low dose Sp-cAMPS in the rat PFC (Ramos et al., 2006). Conversely, inhibition of cAMP with Rp-cAMPS infusions improved WM performance (Ramos et al., 2003). These findings indicate that excessive cAMP actions in PFC impair WM. Importantly, dysregulated cAMP signaling may contribute to WM deficits in schizophrenia, as a gene linked to this disorder, DISC1, has been found to upregulate PDE4B activity under conditions of high cAMP production (Millar et al., 2005). Thus it is key to understand how elevated cAMP signaling impairs PFC cognitive operations.
Now if we could only avoid cAMP accumulation in the PFC, that'd be great. But would also require very selective PDE inhibition. (?)
Posted 08 January 2014 - 07:19 PM
So d2 antagonism at least inhibits cell proliferation. And I am pretty sure that is not because of the specific drug, but because of its antagonistic action on d2. Decreased neurogenesis(or even potential atrophy) in some parts of the brain is a huge price to pay for better learning capabilities while on a stack.
Food for thoughts : Could the neurogenesis coming from a dose of uridine/DHA MrHappy stack, taken before going bed, help to mitigate the side effects of d2 antagonism ?
Just saying, i'm waay out of my league here
I would not go into the d2 antagonism direction in the first place. And, it is still unclear to me why uridine and forskolin do not play well with each other. A dopamine depleting effect has been proposed, but I am not sure if this is the (only) reason.Quercetin and quercetin 3′-sulphate inhibited endothelin and U46619-induced contractions with greater potency (three- to fivefold) against the former, while quercetin 3-glucoronide was inactive. Quercetin enhanced both the cyclic GMP content of the artery (threefold) and cyclic GMP-dependent relaxations to GTN and SNP (two to threefold), but forskolin-induced relaxations were unaffected. Although the effect of quercetin was qualitatively similar to that noted for UK-114,542, a selective inhibitor of phosphodiesterase 5, it was still evident against SNP-induced relaxations in the presence of 10 nM UK-114,542. Quercetin and quercetin 3′-sulphate significantly reduced the development of GTN-associated ‘tolerance’.
Posted 08 January 2014 - 11:18 PM
It seems you edited your post in the meantime, but anyways a question: a google search does show that both modafinil and caffeine either slow down degradation or increase levels of cAMP, meaning that they should impair WM, which seem counter-intuitive to me... I'm not addicted nor have tolerance to either of them but when I take them I really have razor sharp focus and am VERY productive. It might be related to motivation, but I feel that I solve problems much more easily while on them.This is interesting, seeing as drugs like caffeine and modafinil do the opposite.
This is also evident on forums, as modafinil usually produces "wall of texts"-long posts, while CILTEP-posts are more succinct.
Edited by rikelme, 08 January 2014 - 11:22 PM.
Posted 09 January 2014 - 04:34 AM
For anyone trying to increase cGMP... quercetin has an effect on it too, I haven't looked into it so I can't say its good or bad, just pasting it here FYI:
http://www.ncbi.nlm....les/PMC2828021/Quercetin and quercetin 3′-sulphate inhibited endothelin and U46619-induced contractions with greater potency (three- to fivefold) against the former, while quercetin 3-glucoronide was inactive. Quercetin enhanced both the cyclic GMP content of the artery (threefold) and cyclic GMP-dependent relaxations to GTN and SNP (two to threefold), but forskolin-induced relaxations were unaffected. Although the effect of quercetin was qualitatively similar to that noted for UK-114,542, a selective inhibitor of phosphodiesterase 5, it was still evident against SNP-induced relaxations in the presence of 10 nM UK-114,542. Quercetin and quercetin 3′-sulphate significantly reduced the development of GTN-associated ‘tolerance’.
Proposed modulators of LTP; Modulator Targets
β-Adrenergic receptor; cAMP, MAPK amplification
Nitric oxide synthase; Guanylyl cyclase, PKG, NMDAR
Dopamine receptor; cAMP, MAPK amplification
Metabotropic glutamate receptor; PKC, MAPK amplification
As described previously, the molecules that underlie LTP can be classified as mediators or modulators. A mediator of LTP is a molecule, such as the NMDA receptor or calcium, whose presence and activity is necessary for generating LTP under nearly all conditions. By contrast, a modulator is a molecule that can alter LTP but is not essential for its generation or expression.
