Artichokes boost memory through Long-Term Potentiaton

Artichoke Extract (Luteolin)

David Tomen
David Tomen
10 minute read
Artichoke Extract (Luteolin) has been shown to boost memory and learning, improve motivation and mood, and stimulate the growth of new neurons in the brain.

Artichoke Extract (Luteolin) is a natural PDE4 inhibitor in the brain. Excess PDE4 degrades cAMP. cAMP is important for neural signaling within brain cells.

As a secondary messenger in neurons, cAMP produces proteins needed for neuron and synapse growth. This process is called Long-Term Potentiation (LTP).

LTP is the process where synaptic connections get stronger in response to electrical stimulation in the brain. This process happens naturally through life experience. It’s a critical part of synaptic plasticity.

Brain structure changes over time through synaptic plasticity. And is how experience is recorded through learning and memory.

When PDE4 increases, cAMP is depressed. And learning, memory and mood suffer.

Artichoke Extract helps:

  • Neurotransmitters. Artichoke Extract inhibits PDE4 in the brain. Which stabilizes and increases cAMP. Boosting learning, motivation, memory and mood.
  • Neurogenesis. Artichoke Extract helps generate growth of dendrites on neurons. And helps reconstruct synapses, the junctions where nerve cells communicate with other neurons. Boosting memory and restoring neural networks.
  • Reduce Inflammation. Artichoke Extract helps reduce inflammation in the brain. By preventing the over-production of cytokines, and taming the flames of inflammation in neurons. Preventing memory loss and neurological dysfunction.


Artichoke Extract (Luteolin)

Artichoke Extract contains a naturally occurring compound called luteolin. Luteolin is a powerful phosphodiesterase (PDE4) inhibitor. Excess PDE4 in your brain is bad news because it degrades cAMP.

Cyclic adenosine monophosphate (cAMP) is a derivative of adenosine triphosphate (ATP). ATP is produced within mitochondria in each of your cells. cAMP is part of that cellular energy source.

As a secondary messenger in neurons, cAMP helps produce proteins for increased neuron growth. Neuron dendrites connect to other neurons through a process called Long-Term Potentiation (LTP).

LTP creates an increase in the production of cAMP. Which triggers a biochemical cascade of reactions. These effects reveal themselves to us as learning and memory.

When cAMP is degraded, it interferes with efficient brain signaling. And interferes with Long-Term Potentiation. Making it harder to develop memories, and to learn.

Artichoke Extract reduces PDE4. When PDE4 is reduced, you not only maintain healthy cAMP cellular energy. Brain signaling is actually amplified.[i]

When luteolin is combined with another natural herb called Forskolin, you get double duty. Luteolin reduces PDE4 which maintains cellular signal strength. And Forskolin boosts cAMP. Increasing brain signal strength.

Artichoke Extract (Luteolin) vs. Pure Luteolin: What’s the Difference?

Luteolin is not bioavailable on its own if taken as a supplement.[ii] It requires the presence of other naturally occurring bioflavonoids to be metabolized by your body. And to reach the cells in active form.

Artichoke Extract contains the compounds apigenin-7-rutinoside and narirutin, which unlocks Luteolin’s potential to work in your cells.[iii]

Artichokes boost memory through Long-Term Potentiaton

How does Artichoke Extract Work in the Brain?

Artichoke Extract boosts brain health and function in several ways. But two in particular stand out.

  1. Artichoke Extract inhibits PDE4 which boosts cAMP activity in brain cells. cAMP helps stimulate the production of CREB (cAMP response element-binding protein).

An increase in CREB enhances Long-Term Potentiation (LTP). LTP is the connection between brain synapses. Strengthening in response to stimulation by neurons on either side. A major component in both learning and memory.

Memories are stored at a cellular level. And retrieved at a cellular level. This well-travelled pathway is strengthened by boosting cAMP with Artichoke Extract.

