Focusene

Focusene™

Natural Memory and Focus Supplement

A comprehensive natural nootropic supplement designed to improve focus and attentiveness using the latest advances in the fields of psychology, nutrition, herbal medicine and neuroscience.†

Ships in 24 hours

Made in America

Money-back guarantee 60 days

Focusene™

Natural Memory and Focus Supplement

A comprehensive natural nootropic supplement designed to improve focus and attentiveness using the latest advances in the fields of psychology, nutrition, herbal medicine and neuroscience.†

Monthly Auto-Ship Program

Get one Month’s Supply Shipped Automatically Each Month – With a Nice Discount. You Can Cancel Easily at Any Time

$39.95/ month No-Drama Cancellations

One-Time Order Options

1-Bottle $49.95 ($49.95 / 1 bottle)
3-Bottles $99.95 $149.85 ($33.32 / 1 bottle)
6-Bottles $179.95 $299.70 ($29.99 / 1 bottle)
$39.95/mo

Ships in 24 hours

Made in America

Money-back guarantee 60 days

BENEFITS

 Fight inattentiveness and distraction

Fight inattentiveness and distraction†

Support cAMP, a kind of cellular energy used by brain signals

Support cAMP, a kind of cellular energy used by brain signals†

Feed your brain’s focus and memory systems†

Feed your brain’s focus and memory systems†

Support mental performance: Focus, Memory and Sharpness

Support mental performance Focus, Memory and Sharpness†

No Soy, Gluten, GMOs

No: Soy, Gluten, GMOs

† Results may vary

WHAT CLIENTS SAY

  • “Keeps me sharp.”

    Since I was a child, focusing on the task at hand has always been a struggle. For years, doctors tried to have my parents, and me now as an adult, take [prescription medications]. No thank you! I tried some natural alternatives and still no luck. With hope, I tried out Focusene and I am so happy to have never lost hope! Focusene keeps me sharp and the time I take to finish many tasks has dropped nearly in half. Since taking it for a few months now, I feel like my mental clarity is stronger even when I haven’t taken it that day!†

    Matt B.

    Kansas City, KS

  • “Focusene is my go-to supplement for productivity and focus.”

    These days, it’s hard to find a supplement that works consistently over the course of months. I’ve tried many different supplements for productivity, ranging from “harder” nootropics like Modafinil and racetams, to milder blends.

    Focusene is the only blend that’s stood the test of time!†

    Danny Fries

    Founder, Corpina Nootropics blog, corpina.com

  • “I take it at the office.”

    I work in an open space office with about 50 people buzzing about, all in my line of vision. That alone is overwhelming. Add in three (ever changing) project deadlines, and I’ve got way too much to keep track of! One day I decided that I should look into herbal ways to focus in such stressful and often chaotic setting. I found it in Focusene!†

    Maddy J.

    Chicago, IL

  • “Great for studying and writing papers.”

    Focusene to the rescue! Within 20 minutes of taking it, my thoughts are clear and I start getting things done. No more having to read a paragraph two three times just to actually know what it says. No more taking hours to write a one page paper for class. Thank you!†

    Jessica L.

    Stamford, CT

  • “In the zone!”

    Bye bye scatterbrain, hello focus! I take it every day and it keeps me zoned in on what’s important.†

    Daniel B.

    Scranton, PA

  • “Natural [attention] Support? Wow!”

    My family and I are “all natural” junkies! So when my sister told me that she may have found a natural way to help me with me with what a doctor diagnosed me as, ADHD, I was beyond excited. Refusing to take prescription medications, my poor attention span has made life a little hard to say the least! After the first dose, after only about 15 minutes, I started to feel the benefits. PLUS, its so affordable!†

    Larry D

    Joshua, TX

  • “Works fast.”

    This stuff really works. And I have had no weird side effects. Would definitely recommend.†

    Andrew P.

    Hesperia, CA

  • “Protects my brain from forgetfulness.”

    The older I get the more trouble I have with focusing and remembering things, thus I wanted some help. I did some research, checked in with my natural pharmacist about all the ingredients and he said it was worth a try. So I tried it out, and guess what? It works! And the price?! A steal when you look at everything in the capsules.†

    Lori A.

    Evanston, IL

  • “Didn’t want to be on meds.”

    The last thing I wanted to do to finally have focus was take a medication that is basically speed! Thank goodness there is an effective, NATURAL way to help me stay focused. Plus after taking it for about three months now, I feel like even when I don’t take it, I can focus. Talk about a miracle. You gotta try it!†

    Mike B.

    Ithaca, NY

† Results may vary

OVERVIEW

Man in a leather jacket riding a motor bike

Keeps Your Brain on Track

Having focus and attentiveness problems is a lot like walking up a downward-moving escalator. You get where you’re going eventually, but is a frustrating and exhausting journey to get there. We’ve researched the perfect mix of natural compounds that studies showed improved patients’ focus, attention and memory. These compounds work together with one goal: keeping you sharp.

Effective Natural Focus

While our botanical blend works to quickly give you a boost focus and a natural bump of energy, our scientifically-formulated cognitive support system works with your body to build long-term brain balance and mental clarity.†

A woman holding a bow and arrow about to shoot
Healthy food products in bowls

All Natural

Focusene’s unique formula brings together the best of western science with the world’s most effective naturopathic herbal cognitive enhancers for a safe and effective natural focus and mental enhancement formula. And unlike many of the hard drugs pharmaceutical companies push, Focusene™ is all-natural and non habit-forming.†

Research Supported

Most of the ingredients in Focusene’s formula have been shown in studies to benefit people who suffer from attention and memory problems. Not convinced? Then we urge you to take a look at the documentation in our Clinical Research section.†

A doctor's hand writing a note on a notepad
Two chairs looking out over tropical paradise

Convenient

We at Tranquility Labs LLC are confident that you will find Focusene™ more effective than any other all-natural mental focus supplement on the market, guaranteed. If you are suffering from attention problems or could use some improvements to your memory, focus and mental sharpness, you can benefit from the Focusene™ Auto–Ship Program.†

INGREDIENTS

Focusene™ has been scientifically formulated to support and boost brain function using the latest advances in the fields of psychology, nutrition, herbal medicine and neuroscience. Focusene™ is the only all-natural supplement that offers a complete set of precursors (“building block ingredients”) for Dopamine and Acetylcholine – the two most important brain chemicals for focus, short term memory and brain signal processing. Here are the main components:

Dandelion

Dandelion

Dandelions are rich in Luteolin1, a powerful PDE4 inhibitor2. PDE4 inhibitors have been scientifically shown to improve memory3 4 5, wakefulness6 and general cognition5 7. This is chiefly because PDE4 – when left alone – has the effect of breaking down cAMP8, a form of chemical energy that helps your brain process thought signals8. Dandelion has roughly 10 times the Luteolin content of artichoke extract, one of the most popular natural nootropic luteolin sources9 10. We are the first company to feature dandelion as our preferred source of Luteolin.

Forskolin

Forskolin

Forskolin, the active compound in the Coleus Forskohlii plant11, has been shown to boost cAMP levels in the brain12. To put it simply, cAMP is a form of cellular energy responsible for processing brain (and other) signals13 14. Boosting cAMP is like turning up the dial on the strength of your brain signals14 15. Combined with luteolin, Forskolin has been scientifically shown to increase the strength and duration of cAMP in brain cells16.