In addition to the signaling pathways described above, hippocampal LTP may be altered by a variety of modulators. For example, the steroid hormone estradiol may enhance LTP by driving CREB phosphorylation and subsequent dendritic spine growth. Additionally, β-adrenergic receptor agonists such as norepinephrine may alter the protein synthesis-dependent late phase of LTP. Nitric oxide synthase activity may also result in the subsequent activation of guanylyl cyclase and PKG. Similarly, activation of dopamine receptors may enhance LTP through the cAMP/PKA signaling pathway.
A google search does show that both modafinil and caffeine either slow down degradation or increase levels of cAMP, meaning that they should impair WM, which seem counter-intuitive to me...
http://www.sciencedi...006899387904252The adenosine triphosphate-dependent calcium uptake by endoplasmic reticulum elements of lysed synaptosomes from rat brain cortex was studied. Caffeine exhibited a biphasic effect on this calcium uptake activity: concentrations of 1, 2, 5, 10 or 30 mM caffeine stimulated calcium uptake by 62, 111, 73, 88 and 60% respectively, whereas calcium uptake was inhibited by 55% at a 60-mM concentration of caffeine. Calcium release from endoplasmic reticulum elements of lysed brain synaptosomes was stimulated by 10 mM caffeine. Cyclic adenosine 3′,5′-monophosphate stimulated calcium uptake in the lysed synaptosome preparation: exogenous concentrations of 0.05, 0.5, 5, 50 of 500 μM stimulated uptake by 67, 67, 95, 38 or 67% respectively. To explore the possibility that caffeine stimulated calcium uptake through inhibition of phosphodiesterase and consequent preservation of cyclic adenosine 3′,5′-monophosphate, we have tested whether caffeine retained its ability to stimulate calcium uptake under conditions of maximal stimulation by cyclic adenosine 3′,5′-monophosphate. The combined presence of 10 mM caffeine and 5 μM cyclic adenosine 3′,5′-monophosphate resulted in an approximate doubling of the calcium uptake as compared to the uptake in the presence of the cyclic nucleotide alone, indicating that the stimulation due to caffeine does not occur via cyclic adenosine 3′,5′-monophosphate.
Edited by Jeoshua, 09 January 2014 - 05:15 AM.
Posted 09 January 2014 - 04:35 PM
I know it sounds pretty far-fetched - the last quote isn't even a study.
But I'm still testing Cordyceps + Artichoke out of curiosity. At least, it'll probably have some cool effects on fertility.
In addition, I found Artichoke had much stronger effects when combined with EGCG.
Turns out, the concentration of Luteolin is increased by COMT-inhibitors (such as egcg), because COMT metabolizes Luteolin.
It's a very strong difference, and using 900 mg artichoke extract with egcg definitely makes the stack too strong.
http://www.ncbi.nlm....pubmed/23386290
[Luteolin was a rare substrate of human COMT favoring a para-methylation, but further demethylation by human CYP1A2 and CYP3A4/5 caused a preference of accumulation in meta-methylated luteolin in vivo.
Posted 09 January 2014 - 09:02 PM
That would be me! And I thought nobody reads MY posts!
So honestly with the CILTEP stack, as it stands, there are a few issues. Some of the substances used are Armoatase inhibitors, which would decrease estradiol levels, leading to less dendritic spine growth and phosphorylation. For this reason I suggest finding something other than Forskolin, for the increasing of cAMP.
For both of these reasons, and at the suggestion of a previous post, I was looking into Cordycepin. It does have the property of potentially inhibiting late-phase LTP by inhibiting long chain DNA and RNA synthesis, but that is only at very high levels, in vitro, and there is no real evidence that I could find that it had ever been tested in that sense in vivo. There is also the interesting property of Cordycepin, being very close in structure to Adenosine, to actually be phoshoporylated and become something akin to cyclic Cordycepin Monophosphate. The molecule's physical structure (a kind of deoxyadenosine) allows it, and its properties should be close enough to cAMP to allow it to be used by the cell in the same way, yet far enough away from cAMP to be harder to break down.
Cordycepin also seems to increase Free Testosterone levels in a way that does not involve Aromatase inhibition, so that is also a plus.
----------------------------------A google search does show that both modafinil and caffeine either slow down degradation or increase levels of cAMP, meaning that they should impair WM, which seem counter-intuitive to me...