This improvement in memory was demonstrated by researchers at the University of Genoa in Italy. Rats and mice were used in this study. The PDE4 inhibitor used was a chemical derivative of rolipram. (Rolipram cannot be used in human patients because it causes vomiting).

Results of the study showed this derivative enhanced memory function even at low doses. Acting on the same neural pathways as Artichoke Extract in humans.[iv]

  1. Artichoke Extract reduces brain inflammation.

Researchers studied the effect of Luteolin on immune system cells in the brain called microglia.

Microglia produce cytokines in response to infections and toxins. Over-production of cytokines results in inflammation and the destruction of neurons.

Aritchoke Extract reduced brain inflammationIn this study, brain cells in mice were pretreated with Luteolin before being exposed to a substance that induced inflammation in brain cells. The same type of inflammation humans experience from daily exposure to toxins.

The study showed that Luteolin offered protection against brain inflammation. And its consequences, including problems with cognition and memory.

The research team concluded that Luteolin “may be useful for mitigating neural inflammation”.[v]

How things go bad

Environmental factors, ADHD, illness, stress and aging changes our brain chemistry.

↓ Mood and motivation declines

↓ Memory and recall declines

↓ Long-term memory fades

All of these changes are contributing factors to poor quality of life. And as they progress, to neurodegenerative diseases like Alzheimer’s, dementia and Parkinson’s.

Artichoke Extract Benefits

Research from hundreds of studies, and feedback from neurohackers have shown that Artichoke Extract can:

  • Improve memory by inhibiting PDE4 in the brain (which boosts cAMP activity)
  • Boost dopamine levels in the brain
  • Tame inflammation in the brainArtichoke Extract to the rescue

Artichoke Extract is water-soluble and quickly enters your brain after you take it. Once in your brain, it inhibits PDE4 which boosts cAMP activity. cAMP is involved in the Long-Term Potentiation process of preserving memories.

Artichoke Extract combined with Forskolin is even more effective. Because not only are you helping cAMP activity in the brain, you’re boosting it with Forskolin.

Inhibiting PDE4 and boosting cAMP also makes the effect of normal dopamine production more effective. Boosting processes in this stream of chemical reactions in the brain increases learning and memory.[vi] Without the side effects of stimulating dopamine production through the use of drugs like Adderall or Ritalin.

How does Artichoke Extract feel?

Many neurohackers report that Artichoke Extract with Forskolin improves mood. It motivates you to want to learn, and to get things done. Some say it works as good as Modafinil.

Artichoke Extract boosts moodThe general consensus is:

  • Improved mood and motivation
  • Increased ability to study
  • Increased ability to retain information
  • Improved long-term memory

Artichoke Extract Clinical Research

Microglia cells are immune cells in your brain and spinal cord. They produce signaling molecules called cytokines. These cytokines are cell signaling molecules that aid communication between cells in immune responses.

When microglial cells are not regulated, they produce excessive levels of cytokines. And inflammatory cytokines kill neurons. Leading to cognitive aging and neurodegenerative diseases like Alzheimer’s. And are responsible for producing symptoms like sleepiness, loss of appetite, memory deficits and depression.

Researchers at the University of Illinois at Urbana–Champaign worked with a group of young, and older mice. The mice were fed a control diet, or a luteolin-supplemented diet for 4 weeks.

The research team found that luteolin helped regulate microglial cells. And stopped them from producing excess cytokines. This reduced inflammation in the brains of aged mice. And restored memory to levels observed in younger mice.[vii]

Artichoke Extract Improves Mood

Users report that Artichoke Extract boosts mood. Researchers at Kurume University School of Medicine in Japan demonstrated in the lab how this boost in mood occurs.

When dopamine D1 receptors in the prefrontal cortex of the brain malfunction, psychotic symptoms and other nasty symptoms show up. Including schizophrenia.

The study group found that dopamine D1 receptors signal through the cAMP cascade. Which is modulated by PDE4 enzymes.