Phenylalanine

Phenylalanine

An amino acid often found in nuts and legumes that is a known precursor to Dopamine17 and Acetylcholine, two of the most important neurotransmitters in the brain for regulating memory18, concentration, focus and brain signals19. Having more Phenylalanine available in your diet means having more of the essential building block of the concentration-center of your brain.

L-Theanine

L-Theanine

L–Theanine, an amino acid found in green tea20, increases the activity of GABA21, a neurotransmitter that helps reduce physical tension, among other functions22. L–theanine also stimulates the release of dopamine23, a neurotransmitter frequently out of balance in those who suffer from poor concentration or attention deficit24 25.

Acetyl-L-Carnitine

Acetyl-L-Carnitine

Shown to boost physical and mental energy naturally26, ALCAR is an antioxidant amino acid derived from the less bioavailable L-Carnitine27. L-Carnitine is produced in the liver28 and also ingested in some foods. ALCAR works as a procurer to the neurotransmitter acetylcholine29, which impacts attentiveness and memory19. Optimizing acetylcholine has been shown to positively impact mental focus19 as well as improve sleep and mood30 31. Within Focusene™, ALCAR works to counter the acetylcholinesterase – which can be bad for focus – created by increasing cAMP.

Grape Seed

Grape Seed

Grape seeds contain powerful antioxidants as well as a high concentration of vitamin E, flavonoids, linoleic acid and phenolic procyanidins (OPCs)32 33 34. There are a number of potential benefits to supplementing with Grape Seed Extract, but OPC’s are possibly the most important34. Lab studies have shown that OPCs help regulate the neurotransmitters dopamine and norepinephrine, which are implicated in attention deficit functioning and impact focus, concentration and memory35. Grape Seed Extract also helps better enable your blood to transport vital nutrients to the brain35.

Brahmi (Bacopa)

Brahmi (Bacopa)

Often used by Ayurvedic healers, Bacopa is traditionally prescribed to promote healthy cognitive function, including focus, concentration, mental endurance and memory36 37 38. Modern studies also support Bacopa as a strong anxiolytic (anti-anxiety) remedy39.

Deanol

Deanol

Deanol is needed to build the chemical choline40. Having more choline in the body has been shown to increase the production of acetylcholine, which is critical to brain and nervous system function41 42. There is a growing body of research in support of using DEANOL in fighting attention problems as well as cognitive decline43 44.

Vitamin B6

Vitamin B6

Getting enough of the many forms of Vitamin B is essential to maintaining proper brain function45. Vitamin B is involved in the metabolism, as well as the production of Serotonin46. Low levels of Vitamin B have been linked to anxiety, restlessness, fatigue, irritability, and emotional instability47.

Gingo Biloba

Gingo Biloba

The ginkgo tree is a living fossil that produces leaves that have been used medicinally since early human civilization48. Extracts made of these leaves have powerful impact on cognitive ability49. Ginkgo is commonly used as a nootropic to enhance memory50 and concentration49 and strengthens the function of the serotonin, dopamine, and norepinephrine neurotransmitters51. It has also been proven to fight cognitive decline52.

Red Ginseng

Red Ginseng

Asian ginseng has been used for many centuries for a variety of traditional uses, including the memory enhancement53 and the alleviation of anxiety and depression54. Often used in traditional Chinese medicine to promote vigor and healthy blood55, ginseng is one of the oldest herbal remedies in eastern medical traditions56.

HOW IT WORKS

Focusene gives the distracted brain targeted nutrition to support focus and memory neurotransmitters – and then turns up the dial of mental performance with a powerful herbal boost. In the end what you have is a two-part formula giving you a Nootropic Supercharge as well as long-term focus and memory support. First some background on what is often going on when you have focus, attention or memory problems. Arguably, the three most important neurotransmitters involved in focus, concentration, memory and general cognition are: dopamine, norepinephrine and acetylcholine. Let’s look at what each of these does in your brain.
Dopamine
  • Commonly out of balance in those suffering from attention deficit and other cognitive disorders57
  • Helps regulate motivation, cognition, learning and cognitive alertness58
  • Also plays a role in cellular and motor function59
  • Synthesized from Phenylalanine60
Norepinephrine
  • Neurotransmitter most responsible for vigilant concentration61
  • Involved in alertness, arousal and the brain’s reward system62
  • Commonly deficient in cognitive decline patients63
  • Synthesized from Dopamine64
Acetylcholine
  • Heavily involved in brain signal processing (neurotransmission)65
  • Increases responsiveness to sensory information66
  • Involved in learning and memory65
  • Is naturally inhibited by acetylcholinesterase67

Nootropic Brainpower Turbocharge

Wait, what the heck is a “nootropic?” We can’t hold it against you if you don’t know; it is a very new concept. Nootropics are both natural and chemical “smart drugs” that range from ginkgo biloba (the original nootropic) to the “racetam” family of experimental psychoactive chemicals. Every ingredient in Focusene is natural and regarded as safe by the FDA. This is not true of many other nootropics. For the first few weeks of taking Focusene, you should notice the effects of the fast–acting ingredients most strongly. First, Forskolin and Luteolin have been shown to boost the brain’s cAMP68 69 70, a form of cellular energy involved in brain signal processing. cAMP, in basic terms, helps the brain to interpret and react to signals once they are delivered. To round this out, a healthy dose of Ayurvedic bacopa provides an extra herbal kick. In basic terms, it is like turning up your brain’s “processor speed,”.

Long-Term Cognitive Support System

The key to why Focusene™ grows even more effective over time are the nutritional ingredients. We have all heard the phrase, “you are what you eat.” This is as much true for your mind as it is for your body. There are many nutrients in your brain that are critical to mental performance but are not very abundant in everyday food. The brain needs to constantly build natural chemicals like choline, acetylcholine, GABA, Dopamine, Norepinepherine and many more. To do this, it needs precursors or “building block” ingredients. Focusene™ is loaded with these precursors. Phenylalanine, for example, is a precursor for both acetylcholine and dopamine – both critical for mental responsiveness. To put it simply, the combination of Vitamin B6, L-Theanine, DMAE, and L-Phenylalanine work to build and balance out those critical neurotransmitters and supporting nutrients in the brain. However, this does not happen overnight. With chemical balance and high mental performance as the main goals, the formula works with your body over time, working toward balance and harmony in your mind’s support systems.
Results may vary.

IS IT RIGHT FOR ME?

Is Focusene™ for me?

  • Do you have regular difficulty staying focused on important tasks?
  • Are you easily distracted?
  • Do you have trouble organizing your life (bills, job, schedule, family matters)?
  • Do friends or loved ones sometimes accuse you of not listening or paying attention?
  • Are you often restless, or unable to relax?
  • Do you often have trouble getting started on a new task?
  • Do you have trouble prioritizing and finishing important tasks?
  • Do you have difficulty remembering something after you just learned it?
If you answered yes to any of these questions, you may suffer from attention deficit — or at least could surely benefit from improved memory, concentration and focus. Focusene™ is an all–natural supplement designed to provide a FAST boost to focus while boosting your brain’s processing power. The formula also works toward creating a long term balance to many of the common brain systems that lead to poor focus and memory when out of balance. Our clinically proven ingredients combine the best in western science with the most effective in eastern herbal medicine, bringing you the safest, most potent formula on the market. But don’t take our word for it. We urge you to examine the clinical research that went into our unique formula. And read up on exactly how Focusene™ works.
Results may vary.