Endogenous chemicals can be increased in a few different ways: by increasing their production, by inhibiting their breakdown, on by inhibiting their function in the case of chemicals which change upon being used up (like ATP). There is also the difference between intracellular amounts of chemicals and extracellular amounts.
If you antagonize dopamine receptors, for example, you will increase the extracellular levels of dopamine while not activating the receptor, basically by plugging up the hole. The intracellular levels of dopamine, in the receptor part of the neuron, will not likewise be increased. On the other hand, if you supplement L-Tyrosine or L-Dopa, you can increase the amount of intracellular AND extracellular dopamine without changing how it functions in the brain on a basic level.
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As far as the effects of caffeine on this stack:
It seems that in addition to its PDE inhibition, it also increases the Ca+ metabolism, which is a bit part of LTP. It also has effects on the β-Adrenergic receptor. It also does all of this completely separately in it's method of effect from cAMP. I would almost say that Caffeine, or some other kind of Methylxanthine, should be considered as a canonical part of CILTEP's LTP Chemical Induction.
Posted 09 January 2014 - 10:04 PM
Are you suggesting that decreasing one's estradiol level is not a positive? I was under the impression that an aromatase inhibitor is a positive, so that we reduce the tendency for testosterone to be converted into excess estradiol. This is the first I've heard that lowering estradiol would reduce something we want, like dendritic spine growth. Is this a matter of estradiol being decreased below an optimal level, whereas the usual discussion relates to estradiol being decreased from an excess level caused by an artificially-increased testosterone level?
http://www.ncbi.nlm....pubmed/20928832Estrogens regulate dendritic spine density, but the mechanism and significance of this effect for brain networks remain unknown. We used repetitive imaging over several days to investigate how 17β-estradiol affected the turnover and long-term behavior of dendritic spines in CA1 cells of hippocampal slice cultures. We find that 17β-estradiol and serum in the culture medium tightly regulated spine density by promoting an increase in the rate of new spine formation and their transformation into synapses, without affecting spine elimination or stability. New spines formed during a transient 17β-estradiol application were preferentially eliminated upon removal of the hormone, in contrast with pre-existing spines that remained unaffected. Our results reveal that 17β-estradiol transiently regulates the complexity of hippocampal circuits without causing major alterations of pre-existing networks.
http://www.ncbi.nlm....pubmed/22699893Inhibitors of aromatase, the final enzyme of estradiol synthesis, are suspected of inducing memory deficits in women. In previous experiments, we found hippocampal spine synapse loss in female mice that had been treated with letrozole, a potent aromatase inhibitor. In this study, we therefore focused on the effects of letrozole on long-term potentiation (LTP), which is an electrophysiological parameter of memory and is known to induce spines, and on phosphorylation of cofilin, which stabilizes the spine cytoskeleton and is required for LTP in mice. In acute slices of letrozole-treated female mice with reduced estradiol serum concentrations, impairment of LTP started as early as after 6 h of treatment and progressed further, together with dephosphorylation of cofilin in the same slices. Theta-burst stimulation failed to induce LTP after 1 week of treatment. Impairment of LTP was followed by spine and spine synapse loss. The effects were confirmed in vitro by using hippocampal slice cultures of female mice. The sequence of effects in response to letrozole were similar in ovariectomized female and male mice, with, however, differences as to the degree of downregulation. Our data strongly suggest that impairment of LTP, followed by loss of mushroom spines and spine synapses in females, may have implications for memory deficits in women treated with letrozole.
http://www.ncbi.nlm....pubmed/22198873Neurosteroids are synthesized de novo from cholesterol in the brain. In rodents, the Purkinje cell actively produces several kinds of neurosteroids including estradiol during neonatal life, when cerebellar neuronal circuit formation occurs. Estradiol may be involved in cerebellar neuronal circuit formation through promoting neuronal growth and synaptic contact, because the Purkinje cell expresses estrogen receptor-β. To test this hypothesis, in this study we examined the effect of estradiol on dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell using neonatal wild-type (WT) mice or cytochrome P450 aromatase knock-out (ArKO) mice. Administration of estradiol to neonatal WT or ArKO mice increased dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell. In contrast, WT mice treated with tamoxifen, an ER antagonist, or ArKO mice exhibited decreased Purkinje dendritic growth, spinogenesis, and synaptogenesis at the same neonatal period. Estrogen administration to neonatal WT or ArKO mice increased the expression of brain-derived neurotrophic factor (BDNF) in the cerebellum, whereas tamoxifen decreased the BDNF level in WT mice similar to ArKO mice. BDNF administration to tamoxifen-treated WT mice increased Purkinje dendritic growth. These results indicate that estradiol induces dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell via BDNF action during neonatal life.