In this study, researchers inhibited PDE4 production in the lab. Showing that an increase in dopamine resulted in influencing cognitive function. Proving the antipsychotic action of suppressing PDE4.[viii]

Artichoke Extract Improves Memory

Researchers at the West Virginia University Health Sciences Center in the USA worked with tame and wild-type mice. Suppressing PDE4 in the mice enhanced memory. And increased the growth of new neurons in the hippocampus of the brains in these mice.[ix]

Artichoke Extract Recommended Dosage

For PDE4 suppression: 900 mg Artichoke Extract per day

CILTEP Stack - Artichoke Extract + Forskolin + ALCAR + Caffeine
CILTEP Stack – Artichoke Extract + Forskolin + ALCAR + Caffeine

For boosting cAMP: 4 mg Forskolin (Coleus forskohlii) extract per day

Note: Check the label of the Forskolin supplement for the amount of actual Forskolin in each capsule. For example, 385 mg of Forskohlii may only be guaranteed to contain 3.85 – 4 mg of actual Forskolin. Which is what you need. Also note that more Forskolin is not better as it causes a strong fatigue effect at higher doses.

Forskolin 4 mg
Forskolin 4 mg

For counteracting Forskolin’s effect on Acetylcholinesterase: 800 mg Acetyl-L-Carnitine (ALCAR) – (200 mg of ALCAR for every 1 mg of Forskolin) per day

Many users of this stack report it helpful to supplement with 500 mg Phenylalanine, a B-Vitamin Complex and caffeine (coffee or preferably green tea).

Older biohackers may recognize the above recommended nootropic stack as the CILTEP stack.

Artichoke Extract Side Effects

Acetylcholinesterase is upregulated by cAMP which makes you sleepy. This means that available Acetylcholine in your brain drops. You can counteract this with Acetyl-l-Carnitine (ALCAR), which calms the upregulation of Acetylcholinesterase.

Artichoke extracts have been documented to lower blood cholesterol in human and animal studies. This means it may potentiate the effects of cholesterol-lowering and statin drugs.

Artichoke Extract affects the liver by stimulating the flow of bile. So if you have liver disease be careful about using this herb.

Artichoke Extract can also cause gallbladder contractions. So if you have gallbladder disease or gallstones, check with doctor before taking this herb.

Type of Artichoke Extract to buy

Two very different forms of artichoke are available. The Globe Artichoke (Cynara cardunculus) which has been cultivated and used since ancient times. And the Jerusalem Artichoke (Helianthus tuberosus) which is from the Northeastern USA.

All references to Artichoke Extract in this article is for the Globe Artichoke.

Users report that Artichoke Extract (Standardized to 5% Cynarins) of most premium brands are helpful in reducing PDE4.

Nootropics Expert Recommendation

Artichoke Extract (Luteolin) 900 mg per day

Nootropics Expert Tested and ApprovedI recommend using Artichoke Extract as a nootropic supplement.

Your body does not make Artichoke Extract (Luteolin) on its own. So you must take it as a standardized supplement.

Luteolin on its own as a supplement does not appear to be effective. Luteolin is not bioavailable so your body can’t use it. Luteolin as part of the Artichoke plant is used by your body. Because it contains other flavonoids that help your body absorb it.

Artichoke Extract is especially helpful when combined with Forskolin. It helps boost memory, increases motivation and the desire to learn. And helps improve mood.

We suggest dosing Artichoke Extract at 900 mg per day taken in the morning. With 4 mg of Forskolin. Stack this with 800 mg of ALCAR to keep your acetylcholine levels up.

We’ve also found that combining this Artichoke Extract stack with caffeine is helpful. The L-Theanine in green tea works with the caffeine boost we need. Without the side effects of coffee.

We’ve also found that more in not better with this stack. And taking it early in the day is good for a productive day. The effects last all day.

And finally, we are making the effects of normal dopamine function more effective with this stack. It triggers the desirable downstream processes that increase learning and memory.

The chemical dynamics of the dopamine system are preserved. And we don’t get the negative side effects of using a stimulant like Adderall or Ritalin.