SAFETY INFORMATION

Focusene™ is safe, natural and usually well tolerated by the body. Most people who take Focusene™ do not experience side effects. When side effects do occur, they tend to be mild and short-lasting. You can safely take Focusene™ with most nutritional supplements and most prescription medications. Do not take Focusene™ with prescription stimulants. Focusene™ contains phenylalanine. Do not take if you have phenylketonuria. Please consult a physician before taking Focusene™ if you are pregnant or nursing. Recommended dosage is two capsules taken with water, either both in the morning, or one in the morning and one in the afternoon – as you see fit. It is not recommended that you exceed three capsules at a time or four in one day. Exceeding the maximum dosage is not dangerous, though it may lead to obsessive thoughts or headache. When taken as directed, Focusene™ is safe and poses no known short-term or long-term health risks.

Warning

Do not take if you suffer from phenylketonuria.

Possible Side Effects

While most people taking Focusene™ experience NO side effects, possible side effects can include:

  • Headache
  • Upset stomach
  • Excitation
Feel free to contact Focusene™ Customer Support if you have any questions or concerns.

FREQUENTLY ASKED QUESTIONS

Where is Focusene™ manufactured?

Focusene™ is made in the USA in a facility that meets FDA’s guidelines and was awarded the NSF seal for Good Manufacturing Practices (GMP). Sadly, many supplements available online are made in China. China currently has a bad track record with product contamination after lead was found in numerous products. We are proud to manufacture Focusene™ in the US.

What is the minimum age for taking Focusene

Focusene is recommended for adults age 18 and older. This is not because we have found Focusene to be unsafe for children, but because we believe parents should do their diligence to review the ingredients in anything they give their kids to ensure maximum safety.

How do I cancel my auto ship?

You can cancel at any time by emailing support@tranquilitylabs.com. Your cancellation will be processed within 48 hours.

How long will it take to reach me?

All orders are shipped USPS First Class with tracking. Orders are shipped within one business day and, for orders within the US, it should reach you within a week.

How long does Focusene™ take to work?

Our formula works in two parts: 1) to provide you with a quick boost of clarity and focus and 2) to help balance out nutrition in the areas of the brain responsible for your ability to focus and think clearly. The immediate effects can often be felt very quickly. The long term balance takes consistency, however, which is why we recommend taking Focusene™ for at least three or four months.

Do you offer free samples?

We are confident Focusene™ will work for you and want you to try the first bottle for a full month, risk free with our 60-day, money-back guarantee.

Is it shipped discreetly?

Yes, it comes in a plain brown package that simply bears our name “Tranquility Labs® LLC”.

How can I check the status of my order?

You can feel free to ask us about the status of your order at support@tranquilene.com, or use the tracking number supplied in your e-mailed receipt to keep track of your shipment’s location.

Can I take Focusene™ with my medication?

Focusene™ is a natural formula and safe to take with most medications. However, we do urge you to check with a doctor or pharmacist for any possible interactions if you are currently on any medications. For more information, visit our Safety Information page.

What is the recommended dosage of Focusene™ ?

Recommended dosage is two capsules taken with water, either both in the morning, or one in the morning and one in the afternoon – as you see fit. For maximum effectiveness, we recommend taking it 20 to 30 minutes before food. It is not recommended that you exceed three capsules at a time or four in one day. Exceeding the maximum dosage is not dangerous, though very high dosages of certain ingredients have not been studied long term.

How do I order Focusene™ ?

You can order online at Focusene.com, or call us at 888-407-9659. All you need is an address and your credit card.

What forms of payment do you accept?

We accept Visa, Master Card, American Express and Discover. We apologize, but we do not accept cash, checks, money orders or PayPal.

How can I be sure my information is secure?

Tranquility Labs® LLC only uses encrypted, PCI-compliant methods for storing and transferring customer data. Customer security is a top priority.

What is your guarantee?

Focusene™ orders come with a 60 day guarantee. If you are unsatisfied for any reason you may return the product within 60 days for a full refund of the purchase price.

Order Below

Focusene™

Natural Memory and Focus Supplement

A comprehensive natural nootropic supplement designed to improve focus and attentiveness using the latest advances in the fields of psychology, nutrition, herbal medicine and neuroscience.†

Ships in 24 hours

Made in America

Money-back guarantee 60 days

Focusene™

Natural Memory and Focus Supplement

A comprehensive natural nootropic supplement designed to improve focus and attentiveness using the latest advances in the fields of psychology, nutrition, herbal medicine and neuroscience.†

Monthly Auto-Ship Program

Get one Month’s Supply Shipped Automatically Each Month – With a Nice Discount. You Can Cancel Easily at Any Time

$39.95/ month No-Drama Cancellations

One-Time Order Options

1-Bottle $49.95 ($49.95 / 1 bottle)
3-Bottles $99.95 $149.85 ($33.32 / 1 bottle)
6-Bottles $179.95 $299.70 ($29.99 / 1 bottle)
$39.95/mo