http://www.biolrepro.../70/5/1358.longThere is increasing evidence that 17β-estradiol (E2) directly influences the quality of maturing oocytes and thus the outcome of assisted reproduction treatment. Although Cordyceps sinensis (CS) mycelium, a Chinese herbal medicine, is believed to enhance libido and fertility in both sexes, the mechanism of its effect in women has not been determined. The aim of the present study was to evaluate the effects of CS on steroidogenic enzyme expression and E2 biosynthesis in human granulosa-lutein cells (GLC). We found that CS induced E2 production by GLC in a dose- and time-dependent manner and that a 3-h treatment with CS induced increased levels of mRNAs coding for the P450 side chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase. Western blot analysis demonstrated that, after treatment with CS for 3 h, protein levels of steroidogenic acute regulatory protein (StAR) and aromatase were upregulated while P450scc and 3β-HSD levels showed no substantial change. New protein synthesis was required for CS-induced E2 production because it was abrogated by cycloheximide pretreatment. Addition of 22®-hydroxycholesterol, thus bypassing the need for StAR protein, did not induce as much E2 production as CS treatment, indicating that upregulation of StAR protein was not the only factor contributing to CS-induced steroidogenesis. Cotreatment of GLCs with CS and aminoglutethimide, an aromatase inhibitor, completely abolished CS-induced E2 production. In conclusion, treatment of GLCs with CS results in increased E2 production due, at least in part, to increased StAR and aromatase expression. These data may help in the development of treatment regimens to improve the success rate of in vitro fertilization.
http://www.ncbi.nlm....pubmed/17229422Cordycepin (3'-deoxyadenosine) is isolated from Cordyceps militaris, a species of the fungal genus Cordyceps. Cordycepin is an ingredient used in traditional Chinese medicine and is prescribed for various diseases, such as cancer and chronic inflammation. In this study, we investigated the novel effect of cordycepin (3'-deoxyadenosine) on collagen-induced human platelet aggregation. Cordycepin inhibited dose-dependently collagen-induced platelet aggregation in the presence of various concentrations of exogenous CaCl(2). Of two aggregation-inducing molecules, cytosolic free Ca(2+) ([Ca(2+)](i)) and thromboxane A(2) (TXA(2)), cordycepin (500 microM) blocked the up-regulation of [Ca(2+)](i), by up to 74%, but suppressed TXA(2) production by 46%. Subsequently, Ca(2+)-dependent phosphorylation of both 47-kDa and 20-kDa proteins in collagen-treated platelets was potently diminished by cordycepin. However, upstream pathways for producing these two inducers, such as the activation of phospholipase C-gamma2 (PLC-gamma2) (assessed by the phosphotyrosine level) and the formation of inositol 1,4,5-trisphosphate (IP(3)), were not altered by cordycepin. Cordycepin increased the level of second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in collagen-stimulated platelets. Whereas the NO-sensitive guanylyl cyclase inhibitor ODQ did not alter the cordycepin-induced up-regulation of cGMP, the adenylyl cyclase inhibitor SQ22536 completely blocked the cAMP enhancement mediated by cordycepin, indicating that cordycepin had different modes of action. Therefore, our data suggest that the inhibitory effect of cordycepin on platelet aggregation might be associated with the down-regulation of [Ca(2+)](i) and the elevation of cAMP/cGMP production.
http://www.ncbi.nlm....pubmed/11712663The stimulatory effect of Cordyceps sinensis (CS) on MA-10 mouse Leydig tumor cell steroidogenesis was previously demonstrated in our laboratory. In the present studies, we further determined the effect of CS on steroidogenesis in purified normal mouse Leydig cells. Different concentrations of CS (0.1-10 mg/ml) were added to Leydig cells without or with human chorionic gonadotropin (hCG) (50 ng/ml), and the steroid production was determined by radioimmunoassay (RIA). The results illustrated that CS stimulated normal mouse Leydig cell steroidogenesis in a dose-dependent relationship. CS at 3 mg/ml significantly stimulated testosterone production (p<0.05). Concerning the temporal relationship, CS at 3 mg/ml stimulated maximal testosterone production between 2 to 3 hr. Interestingly, hCG-stimulated testosterone productions were suppressed by CS in a dose-dependent relationship. CS also reduced dbcAMP-stimulated testosterone productions, which indicated that CS affected signal transduction pathway of steroidogenesis after the formation of cyclic AMP. Moreover, cycloheximide inhibited CS-treated mouse Leydig cell testosterone production, suggesting that new protein synthesis was required for CS-stimulated steroidogenesis.
