LONGECITY

Study on Nootropic Mechanism of Clausenamide

Abstract

Clausenamide is a compound isolated from clausena lansium (lour) skells.

(±) 、 (+) and (-) clausenamide were synthesized firstly in our institute. In the previous study, Clausenamide was shown to improve consolidation of memory impaired by anoxia and 〓. In this study, one way of passive avoidance response such as step down and step through tests and water maze test were used for comparison of effects of (±) clausenamide、 (-) clausenamide and piracetam on learning and memory and memory impairment induced by anisodine and 〓 in adult mice. Meanwhile, observation was also made for their effect on body and brain development in weaning mice.

Computer-molecular modeling analyses was used to identify the nootropic potency of piracetam and (±) 、 (-) clausenamide. The other methods and techniques used in present study include measurement of neurotransmitters, secondary messengers (〓, cAMP, cGMP, PKC, 〓) , membrane ion pump (〓ATPase, 〓ATPase) , ion channel, hippocampal slices potential, quantitative analysis of synapses and activity-dependent synaptic plasticity.

一. Comparison of effects of piracetam and (±) 、 (-) clausenamide on learning and memory given by single or multiple doses in mice.

Piracetam and (±) 、 (-) clausenamide were given once or multiple dosage by i. p. or i. g. to mice for observation of their effects on learning and memory in the step-down and step-through and water-maze tests as well as their effect on amnesia impaired by anisodine and 〓. The results showed that piracetam、 (-) clausenamide、 (±) clausenamide had no effect on acquisition of memory in step-down and step-through tests in normal mice, while they siginificantly reduced number of errors and time needed to reach the destination in amnesia model induced by anisodine and 〓 in water maze test. Their effective dose for piracetam, (±) and (-) clausenamide was 500mg/kg, 100mg/kg and 10mg/kg respectively. Among which (-) clausenamide showed the most potent effect.

二. Computer-molecular modeling analyses of piracetam and clausenamide structural characteristics

Six kinds of nootropics (piracetam and its analogues) structure properities were analysized. Results indicated that they all possessed O=C-C-N-C=O group, suggesting that it may be the pharmacolophore of nootropics.

(-) Clausenamide showed good superposition with piracetam, the root mean square (RMS) value for least-square superposition of piracetam and (-) clausenamide was 0.298, while the RMS for piracetam and (+) clausenamide was 0.780. Using computer hydrophobic analyses, it was shown that piracetam has much stronger hydrophilicity around its pharmacolophore, (-) clausenamide possesses not only hydrophilicity pharmacolophore, but alse stronger hydrophobicity around two phenyl rings which is helpful for clausenamide to penetrate CNS through blood-brain barrier and reach target.

三. Study on the nootropic mechanism of clausenamide

There is a close relationship between monoamines and learning and memory. NE and dopamine are believed to have a role in facilitation of memory. For this, an observation of clausenamide on monoamines and their metabolites as well as monoamine oxidase B activity was carried out.

Successive oral administration of clausenamide at dosage of 30, 150mg/kg d-1 for 4 day. Norepinephrine (NE) , dopamine (DA) , serotonin (5-HT) and their metabolities DOPAC, HAV, 5HIAA in mouse cerebral cortex were measured by HPLC -ECD. The result showed that clausenamide at dosage of 30mg/kg could increase the DA content significantly.

150mg/kg of clausenamide caused an increase in content of NE, DA, 5-HT, while their metabolities DOPAC and 5HIAA decreased. Clausenamide had no obvious effect on monoamine oxidase B activity using HPLC-UV detector, indicating that increment of monoamines may involves another mechanism of action. The increase of monoamine induced by clausenamide could be attributed to its increase of intracellular 〓.

This may be the biological bases for elucidating the facilitation of memory induced by clausenamide.

Long-term potentiation (LTP) is a form of synaptic plasticity which can be elicited by a short chain of electrical pulses of 100HZ stimulation for 1-2sec at moderate intensity. By using extracellular record, we have examined the effect of (-) clausenamide on potential spike (PS) and LTP in rat hippocampus slices. It was found that (-) clausenamide could increase PS and LTP amplitude markedly.

It is well known that calcium is an intracellular secondary messenger which plays a role in the development, proliferation, differentiation of cells and induction of learning, memory and LTP. The effect of (-) clausenamide on cytosolic 〓 level was measured in dissociated neonatal brain cells using Fur-2/AM- a fluoresent calcium indicator.