Ships in 24 hours

Made in America

Money-back guarantee 60 days

  1. Chun Hu et al., (2004) studied Luteolin and luteolin-7-O-glucoside extracts from dandelion flower and their action in suppression of iNOS and COX-2 in RAW264.7 cells. Flavones, luteolin and luteolin-7-O-glucoside along with a rich plant source of both flavones, namely dandelion (Taraxacum officinale) flower extract were studied for antioxidant activity in different in vitromodel systems. In this current study, luteolin and luteolin-7-O-glucoside at concentrations lower than 20 µM, significantly (p < 0.05) suppressed the productions of nitric oxide and prostaglandin E2 (PGE2) in bacterial lipopolysaccharide activated-mouse macrophage RAW264.7 cells without introducing cytotoxicity. The inhibitory effects were further attributed to the suppression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression, and not reduced enzymatic activity. Similar suppression for both inducible enzymes was also found with the presence of dandelion flower extract, specifically, the ethyl acetate fraction of dandelion flower extract which contained 10% luteolin and luteolin-7-O-glucoside. http://link.springer.com/article/10.1023/B:MCBI.0000044364.73144.fe
  2. JIANG Dai-xun et al., (2015) studied the prevention fMLP-induced neutrophils adhesion by luteolin via suppression of LFA-1 and phosphodiesterase 4 activity. Luteolin is an active ingredient found early from Folium perillae and Flos lonicerae, and has a specific inhibition on phosphodiesterase 4 (PDE4) activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP (cAMP), is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 (MAC-1) in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. http://www.sciencedirect.com/science/article/pii/S2095311914609047
  3. K. Rutten et al., (2007) investigated the effect of rolipram, PDE4 inhibitor, in reversing the object memory impairment induced by acute tryptophan depletion in the rat. In addition, the levels of plasma tryptophan (TRP) were compared to object recognition performance. Rolipram (0.1 mg/kg) reversed the memory deficit induced by ATD in a dose-dependent manner. http://link.springer.com/article/10.1007/s00213-006-0697-4
  4. Fan-Shiu Tsai et al., (2007) investigated the ameliorating effects of luteolin on memory acquisition in rats. The effects of luteolin on scopolamine-induced impairment of passive avoidance response were evaluated primarily, as well as the role of the central nervous system through the use of central neurotoxins and central nervous antagonists. From the results, authors suggested that the attenuating effect of luteolin (10 mg/kg, i.p.) on the deficits of passive avoidance performance induced by SCOP may be related to the increases in the activities of central muscarinic and nicotinic receptors. http://www.sciencedirect.com/science/article/pii/S0024320507001373
  5. Bei Xu, Xiao-Xiu L et al., (2010) studied luteolin effect on long term potentiation of cognitive functions in chronic cerebral hypoperfused rats. The results of this study showed chronic cerebral hypoperfusion produced by 2-vessel occlusion significantly impaired spatial learning and memory, and luteolin reversed the learning and memory deficit. 2-vessel occlusion resulted in dramatic inhibition of LTP formation in the hippocampus and luteolin significantly rescued the LTP impairment. Flavonoid luteolin shows great potential as a novel treatment agent for protecting synaptic function and enhancing memory in neurodegenerative disorders. http://www.sciencedirect.com/science/article/pii/S0014299909009455
  6. Z. Lelkes et al., (1998) studied the effect of Rolipram, PDE4 inhibitor, that Increases the Availability of cAMP, Transiently Enhances Wakefulness in Rats. This study was carried out on the effects on sleep of rolipram, an antidepressant that increases the availability of cAMP by inhibiting a phosphodiesterase isoenzyme. The high (1 mg/kg) dose of rolipram enhanced wakefulness (W) in postinjection h 1 on day 1 of rolipram treatment. After administration of 0.1 mg/kg rolipram, only a tendency to an increase in W was noted. http://www.sciencedirect.com/science/article/pii/S0091305798000380
  7. Dae Young Yoo et al., (2013) studied the effects of luteolin on spatial memory in a scopolamine-induced amnesia model. Luteolin, a common flavonoid from many plants, has various pharmacological activities, including a memory-improving effect. The administration of luteolin or GAL significantly improved the spatial alteration percentage compared to that in the SCO-treated group. These results suggest that the luteolin treatment improves the SCO-induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus. The mechanism underlying the amelioration of SCO-induced amnesia by luteolin may be associated with the increase in BDNF, acetylcholine, and the decrease in lipid peroxidation. http://www.maneyonline.com/doi/pdfplus/10.1179/1743132813Y.0000000217
  8. James M et al., (2004) reviewed antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4). In general, clinically used antidepressants enhance noradrenaline-mediated and serotonin (5-HT)-mediated neurotransmission, either by inhibiting reuptake catabolism or by blocking inhibitory, presynaptic a-adrenoceptors (either autoreceptors or heteroreceptors). Thus, it was of interest to determine whether PDE4 is involved in signaling mechanisms that are associated with these two neurotransmitters . PDE4 was found to be either the predominant or exclusive PDE that mediates the hydrolysis of cAMP formed by stimulation of b-adrenoceptors in rat cerebral cortex. The available data indicate that PDE4 is a regulated component of cAMP signaling mediated by beta-adrenoceptors. Inhibition of PDE4 might produce antidepressant effects in part by altering noradrenaline-mediated neurotransmission. http://www.sciencedirect.com/science/article/pii/S0165614704000203
  9. Sullim Lee et al., (2011) have determined the luteolin and luteoloside content in dandelions using HPLC. The ultraviolet spectra were recorded at 350 nm for the identification of the two flavonoids. The contents of luteolin and luteoloside were highest in T. officinale flowers (5.817 ± 0.030 mg*g-1) and in T. coreanum leaves (6.205 ± 0.087 mg*g-1), respectively. The total content of luteolin and luteoloside in T. coreanum was about 1.3-2 times higher than that found in T. ohwianum and T. officinale. http://link.springer.com/article/10.1007%2Fs13580-011-0214-5
  10. Donatella Negro et al., (2012) have extracted polyphenol compounds in Artichoke Plant Tissues and Varieties. Polyphenol compounds, particularly caffeoylquinic acids and flavonoids, were measured in different tissues and developmental stages of 6 artichoke varietal types diffused in the Mediterranean region. Flower heads were subdivided into external, intermediate, internal bracts, and receptacle, while leaves were collected at the vegetative and productive stages. The main polyphenols detected were chlorogenic acid, cynarin, luteolin 7-O-rutinoside, and luteolin 7-O-glucoside. “Violet de Provence” artichoke proved to retain the highest content of total phenols. Single polyphenols accumulated preferentially in specific parts of capitula. In leaves, most polyphenols were detected in the productive stage of the plant. Altogether, results provide useful indications for the promotion of artichoke as nutraceutical food and for the extraction of health-promoting substances in particular tissues/stages of the artichoke plant. http://onlinelibrary.wiley.com/doi/10.1111/j.1750-3841.2011.02531.x/abstract
  11. Schaneberg, Brian T et al., (2003) developed a method of quantitative analysis of Forskolin in Coleus forskohlii (Lamiaceae) by Reversed-Phase Liquid Chromatography. A rapid method was developed for the evaluation of forskolin in Coleus forskohlii Briq. (Lamiaceae). The method was successful in the qualitative and quantitative evaluation of the marker compound in C. forskohlii plant material and in market products claiming to contain C. forskohlii. http://www.ingentaconnect.com/content/aoac/jaoac/2003/00000086/00000003/art00005
  12. F. Bernardo Pliego Rivero et al., (1999) have investigated forskolin-induced expression of tyrosine hydroxylase in human foetal brain cortex. Brain-derived neurotrophic factor (BDNF) has previously been shown by this and other laboratories to work in concert with dopamine (DA) to induce the dopaminergic phenotype in foetal rat and human cerebral cortex during specified sensitive developmental stages. In the present study this induction by BDNF/DA was found to be greatly amplified by adding forskolin (fsk: 10 μM) to the rat and human cerebral cortex cultures together with DA (10 μM) and BDNF (50 ng/ml). Since fsk boosts intracellular levels of cyclic AMP (cAMP), its amplifying action when added together with BDNF/DA is likely to be due to interactions via the cAMP response element/cAMP response element binding protein (CRE/CREB) systems. http://www.sciencedirect.com/science/article/pii/S0165380699000346