http://www.ncbi.nlm.nih.gov/pubmed/24286368Cordycepin is a bioactive component of the fungus Cordyceps militaris. Previously, we showed that cordycepin can alleviate hyperlipidemia through enhancing the phosphorylation of AMP-activated protein kinase (AMPK), but the mechanism of this stimulation is unknown. Here, we investigated the potential mechanisms of cordycepin-induced AMPK activation in HepG2 cells. Treatment with cordycepin largely reduced oleic acid (OA)-elicited intracellular lipid accumulation and increased AMPK activity in a dose-dependent manner. Cordycepin-induced AMPK activation was not accompanied by changes in either the intracellular levels of AMP or the AMP/ATP ratio, nor was it influenced by calmodulin-dependent protein kinase kinase (CaMKK) inhibition; however, this activation was significantly suppressed by liver kinase B1 (LKB1) knockdown. Molecular docking, fluorescent and circular dichroism measurements showed that cordycepin interacted with the γ1 subunit of AMPK. Knockdown of AMPKγ1 by siRNA substantially abolished the effects of cordycepin on AMPK activation and lipid regulation. The modulating effects of cordycepin on the mRNA levels of key lipid regulatory genes were also largely reversed when AMPKγ1 expression was inhibited. Together, these data suggest that cordycepin may inhibit intracellular lipid accumulation through activation of AMPK via interaction with the γ1 subunit.
Re: your statement that L-Tyrosine increases the amount of intracellular AND extracellular dopamine without changing how it functions in the brain. Would that hold true if supplementing with N-Acetyl-L-Tyrosine?
I'm unsure how to interpret your use of the word canonical in your final sentence. Are you saying that caffeine should be considered an essential part of the CILTEP stack?
Edited by Jeoshua, 09 January 2014 - 10:54 PM.
Posted 09 January 2014 - 11:06 PM
I'm unsure how to interpret your use of the word canonical in your final sentence. Are you saying that caffeine should be considered an essential part of the CILTEP stack?
Yes. As in "In the Canon", when refering to an accepted fact within a particular work of fiction, and not just a fan theory. Or, alternatively, as the Catholics would see it as meaning "straight from The Book". And I officially denounce and object to any conflation and discussion comparing the "work of fiction" and "Catholic" angles, for the record
The effects of Caffeine (and by extension, other Methylxanthines) are too good to pass up as just a possible adjunct to the stack, in my experience. They synergize so well with the cAMP and potential cGMP, Ca+, and β-Adrenergic effects that early-phase LTP induction relies upon, and their normal methodology of usage, being in drink or food form (coffee, hot cocoa, tea), give a natural tool by which one can modulate the specific intensities of the effects in play, extend the length of their effects, and allow one to fight off the effects of withdrawl once the half-lives of the other chemicals in effect wear off.
Personally I have been using Theobromine, which is potentially less stimulating, and therefore a bit more useful for me, in the form of:As another benefit, Cocoa also contains non-trivial amounts of L-Tyrosine and L-Phenylalanine, which also are potential adjuncts to the stack. I down the rest of the stack in pill form, washing it down with this Cocoa mix, and sip on the remainder for the next few hours. I have noticed no crashes, no late-day drowsiness, and it's really fucking tasty, to boot.
- Raw Cocoa powder fortified with Chocamine (40+ mg Theobromine per 8 fl oz, 20 mg Caffeine, 20 mg Theophylline)
- Lightly salted (Himalayan Pink Salt) and lightly sugared (Just the white shit, until I determine if Glucose would be more suitable)
- A dropper-full of Green Tea extract (EGCG delays the breakdown of Luteolin, also L-Theanine and more Methylxanthines)
- A gram of Creatine Monohydrate (Protects ATP transport, which is a possible benefit to the stack, as well)
- A tablespoon of Coconut Cream (MCTs, Polyunsaturated Fats, and it gives a nice color and mouth-feel)
- In 24 oz piping hot, filtered water
- Topped with a pinch of Ceylon Cinnamon (This is just for taste, not for any specific effects of Cinnamon)
But of course, I digress. Honestly, this drink has such specific and special effects, it could almost warrant it's own thread discussing them. It is a kind of stack, on its own. But, I have tried the CILTEP stack with, and without, this drink in the mix, and it definitely works in a very similar direction, and the effects synergize very strongly.