Results showed that 10, 100μmol/L of clausenamide induced a rapid increment of intracellular 〓 in dose -dependent manner. In addition, (-) clausenamide could increase cAMP content and elevated 〓ATPase activity, but had no any effect on cGMP content and 〓ATPase activity in rat brain synaptosome.

Using fluorometer method (-) clausenamide was shown to promote 〓-depentent and 〓-indepentent release of glutamate in guinea pig's cerebral cortical synaptosomes.

(-) Clausenamide could activate PKC activity of rat brain in prescence and abscence of DG in vitro, indicating that (-) clausenamide affect directly on PKC activity. Using 〓 -inositol, (-) clausenamide was shown to increase 〓 content in dose-dependent manner in rat hippocampal slices, As a result more calcium will be released from 〓 store.

In another study, the effects of clausenamide on the voltage-dependent potassium channels in isolated rat ventricular myocytes was observed with patch clamp whole cell recording technique. It was found that clausenmide reduced steady state-outward current and prolonged action potential duration in rat ventricular myocytes.

Administration of (-) clausenamide at dosage of 5, 10, 20mg/kg to weaning mice for 4 weeks. reduced gain of body weight was seen in the first week, but there was no difference in the gain of body weight between control and medicated groups in the next three weeks. It is interesting that chronic administration of (-) clausenamide induced facilitation of learning and memory in step down and step through tests. In the mean time, thickness of cerebral cortex and synapses density in the hippocampal 〓 region increased significantly.

In summary, clausenamide could improve memory impairment induced by anisodine and 〓. In water maze test and administration of clausenamide for 4 weeks, facilitation of memory or increase of learning ability in normal mice was also seen. Among (±) 、 (-) and (+) clausenamide, (-) clausenamide showed most potent effect.

Its nootropic effect was 50 times more potent than piracetam. This result was accordance with computer -molecular modeling analysis. The study on nootropic mechamism indicated that (-) clausenamide raised intracellular 〓 by increase of calcium influx and calcium release from calcium store. In the mean time, (-) Clausenamide increased 〓-dependent and 〓 -independent glutamate release. Both induced a series of physiological events such as increment of monoamines, PKC activity, synaptic effecacy and structureal plasticity, All of these events will finally lead to formation of LTP and facilitation of memory.

In summary, (-) clausenamide facilitated learning and memory; improved amnesia impaired by 〓 and anisodine; increased monoamines, promoted influx of calcium and 〓 release from calcium store; increased cAMP content and glutamate release in rat synaptosome; enhanced PS and Long term Potential (LTP) ; activated PKC and 〓ATPase activity; inhibited state-outward potassium current; prolonged action potential duration (APD) ; increased synapses density in hippocampus 〓 region, From these results, (-) Clausenamide is considered to be a promising nootropic agent.

i cant find anything about clausenamide anywhere. seems so obscure. i checked wiki but just the source is available http://en.wikipedia....lausena_lansium and it has zero mention of anything isolated from this plant. in fact, the article is pretty dull with just vague mention of the plant.

it relys on opioid activation similar to bacopa? Or perhaps just like bacopa, opioid activation is a secondary effect. http://www.ncbi.nlm....pubmed/10437155

i cant find anything about clausenamide anywhere. seems so obscure. i checked wiki but just the source is available http://en.wikipedia....lausena_lansium and it has zero mention of anything isolated from this plant. in fact, the article is pretty dull with just vague mention of the plant.

It was found and researched in China. So you can find more information using its chinese name "黄皮酰胺".

oh... It seems the forum dosen't support chinese characters....

lin, are you advertising products from a company you work for ?

There are no products yet.

There are still no products yet.

Anyway, Thanks a lot lin

http://www.ncbi.nlm....pubmed/19657451

wow...cortical thickness increase. anyone find a source on this? 

I'm interested in finding a legitimate source.

Bump

Ali baba offers only leaf extracts

(beside possible questionalbe quality)

http://www.alibaba.c...ium-wampee.html

Edited by Flex, 27 April 2015 - 11:20 AM.

chinese? go ahead, go wild.

What if someone messaged ceretropic perhaps they can source it for a fee?

chinese? go ahead, go wild.