  13. Mayra Paolillo et al., (1998) have studied the type and the localization of cAMP-dependent protein kinase regulate transmission of cAMP signals to the nucleus in cortical and cerebellar granule cells. cAMP signals are received and transmitted by multiple isoforms of cAMP-dependent protein kinases, typically determined by their specific regulatory subunits. In the brain the major regulatory isoform RIIb and the RII-anchor protein, AKAP150 (rat) or 75 (bovine), are differentially expressed. Expression in cerebellar granule cells of RIIb and AKAP75 genes by microinjection of specific expression vectors, markedly stimulated cAMP-induced transcription of the lacZ gene driven by a cAMP-responsive element promoter. These data indicate that the composition of PKA in cortical and granule cells underlies the differential ability of these cells to transmit cAMP signals to the nucleus. http://www.jbc.org/content/274/10/6546.full.pdf+html
  14. Carolina Isiegas et al., (2008) developed A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval. Consistent evidence from pharmacological and genetic studies shows that cAMP is a critical modulator of synaptic plasticity and memory formation. This developed novel conditional genetic system in mice based on the heterologous expression of an Aplysia octopamine receptor, a G-protein-coupled receptor whose activation by its natural ligand octopamine leads to rapid and transient increases in cAMP. Findings of the study clearly demonstrate that acute increases in cAMP levels selectively in neurons facilitate synaptic plasticity and memory, and illustrate the potential of this heterologous system to study cAMP-mediated processes in mammalian systems. http://www.jneurosci.org/content/28/24/6220.short
  15. Susumu Ando et al., (1987) studied delayed memory dysfunction by transient hypoxia, and its prevention with forskolin. Rats were exposed to 40 min hypoxia 3 h before a one-trial learning passive avoidance task showed impaired memory retention 24 h later. This model was used to assess the ability of forskolin to restore the delayed memory dysfunction. Significant amelioration of memory retention was observed when forskolin (500 μg/kg, i.p.) was injected just after hypoxia. Forskolin is suggested to enhance cerebral blood flow and to facilitate memory function through the action of increased cyclic adenosine monophosphate (cAMP). http://www.sciencedirect.com/science/article/pii/0006899387903088
  16. Lian-Fang Lin et al., (2012) report for the first time that luteolin induces the persistent expression of microRNA-132 (miR-132) in PC12 cells. The correlation between miR-132 knockdown and a decrease in luteolin-mediated neurite outgrowth may indicate a mechanistic link by which miR-132 functions as a mediator for neuritogenesis. To evaluate the effects of luteolin on the expression of miR-132, PC12 cells were cultured in low-serum medium (1% horse serum and 0.5% FBS) and treated with vehicle (0.1% DMSO), forskolin (10 µM; as a positive control) or luteolin (20 µM) for the indicated period. The effect of the luteolin on cell viability in PC12 cell system was measured by MTT assay. Treatment of cells with forskolin and luteolin for 2 h significantly increased both the immature and mature forms of miR-132 and the induction remained for 8 h. This result indicates that luteolin up-regulates miRNA-132 in PC12 cells. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043304
  17. HC Lou (2008) studied dopamine precursors and brain function in phenylalanine hydroxylase deficiency. Phenylalanine and tyrosine constitute the two initial steps in the biosynthesis of dopamine, which, in its turn, is the metabolic precursor of noradrenaline and adrenaline. The extracellular phenylalanine concentration influences brain function in phenylalanine deficiency (PHD) by decreased dopamine synthesis. It has been shown to induce EEG slowing, and prolonged the performance time on neuropsychological tests. The tyrosine concentration in the CNS is reduced in PHD, possibly implying insufficient substrate (= tyrosine) for catecholamine synthesis due to competition inhibition, for instance across the blood brain barrier. http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.1994.tb13461.x/abstract
  18. Graham V. Williams et al., (1995) studied the modulation of memory fields by dopamine Dl receptors in prefrontal cortex. Dopamine has been implicated in the cognitive process of working memory but the cellular basis of its action has yet to be revealed. By combining iontophoretic analysis of dopamine receptors with single-cell recording during behaviour, it was found that D1 antagonists can selectively potentiate the ‘memory fields’ of prefrontal neurons which subserve working memory. The precision shown for D1 receptor modulation of mnemonic processing indicates a direct gating of selective excitatory synaptic inputs to prefrontal neurons during cognition. http://www.nature.com/nature/journal/v376/n6541/pdf/376572a0.pdf
  19. Michael E. Hasselmo (2009) reviewed the Role of Acetylcholine in Learning and Memory. Pharmacological data clearly indicate that both muscarinic and nicotinic acetylcholine receptors play a role in encoding of new memories. Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within this regions. There is increasing convergence of research on the role of acetylcholine in learning and memory. Top-down behavioral approaches have become more focused in using anatomically localized manipulations of cholinergic modulation. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659740/
  20. Lekh Raj Juneja et al., (1999) studied L-theanine a unique amino acid of green tea and its relaxation effect in humans. Since ancient times, it has been said that drinking green tea brings relaxation. The substance that is responsible for a sense of relaxation, is theanine. Theanine is a unique amino acid found almost solely in tea plants and the main component responsible for the exotic taste of `green’ tea. It was found that L-theanine administered intraperitoneally to rats reached the brain within 30 min without any metabolic change. http://www.sciencedirect.com/science/article/pii/S0924224499000448
  21. Pradeep J. Nathan et al., (2006) have studied the neuropharmacology of L-Theanine and its Cognitive Enhancing activities. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent. http://www.tandfonline.com/doi/abs/10.1080/J157v06n02_02#.VoaAoRV97IU
  22. A. N. Elias et al., (2000) studied the effect of GABAnergic tone physiological changes. Transcendental meditation (TM) is a stylized form of physical and mental relaxation which is associated with changes in the secretion and release of several pituitary hormones. The hormonal changes induced by TM mimic the effects of the inhibitory neurotransmitter gamma aminobutyric acid (GABA). It is hypothesized that TM produces changes in pituitary hormone secretion by enhancing hypothalamic GABAergic tone as a result of TM associated ketosis. Ketosis enhances the entry of glutamate, the amino acid substrate of GABA into synaptosomes, making more glutamate available for conversion to GABA through the glutamate decarboxylase pathway. http://www.sciencedirect.com/science/article/pii/S0306987799909210
  23. Hidehiko Yokogoshi et al., (1998) investigated the effect of Theanine on Brain Monoamines and Striatal Dopamine Release in Conscious Rats. The results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA. http://link.springer.com/article/10.1023/A:1022490806093
  24. Nora D. Volkow et al., (2007) studied the brain dopamine transporter levels in adults with attention deficit. Attention deficit hyperactivity disorder is the most frequent psychiatric disorder in children, yet data are sparse on its pathophysiology. Particularly relevant are the dopamine transporters since these are the main targets of stimulant medications used for its treatment. The results provides evidence that dopamine transporter levels modulate attention but suggest that additional pathology (e.g., prefrontal or cingulostriatal pathways, noradrenergic neurotransmission) is necessary to account for the large differences in inattention observed between controls and attention deficit subjects. http://www.sciencedirect.com/science/article/pii/S105381190601024X
  25. Gail Tripp et al., (2008) reviewed the hypothesis that changes in dopamine signalling might account for altered sensitivity to positive reinforcement in children with attention deficit. It is proposed that in children with attention deficit there is diminished anticipatory dopamine cell firing, which we call the dopamine transfer deficit (DTD). The DTD theory leads to specific and testable predictions for human and animal research. The extent to which DTD explains symptoms of attention deficit and effects of pharmacological interventions is discussed. http://onlinelibrary.wiley.com/doi/10.1111/j.1469-7610.2007.01851.x/full