Posted 10 January 2014 - 03:13 AM
Could the NaturalStacks CILTEP formulation be depleting something that dark chocolate provides. The formulation contains L-Phenylalanine, so unless it doesn't include enough, would it be reasonable to rule that out?
Could it be L-Tyrosine? Could it be something that caffeine boosts?
http://www.ncbi.nlm....pubmed/19815045Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator. Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin. Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators. Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter. Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity.
Edited by Jeoshua, 10 January 2014 - 04:00 AM.
Posted 10 January 2014 - 03:38 AM
. I've been experimenting on my own and come across some dead ends, any thoughts would be appreciated thanks 
.
Edited by bzyb, 10 January 2014 - 04:04 AM.
Posted 10 January 2014 - 05:12 AM
Also, Luteolin is a PDE 1-5 inhibitor (Affinities being for 4, 2, 1, 3, and 5, in that order, descending), so we are basically halfway there in having a cAMP/cGMP increaser with Cordyceps + Luteolin.
PDE3 is a dual-substrate phosphodiesterase responsible for hydrolyzing both cAMP and cGMP whilst being simultaneously inhibited by cGMP.
HEL cells grown for 24 h in the presence of 50 microM forskolin, an adenylate cyclase activator, demonstrate further increase in PDE3A of 274% of control (p = 0.03).
Edited by abelard lindsay, 10 January 2014 - 05:40 AM.
Posted 10 January 2014 - 06:30 AM
http://www.ncbi.nlm....pubmed/10454367First, brief perfusion with 8-Br-cGMP before weak tetanic stimulation produced long-lasting potentiation in the CA1 region of hippocampal slices, but more prolonged perfusion with 8-Br-cGMP before the tetanus did not produce long-lasting potentiation. Second, the activity-dependent long-lasting potentiation by cGMP analogs was reduced when NMDA receptors were completely blocked, indicating that NMDA receptor activation contributes to, but is not required for, the potentiation. The amount of reduction of the potentiation differed with different protocols, and in some cases could be complete. Third, LTP produced by strong tetanic stimulation in the stratum radiatum of CA1 (which expresses eNOS) was blocked by inhibitors of soluble guanylyl cyclase or cGMP-dependent protein kinase, but LTP in the stratum oriens (which does not express eNOS) was not.
http://www.ncbi.nlm....pubmed/17229422NO-sensitive guanylyl cyclase inhibitor ODQ did not alter the cordycepin-induced up-regulation of cGMP, the adenylyl cyclase inhibitor SQ22536 completely blocked the cAMP enhancement mediated by cordycepin, indicating that cordycepin had different modes of action. Therefore, our data suggest that the inhibitory effect of cordycepin on platelet aggregation might be associated with the down-regulation of [Ca(2+)](i) and the elevation of cAMP/cGMP production
...while fasting.
Edited by Jeoshua, 10 January 2014 - 06:59 AM.
Posted 10 January 2014 - 03:04 PM
Caffeine potently inhibited forskolin-stimulated cyclic AMP accumulation in slices of rat cerebral cortex, with an IC50 of 21 +/- 3 microM.
Edited by chung_pao, 10 January 2014 - 03:10 PM.
Posted 10 January 2014 - 04:32 PM
Posted 10 January 2014 - 07:28 PM
If you're not convinced of Abelard's point that you either focus on cAMP or cGMP, try upping your theobromine intake.
Artichoke extract and Yerba maté tea, for example, turns my awesome CILTEP-focus into a Nitric Oxide-haze of boners and erotic daydreams.
A note on the experience with CORDYCEPS: it wasn't very successful. It was short in duration and low in intensity, with a noticeable crash after 3.5 hours.
I suspect it had some cool effects on hormones though, as I became very hungry.
It didn't synergize with Forskolin and artichoke either.
In short: It was not a step up and Forskolin + Artichoke remains superior.