 

lol I know, I know.

I´ve suggested this because theres litterary no other source, so didnt know where else to look.

Edited by Flex, 29 April 2015 - 01:33 PM.

wow...cortical thickness increase. anyone find a source on this?

If DocDimethyl's opinion is worth anything:

"I'd be dubious about the claims of increasing cortical density: 1) that may not be a good thing, 2)is there a control to show that it is not simply from learning."

http://www.reddit.co...4/clausenamide/

I haven't found a alternative source for Clausena lansium extract however there is a nursery 40 minutes away from me that sells Wampee trees.

https://plantogram.com/product/wampi/

Ok cool I located a source for Huang Pi He (Seed of Chinese wampee) and Huang Pi Ye (Leaf of Chinese wampee)


http://www.vitapharmusa.com

what does wampee fruit has to do with l-clausenamide??

what does wampee fruit has to do with l-clausenamide??

Nothing. Clausenamide is isolated from the leaves.

Sry, my mistake

Ok cool I located a source for Huang Pi He (Seed of Chinese wampee) and Huang Pi Ye (Leaf of Chinese wampee)


http://www.vitapharmusa.com

 

Did you experienced any effect?

I was gonna suggest alibaba but someone allready look into that and they only have the extract.

 

Wheter an extract works or not depends on the dose needed of the active compound and the ammount in the extract, any info on both?

OMG this looks "crazy cool" ;D

December 2014, Vol.4(6)

Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action

http://www.sciencedi...211383514001038
Edited by sativa, 28 February 2016 - 08:03 PM.

medievil how come i cant send you message?

Im banned from sending messages to ppl because of what happened in the past when i wanted to sell meds and ended up taking ppls money because i had to buy stims, which i deeply regret happened, either way you should be able to email me, theres a link on my profile i think another member did it, or post a way to contact you

Any sources for Clausena lansium leaves? Aside from picking them in person on location

Any sources for Clausena lansium leaves? Aside from picking them in person on location

 
Try to find Spiraea japonica, seems much more interesting.

 

wow this stuff is like the Gary Johnson (the political guy) of the nootropic world, why did no one vote for him? 

• improves learning of healthy mice
• promotes neurogenesis and LTP
• boost dopamine, probably via NET inhibition
• increases cAMP, PKC, ATPase
• reduces bodyweight
• anti-epileptic
• 50x potent as piracetam
• completely natural

 

what's so good about Spiraea japonica?  it's classified as an invasive weed, lol. 

 

Contrary to metagene's statement, I found some evidence that wampee fruit does have some interesting properties and clausenamide.  Wampee fruit is easier to find than the leaves, although it would be quite expensive and unpleasant to consume the required amount (~200g daily).

 

Previous studies on the bioactivities of wampee mainly
focused on its leaves, stems and seeds which showed hepatoprotective activity [4], hypoglycemic [5],
antifungal and antiviral activities [6], antiplatelet [7], anticancer [8], anti-inflammatory, antidiabetic and
antioxidant activities [9]. It is also applied as a folk medicine in India and China for the treatment of
stomachic and bronchitis, and it acts as a vermifuge as well. For the first time, this study examined the
neuroprotective effects of wampee peel extracts using H2O2 at high concentration as an inducer of
oxidative stress in vitro models [10], and further investigates its underlying mechanisms of action in
H2O2-induced PC12 cells. The current findings demonstrated that CLS partly reversed the apoptosis of
H2O2-induced PC12 cell via the NF-κB pathway and regulation of cellular redox status. We also
investigated the constituents from CLS. Seven major compounds, including a new flavanoid,
luteolin-4'-O-β-D-glucopyranoside (3) and six known compounds 1,2, 4–7 were isolated from CLS and
identified. The structures of these isolates 1–7 are shown in Figure 1A. Their antioxidative and
H2O2-induced PC12 cell apoptosis reversing activity were also evaluated.

The known phenolics were identified, by comparing of their spectroscopic data with data previously reported in the literature, as rutin (1) [11], quercetin-7-O-β-L-glucopranoside (2) [12], clausenamide (4) [13], quercetin (5) [12],(E)-3-(4-hydroxyphenyl)acrylic acid (6) [14] and benzoic acid (7).

Anyone tried or found a vendor of leaves, peel extract?