  26. Mariano Malaguarnera et al., (2007) evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians in a clinical trial. The results of the study indicated that oral administration of levocarnitine produces a reduction of total fat mass, increases total muscular mass, and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions. http://ajcn.nutrition.org/content/86/6/1738.short
  27. Ilhami Gu¨lc¸in et al., (2005) have investigated the antioxidant properties of the l-carnitine were evaluated by using different antioxidant assays such as 1, 1-diphenyl-2-picryl-hydrazyl free radical (DPPHI) scavenging, total antioxidant activity, reducing power, superoxide anion radical scavenging, hydrogen peroxide scavenging and metal chelating activities. l-carnitine plays an important regulatory role in the mitochondrial transport of long-chain free fatty acids. Results of the study was found to be an effective antioxidant in different in vitro assay including reducing power, DPPH radical and superoxide anion radical scavenging, hydrogen peroxide scavenging and metal chelating activities when it is compared to standard antioxidant compounds such as a-tocopherol, a natural antioxidant, and trolox which is a water-soluble analogue of tocopherol. http://www.sciencedirect.com/science/article/pii/S0024320505009483
  28. John D. Palomb et al., (1986) presented a case report about improvement of liver function tests in carnitine deficient patients. Carnitine deficiency is a rare but often treatable cause of abnormal fatty acid metabolism. Carnitine, a quaternary amine involved in the transport of long chain fatty acids into mitochondria for oxidation and production of adenosine triphosphate (ATP), is normally synthesized in human liver and kidney from the amino acids lysine and methionine. http://pen.sagepub.com/content/11/1/88.extract#
  29. Helen L. White et al., (1990) demonstrated experimentally acetyl-l-carnitine as a precursor of acetylcholine. Results of the present study show that the transfer of the acetyl moiety of ALCar to ACh is dependent on ALCar concentration and represents a greater percentage of total ACh synthesis when acetylCoA concentration is low. Also, it is strictly dependent on the presence of CoA, the second substrate of the forward reaction of CarAT. When acetyl-CoA was not added to the incubation mixtures in experiments with isolated enzymes, no ACh was formed unless CoA was added to the system. http://link.springer.com/article/10.1007/BF00973749
  30. Marina R. Picciotto et al., (2007) studied the activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Nicotine can both activate and desensitize/inactivate nicotinic acetylcholine receptors (nAChRs). An ongoing controversy in the field is to what extent the behavioral effects of nicotine result from activation of nAChRs, and to what extent receptor desensitization is involved in these behavioral processes. Study concluded that there are effects of nAChR activation and desensitization on drug reinforcement and affective behavior, and that both processes are important in the behavioral consequences of nicotine in tobacco smoking. http://www.sciencedirect.com/science/article/pii/S0301008207002304
  31. Priyattam J et al., (1987) reviewed the acetylcholine and the regulation of REM sleep. In this review authorswe focused on and summarizing the evidence for the role of cholinergic mechanisms in REM sleep. New anatomical techniques have been useful in elucidating the role of the cholinergic system in REM sleep generation. Authors reviewed the evidence that a diffuse network of cholinoceptive neurons in the medial pontine reticular formation (PRF) primes, initiates, and maintains the consolidated state of REM sleep. http://www.annualreviews.org/doi/abs/10.1146/annurev.pa.27.040187.001033?journalCode=pharmtox
  32. According to the web page of University of Maryland Medical Center, Grape seed extracts is highly concentrated with vitamin E, flavonoids, linoleic acid, and OPCs. Lower concentrations of these compounds are also available in the skin of the grape, as well as grape juice and wine. Resveratrol is another compoud in grapes and grape skins that is related to OPCs. Resveratrol has become very popular as an antioxidant and is being studied in connection with a variety of diseases. https://umm.edu/health/medical/altmed/herb/grape-seed
  33. G K Jayaprakasha et al., (2001) studied the antioxidant activity of grape seed (Vitis vinifera) extracts in vitro. Antioxidant-rich fractions were extracted from grape seeds using various solvents, such as acetone, ethyl acetate, methanol and mixtures of different solvents, such as ethyl acetate (EtOAc) and water in 9:1, 17:3 and 4:1 ratios. Grape seed extracts may be exploitable for the preservation of food products as well as for health supplements and nutraceuticals. http://www.sciencedirect.com/science/article/pii/S0308814600002983
  34. Makoto Saito et al., (1998) investigated the antiulcer Activity of Grape Seed Extract and Procyanidins in rats. In this study, GSEs exhibit a protective effect on acute gastric lesions in rats. This activity may be due to longer procyanidins. http://pubs.acs.org/doi/abs/10.1021/jf9709156
  35. Dr.Marion Sigurdson, a psychologist in Tulsa, Oklahoma, reports that OPCs extracted from a mix of grape seeds and pine bark are as effective as methylphenidate(Ritalin) in the treatment of both adult and childhood attention deficit disorder (ADD).The manner in which OPCs affect ADD is not precisely understood, but laboratory studies suggest that OPCs help the brain to regulate its use of two excitatory neurotransmitters, dopamine and norepinephrine. This allows OPCs to act as antidepressant for people with ADD and also those with chronic fatigue syndrome without affecting nerve function in the rest of the body. According to recent research,OPCs also help deliver to the brain nutrients that are helpful for people with ADD,such as zinc,manganese,selenium,and copper.OPCs also relieve neurological symptoms by acting as antihistamines. http://www.mdidea.com/products/phytochemical/oligomericproanthocyanidins05.html
  36. Jobin Mathew et al., (2009) have reviewed Bacopa monnieri and Bacoside-A for ameliorating epilepsy associated behavioral deficits. Bacopa monnieri is an outstanding nervine tonic used for raising the mental performance. It helps in concentration, comprehension, recall and alertness, Brahmi is particularly beneficial as it aids in categorizing information in brain and its subsequent expression. Bacopa is also called as a natural antioxidant which may give details its neuroprotective role seen in the memory centers of the brain. http://www.sciencedirect.com/science/article/pii/S0367326X09002731
  37. Matthew P. Pase et al., (2012) reviewed the Cognitive-Enhancing Effects of Bacopa monnieri. Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans. http://online.liebertpub.com/doi/abs/10.1089/acm.2011.0367
  38. Chuenjid Kongkeaw et al., (2014) performed meta analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed ‘head-to-head’ trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation. http://www.sciencedirect.com/science/article/pii/S0378874113008027
  39. Carlo Calabrese et al., (2008) evaluated the effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and its safety and tolerability in healthy elderly study participants. Standardized extracts of B. monnieri have potential for safely enhancing cognitive performance in aging, an indication that is closely comparable to the traditional uses of the herb. http://online.liebertpub.com/doi/abs/10.1089/acm.2008.0018
  40. D. R. Haubrich et al., (1981) have investigated the effect of deanol on choline metabolism. Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors. http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.1981.tb00480.x/abstract;jsessionid=C59C1F8814E7DFA435AE6C50E28BF4FC.f02t03
  41. Dean R . Haubrich et al., (1975) studied the increase in rat brain acetylcholine induced by choline or deanol. Administration of choline chloride, deanol to rats subsequently killed by microwave irradiation caused an increase in the concentration of both choline and acetylcholine in the corpus striatum, indicating that synthesis of brain acetylcholine can be stimulated in vivo by elevating the tissue concentration of its precursor. This finding suggests that the concentration of free choline in brain is below that necessary for a maximal rate of synthesis of acetylcholine, and raises the possibility that the availability of choline in brain may regulate the rate of synthesis of acetylcholine. These results also provide biochemical evidence for the view that the clinical effects of deanol result from its conversion to acetylcholine. http://www.sciencedirect.com/science/article/pii/0024320575904518