This Artichoke Extract (Luteolin) stack increases mental endurance for encoding long-term memories.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] Barad M., Bourtchouladze R., Winder D.G., Golan H., Kandel E. “Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory” Proceedings of the National Academy of Sciences USA 1998 Dec 8; 95(25): 15020–15025. (source)

[ii] Shimoi K. et. Al “Intestinal absorption of luteolin and luteolin 7-O-β-glucoside in rats and humans” FEBS letters Volume 438, Issue 3, 6 November 1998, Pages 220–224 (source)

[iii] Wang M., Simon J.E., Aviles I.F., He K., Zheng Q.Y., Tadmor Y. “Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.).” Journal of Agricultural and Food Chemistry 2003 Jan 29;51(3):601-8. (source)

[iv] Brun o. et. Al. “GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses.” British Journal of Pharmacology 2011 Dec;164(8):2054-63. (source)

[v] Jang S., Kelley K.W., Johnson R.W. “Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1.” Proceeding of the National Academy of Sciences USA 2008 May 27;105(21):7534-9. (source)

[vi] Almeida L.E., Murray P.D., Zielke H.R., Roby C.D., Kingsbury T.J., Krueger B.K. “Autocrine activation of neuronal NMDA receptors by aspartate mediates dopamine- and cAMP-induced CREB-dependent gene transcription.” Journal of Neuroscience 2009 Oct 7;29(40):12702-10. (source)

[vii] Jang S., Dilger R.N., Johnson R.W. “Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice.”The Journal of Nutrition 2010 Oct;140(10):1892-8. (source)

[viii] Kuroiwa M. et. Al “Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA/DARPP-32 signaling cascade in frontal cortex.” Psychopharmacology 2012 Feb;219(4):1065-79. (source)

[ix] Li Y.F., Cheng Y.F., Huang Y., Conti M., Wilson S.P., O’Donnell J.M., Zhang H.T. “Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling.” Journal of Neuroscience2011 Jan 5;31(1):172-83. (source)

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Join The Discussion - 38 comments

Michael M.
April 5, 2024

David, I read your page ‘Artichoke Extract (Luteolin)’.

I’m taking 385 mg/day of Solaray Coleus Forskohlii (1% Forskolin) with Jarrow Artichoke Extract. I want to try a bioflavonoid formula with just luteolin and rutin, no apigenin, because of the following effects:

‘However, others have shown that apigenin (2) inhibited the production of 5α-androstane-3α, 17β-diol (DIOL), the main androgen of rat immature Leydig cells [29]. The activity of rat Hsd3b, Cyp17a1, and Hsd17b3 was inhibited by apigenin (2) with IC50 values in the 10 µM range [29]. In addition, human HSD3B2 and HSD17B3 were more than five times more sensitive to the inhibitory action of apigenin (2). Using H295R human adrenal cells, treatments with 10 µM apigenin for 24h resulted in a decrease of androstenedione and testosterone production [30,31]. In this cell model, apigenin (2) decreased the expressions of HSD3B2 and CYP17A1 [31]. Overall, apigenin (2) seems to increase steroidogenesis in Leydig cells mainly by increasing PKA-dependent StAR protein expression. However, such effect may not translate into increased testosterone production as we have also reported that apigenin (1) inhibits Cyp11a1 expression in LC540 tumor Leydig cells [25].’ – Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

How many milligrams of luteolin do you think are required to sufficiently inhibit PDE4 for the application you described on your page?

    David Tomen
    April 8, 2024

    Michael, you need 900 mg to suppress PDE4.

October 7, 2023

What herbs could be a substitute for artichoke, could mixed herbs like parsley basil sage ect the ones in the kitchen cupboard drank as a tea do more or less the same job?

    David Tomen
    October 10, 2023

    There is no direct “substitute” for Artichoke Extract. But Resveratrol and Oat Straw extract are also PDE4 inhibitors. Making a tea from the plant is not going to provide the same benefit as a concentrated extract of that plant.

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