Posted 10 January 2014 - 07:53 PM
If you're not convinced of Abelard's point that you either focus on cAMP or cGMP, try upping your theobromine intake.
Artichoke extract and Yerba maté tea, for example, turns my awesome CILTEP-focus into a Nitric Oxide-haze of boners and erotic daydreams.
In short: It was not a step up and Forskolin + Artichoke remains superior.
Also a note on caffeine: If taken together with forskolin, this inhibits cAMP accumulation in the brain and causes drowsiness instead of the desired effect.
Caffeine can be taken after Forskolin and Artichoke though, when cAMP-levels have already increased from Forskolin.
http://www.ncbi.nlm..../pubmed/2172772Caffeine potently inhibited forskolin-stimulated cyclic AMP accumulation in slices of rat cerebral cortex, with an IC50 of 21 +/- 3 microM.
Posted 10 January 2014 - 09:17 PM
.
Posted 10 January 2014 - 11:09 PM
Hi there,
Anyone also experianced constipation withs restults in hemorrhoids :(
I have been taken for PDE-4 Inhibition 2x artichoke from now with only whater.
after 25 min for increasing my camp cAMP: 4mg cbolic, 100phyn, 1cap b50 vit, caff 0,1 grams with whater.
After 30 minutes bread.
Can artichoke cause this? Or second part of the stack?
I'm not wanting to eat first beceause I think it will diminish the efect.
Anyone here eating with ciltep and having good results, what are you eating
I though maybe artichoke 2x with 2 eggs? and whater
en the rest of the stack with oat flakes and milk.
The thing is that 0,04 of forskoling wil be not prober digested with the oat an milk? I think.
Also how long will it take for PDE-4 Inhibition?
Posted 11 January 2014 - 03:44 AM
Download the Study: http://download.cell...67407003443.pdfThe current study found that brain cells in PFC contain ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN) that reside on dendritic spines, the tiny protrusions on neurons that are specialized for receiving information. These channels can open when they are exposed to cAMP (cyclic adenosine monophosphate). When open, the information can no longer flow into the cell, and thus the network is effectively disconnected.
The study also found alpha-2A adrenergic receptors near the channels that inhibit the production of cAMP and allow the information to pass through into the cell, connecting the network. These receptors are stimulated by a natural brain chemical norepinephrine or by medications like guanfacine.
"Guanfacine can strengthen the connectivity of these networks by keeping these channels closed, thus improving working memory and reducing distractibility," she said. "This is the first time we have observed the mechanism of action of a psychotropic medication in such depth, at the level of ion channels."
Arnsten said the excessive opening of HCN channels might underlie many lapses in higher cognitive function. Stress, for example, appears to flood PFC neurons with cAMP, which opens HCN channels, temporarily disconnects networks, and impairs higher cognitive abilities.
http://www.ncbi.nlm.nih.gov/pubmed/9030202Caffeine has been extensively used to study intracellular Ca2+ control and contraction-relaxation in cardiomyocytes. The effects of caffeine on intracellular free Mg2+ concentration, [Mg2+]i, were studied in isolated adult rat ventricular myocytes by fluorescent techniques using mag-fura-2. Basal [Mg2+]i was 0.62 +/- 0.02 mM, n = 54, in quiescent cells and 0.73 +/- 0.02 mM, n = 23, in electrically-stimulated adult rat ventricular myocytes. Caffeine, 20 mM, significantly decreased [Mg2+] in both quiescent (-0.17 +/- 0.01 mM) and electrically-stimulated (-0.16 +/- 0.01 mM) adult ventricular myocytes. Ryanodine, a blocker for Ca(2+)-release channels of the sarcoplasmic reticulum, did not have any effect on basal [Mg2+]i, 0.67 +/- 0.02 mM nor on caffeine-induced reduction in [Mg2+]i, -0.16 +/- 0.01 mM in quiescent cardiomyocytes or electrically-stimulated cells; 0.74 +/- 0.03 mM and -0.11 +/- 0.03 mM, respectively. Ruthenium red, an inhibitor of mitochondrial Ca2+ uptake, also failed to alter basal [Mg2+]i, or caffeine-induced reduction in [Mg2+], in either quiescent or electrically-stimulated cells. The effects of caffeine on [Mg2+]i, may be important in considering the use of this drug to study contraction/function studies in heart cells.
http://www.ncbi.nlm.nih.gov/pubmed/16846100Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.
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