  42. Edith L. Cohen et al., (1975) studied the Brain acetylcholine, Increase after systematic choline administration. Administration of choline chloride i.p. to rats causes a dose-dependent increase in the brain concentration of the neurotransmitter, acetylcholine (ACh). This increase is maximal (22% after a 60-mg/kg dose) 40 minutes after injection. These observations suggest that precursor availability may influence brain ACh synthesis, just as brain tryptophan and tyrosine levels have previously been shown to control the synthesis of brain serotonin and catecholamines. http://www.sciencedirect.com/science/article/pii/0024320575901940
  43. Jack W. Fleming et al., (2013) studied the effect of Deanol on Attention in the Mentally Retarded patients.Deanol is reported to be effective in reducing the incidence of some of the behaviours associated with emotional disturbance. Of the many behaviours said to show improvement, the ability to pay attention was studied in this study. http://onlinelibrary.wiley.com/doi/10.1177/009127006200200407/abstract
  44. Steven H. Ferris et al., (2015) investigated senile dementia treatment with deanol. Recent research indicates a possible cholinergic involvement in memory processes and thus the possibility that acetylcholine deficiency may underlie memory impairment in senile dementia. Deanol (2-dimethylaminoethanol), which is assumed to increase brain acetylcholine, was given openly for 4 weeks to 14 senile outpatients, to determine the safety of the drug and whether or not it reduces cognitive impairment. The results thus suggest that although deanol may not improve memory, it may produce positive behavioral changes in some senile patients. http://onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.1977.tb00407.x/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage
  45. Jacob Selhub et al., (2000) have reviewed the evidence of the importance of the B vitamins folic acid, vitamin B-12, and vitamin B-6 for the well-being and normal function of the brain derives from data showing neurologic and psychologic dysfunction in vitamin deficiency states and in cases of congenital defects of one-carbon metabolism. The status of these vitamins is frequently inadequate in the elderly and recent studies have shown associations between loss of cognitive function or cognitive decline and inadequate B vitamin status. Advances in the understanding of this putative relation between inadequate vitamin status and loss of cognitive function in the elderly are likely to be slow and may depend on the outcomes of both prospective studies and longitudinal studies in which nutritional intervention is provided before cognitive decline occurs. http://ajcn.nutrition.org/content/71/2/614s.short
  46. David Caldero´n-Guzma´n et al., (2004) evaluated the effects of pyridoxine and butylated hydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxytryptophan and serotonin. Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-HTP. http://www.sciencedirect.com/science/article/pii/S0188440904000438
  47. Jonathan Benson (2013) write in naturalnews.com that chronic stress, poor diet, and certain medical conditions can deplete the body’s stores of vital nutrients,’ explains one source about the important of B vitamins. ‘Many of those who suffer from agoraphobia (fear of crowded spaces or enclosed public places) are deficient in certain B complex vitamins, and this may be the case for other anxiety-related conditions as well. Symptoms of vitamin B deficiency may include anxiety, restlessness, fatigue, irritability, and emotional instability. http://www.naturalnews.com/040563_vitamin_B_deficiency_panic_attacks_iron.html
  48. Pawle G et al., (2014) have investigated Antimicrobial, antioxidant activity and phytochemical analysis of an endophytic species of Nigrospora isolated from living fossil Ginkgo biloba. http://creamjournal.org/PDFs/Cream_4_1_1.pdf
  49. David O. Kennedy et al., (2000) investigated whether acute administration of Ginkgo biloba had any consistent effect on the four Cognitive Drug Research (CDR) factors in a clinical trial. Compared with the placebo, administration of Ginkgo produced a number of significant changes on the performance measures. The most striking of these was a dose-dependent improvement of the ‘speed of attention’ factor following both 240 mg and 360 mg of the extract, which was evident at 2.5 h and was still present at 6 h. Additionally, there were a number of time- and dose-specific changes (both positive and negative) in performance of the other factors. Acute administration of Ginkgo biloba is capable of producing a sustained improvement in attention in healthy young volunteers. http://link.springer.com/article/10.1007/s002130000501
  50. S. Kanowski et al., (1997) investigated the efficacy of the Ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the cognitive decline and multi-infarct dementia (MID). Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the cognitive decline type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated. http://www.sciencedirect.com/science/article/pii/S0944711397800219
  51. Zahoor Ahmad Shah et al., (2003) have investigated the effect of G. biloba on whole brain catecholamine, serotonin and plasma corticosterone levels following 1, 2 and 4 h restraint stress. G. biloba extract (14 mg/kg p.o.) restored restraint stress-induced elevation in whole brain levels of catecholamines (NE, DA), 5-HT and plasma corticosterone to near normal levels. Stress and depression and associated mental health problems have increased tremendously in modern times. The search for effective and safe alternatives from natural sources especially plant products should, therefore, continue. Forced immobilization is one of the best explored models of stress in rats and the role of corticosterone, serotonin and catecholamines, i.e. norepinephrine (NE), dopamine (DA) is well documented. http://www.sciencedirect.com/science/article/pii/S0924977X03000051
  52. G. S. Rai et al., (1991) assessed the effects of a standardized Ginkgo biloba extract (containing 24%flavonoid glycosides and 6% terpenes) on cognitive function in memory impaired patients. Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks. http://www.tandfonline.com/doi/abs/10.1185/03007999109111504
  53. J.-H. Heo et al., (2008) have examined the efficacy of Korean red ginseng (KRG) as an adjuvant therapy to conventional anti-dementia medications in patients with cognitive decline. The patients in the high-dose KRG group showed significant improvement on the ADAS and CDR after 12 weeks of KRG therapy when compared with those in the control group. The KRG treatment groups showed improvement from baseline MMSE when compared with the control group. Authors concluded saying KRG showed good efficacy for the treatment of cognitive decline. http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2008.02157.x/abstract
  54. T. Tode et al., (1999) have evaluated the degree of psychological dysfunction and levels of stress hormones in postmenopausal women with climacteric syndromes and effect of Korean red ginseng RG on them. Improvement of CMI and STAI scores in postmenopausal women suffering climacteric syndromes, particularly fatigue, insomnia and depression, by RG seemed to be brought about in part by effects of RG on stress-related hormones as shown by a decrease in CrD ratio. http://www.sciencedirect.com/science/article/pii/S002072929900168X
  55. Kwang-tae CHOI et al., (2008) reviewed Korean Panax ginseng and is mainly used to maintain the homeostasis of the body, and the pharmacological efficacy of Korean ginseng identified by modern science includes improved brain function, pain-relieving effects, preventive effects against tumors as well as anti-tumor activity, enhanced immune system function, anti-diabetic effects, enhanced liver function, adjusted blood pressure, anti-fatigue and anti-stress effects, improved climacteric disorder and sexual functions, as well as anti-oxidative and anti-aging effects. Oriental people have traditionally used ginseng roots and its extracts to revitalize the body and mind, increase physical strength, prevent aging and increase vigor. http://m.atkinsginsengfarm.com/Articles/aps2008134a.pdf
  56. Khaled Radad et al., (2006) reviewed Ginseng in Medicine With Emphasis on Neurodegenerative Disorders. Ginseng refers to the root of several species in the plant genus Panax (C.A. MEYER Araliaceae). Among them, Panax ginseng is the most widely used ginseng and is indigenous to the Far East countries (most notably China and Korea). Panax ginseng was first cultivated around 11 BC and has a medical history of more than five thousand years. https://www.jstage.jst.go.jp/article/jphs/100/3/100_3_175/_pdf
  57. Nora D. Volkow et al., (2009) evaluated biological bases that might underlie a reward/motivation deficit by imaging key components of the brain dopamine reward pathway (mesoaccumbens). Authors found a reduction in dopamine synaptic markers associated with symptoms of inattention was shown in the dopamine reward pathway of participants with attention deficit. http://jama.jamanetwork.com/article.aspx?articleid=184547
  58. Roshan Cools et al., (2011) reviewed evidence from a series of studies with experimental animals, healthy humans, and patients with Parkinson’s disease, which highlight two important factors that contribute to this large variability. First, the existence of an optimum DA level for cognitive function implicates the need to take into account baseline levels of DA when isolating the effects of DA. Second, cognitive control is a multifactorial phenomenon, requiring a dynamic balance between cognitive stability and cognitive flexibility. These distinct components might implicate the prefrontal cortex and the striatum, respectively. Manipulating DA will thus have paradoxical consequences for distinct cognitive control processes, depending on distinct basal or optimal levels of DA in different brain regions. http://www.sciencedirect.com/science/article/pii/S0006322311002782
  59. Nora D. Volkow et al., (1998) have assessed the relation between measures of brain dopamine activity and indexes of motor and cognitive function in healthy individuals. Age-related decreases in brain dopamine activity are associated with a decline in motor function and may also contribute to impaired performance on tasks that involve frontal brain regions. Interventions that enhance dopamine activity may improve performance and quality of life for the elderly. The fact that correlations remained significant after age effects were partialed out suggests that dopamine activity may influence motor and cognitive performance irrespective of age. http://ajp.psychiatryonline.org/doi/abs/10.1176/ajp.155.3.344
  60. H. C. Lou et al., (2008) examined the effect of phenylalanine restricted diet on vigilance, as judged by the continuous visual reaction times, and neurotransmitter synthesis, as judged by cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels in a group of 9 patients with classical phenylketonuria (PKU). In 14 patients on free diet supplemented with tyrosine, an improvement in vigilance (reaction times at the 90 percentile) was seen in all 12 patients with values longer than the normal mean (264 msec) (p<0.001). Tyrosine treatment may be a therapeutical alternative when phenylalanine restriction is impractical. http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.1987.tb10521.x/abstract
  61. Arnsten AF (2006) has reviewed the fundamentals of attention-deficit/hyperactivity disorder: circuits and pathways. Neuropsychological and imaging studies have shown that attention-deficit/hyperactivity disorder is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. The PFC is very sensitive to its neurochemical environment, and optimal levels of norepinephrine and dopamine are needed for proper PFCcontrol of behavior and attention. Recent electrophysiologic studies in animals suggest that norepinephrineenhances ‘signals’ through postsynaptic alpha2A-adrenoceptors in PFC, while dopamine decreases ‘noise’ through modest levels of D1-receptor stimulation. http://europepmc.org/abstract/med/16961424
  62. Una D. McCann et al., (1993) examined the effects of Catecholamine Depletion on Alertness and Mood in Rested and Sleep Deprived Normal Volunteers. The findings are consistent with the view that sleep deprivation is associated with decreased functional catecholamine neurotransmission. Furthermore, mood effects following sleep deprivation plus AMPT suggest that catecholamines may be involved in mood changes during sleep deprivation. http://www.nature.com/npp/journal/v8/n4/pdf/npp199334a.pdf
  63. Michael T. Heneka et al., (2009) have studied the Locus ceruleus controls cognitive decline. Research dating back to the 1960s implicated LC degeneration in the pathogenesis of cognitive decline. Of particular relevance, several studies show that AD patients present with a prominent loss of LC cells, reaching 70% within the rostral nucleus and causing reduction of cortical and limbic norepinephrine (NE) levels. http://www.pnas.org/content/107/13/6058.full.pdf
  64. S. Colette Daubner et al., (2011) studied regulation of dopamine synthesis. The biosynthetic pathway for the catecholamine neurotransmitters is explained. Phenylalanine hydroxylase converts phenylalanine to tyrosine, tyrosine hydroxylase hydroxylates tyrosine to L-DOPA and then to Norepinephrine. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065393/
  65. Arjan Blokland (1995) reviewed the acetylcholine involvement in learning and memory. The cholinergic hypothesis claims that the decline in cognitive functions in dementia is predominantly related to a decrease in cholinergic neurotransmission. This hypothesis has led to great interest in the putative involvement of the cholinergic neurotransmission in learning and memory processes. On basis of the available data, ACh seems to be more specifically involved in attentional processes than in learning and memory processes. http://www.sciencedirect.com/science/article/pii/016501739500016X
  66. E.K. Perry et al., (1995) studied Acetylcholine and Hallucinations – Disease-Related Compared to Drug-Induced Alterations in Human Consciousness. Newly proposed criteria for Lewy body dementia include alterations in consciousness. The traditional view that derangements of the basal forebrain cholinergic system in cognitive decline relate specifically to memory impairment is assessed in terms of a more general role for cortical acetylcholine in consciousness. This extends the concept that cortical acetylcholine enhances neuronal signal to noise ratio. It is suggested that muscarinic receptor activation in the cortex is involved in confining the contents of the discrete self-reported conscious ′stream.’ In the absence of cortical acetylcholine, currently irrelevant intrinsic and sensory information, which is constantly processed in parallel at the subconscious level, enters conscious awareness http://www.sciencedirect.com/science/article/pii/S0278262685712559
  67. Mirjana B Čolović et al., (2013) studied the Pharmacology and Toxicology of Acetylcholinesterase Inhibitors. Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/
  68. F. Bernardo Pliego Rivero et al., (1999) have investigated forskolin-induced expression of tyrosine hydroxylase in human foetal brain cortex. Brain-derived neurotrophic factor (BDNF) has previously been shown by this and other laboratories to work in concert with dopamine (DA) to induce the dopaminergic phenotype in foetal rat and human cerebral cortex during specified sensitive developmental stages. In the present study this induction by BDNF/DA was found to be greatly amplified by adding forskolin (fsk: 10 μM) to the rat and human cerebral cortex cultures together with DA (10 μM) and BDNF (50 ng/ml). Since fsk boosts intracellular levels of cyclic AMP (cAMP), its amplifying action when added together with BDNF/DA is likely to be due to interactions via the cAMP response element/cAMP response element binding protein (CRE/CREB) systems. http://www.sciencedirect.com/science/article/pii/S0165380699000346
  69. Susumu Ando et al., (1987) studied delayed memory dysfunction by transient hypoxia, and its prevention with forskolin. Rats were exposed to 40 min hypoxia 3 h before a one-trial learning passive avoidance task showed impaired memory retention 24 h later. This model was used to assess the ability of forskolin to restore the delayed memory dysfunction. Significant amelioration of memory retention was observed when forskolin (500 μg/kg, i.p.) was injected just after hypoxia. Forskolin is suggested to enhance cerebral blood flow and to facilitate memory function through the action of increased cyclic adenosine monophosphate (cAMP). http://www.sciencedirect.com/science/article/pii/0006899387903088
  70. JIANG Dai-xun et al., (2015) studied the prevention fMLP-induced neutrophils adhesion by luteolin via suppression of LFA-1 and phosphodiesterase 4 activity. Luteolin is an active ingredient found early from Folium perillae and Flos lonicerae, and has a specific inhibition on phosphodiesterase 4 (PDE4) activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP (cAMP), is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 (MAC-1) in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. http://www.sciencedirect.com/science/article/pii/S2095311914609047