Neuromelan®

A new approach to the prevention of Mild Cognitive Impairment (MCI) and

memory enhancement

Because remembering this face shouldn’t be a problem

“Long ago, in the childhood tale that we all know, Ali Baba’s secret words “open sesame” held the key to a gold mine. 300 years later, with the very same key, we have found a path to a golden mind.”

The Story of Sesame

An oldie but a goodie

Sesame (Sesamum indicum) is considered one of the oldest oilseed crops known to

human kinds. 3000 years ago, people have already domesticated sesame, and

harvested. Today, you probably see many of them in your favorite Asian or fusion dishes,

long since our ancestors’ time we have been enjoying this delicacy, but the real value of

this family “jewel” passed down from generations to generations have been overlooked

until now. It is not until recent decades that humans have begun applying modern

science on food products. These little gems are packed with nutritious values such as

minerals, proteins and other valuable goods.

Black is the new Black

In the fashion world “you can never go wrong with a little black dress”, well now the

same saying applies for the health food world. Recent advance in science has discovered

that the color of the skin of the food actually matters. There’s a new obsession over dark

skinned food which are packed with potent anti-oxidants with health benefits such as

anti-aging, reducing risk factor for heart disease and stroke and brain protection as

opposed to their lighter counterparts, this makes black sesame a superior candidate

than white sesame.

Black sesames are “armed” meaning they retain their shells. White sesames are hulled,

which means their shells are removed. Nutrition wise, of course the more the merrier.

With this new health trend that’s heating up, more and more food are put under the

microscope.

The shells of the sesame not only contain nutrition value such as higher calcium fiber

and etc… but most importantly it is packed with a secret ingredient melanin.

Melanin - the secret ingredient

Melanin is a group of natural pigments occurring in many organisms. The pigments are

derivatives of the amino acid tyrosine, however the pigment itself is neither an amino

acid nor a protein, and it is produced in melanocytes.

There are many types of melanin, Eumelanin, Pheomelanin, Allomelanin and

Neuromelanin. The predominant functions of melanin-like pigments in humans are

coloring of the hair, eye and gray matter of the brain. Studies have shown a deficiency

in these compounds may cause Parkinson’s or Alzheimer’s.

Neuromelan®

Neuromelan®, naturally derived from the shell of black

sesames harvested in the land bathed under the sun, with our

innovative advanced technique to extract melanin that are rich

in the reduced form.

Why Neuromelan®?

Sesame is very abundant. It can be adaptable to varieties of

soil and water conditions and can be easily harvested

In comparison to other “dark skin” counterparts sesame

hold the highest surface area to volume ratio Structure of Neuromelan®

We’ve selected double hulled black sesame, double the shell double the goods

Study indicates in comparison to other oxidative states, reduced pigment possess

the most antioxidant (Figure 1.)

Neuromelan® not only maintains its antioxidant properties post gastrointestinal

digestion, but also releases components that exert positive protective effect on basal

and induced oxidative stress

Other than its anti-oxidant activities, Neuromelan® showed marked binding

properties to heavy metals, may pose as a neurotransmitter and semi-conductor in

brain

Clinically proven to prevent the progression of MCI, and enhance memory function

Figure 1, Native or reduced sesame pigment inhibit LDL-oxidation; oxidized sesame pigment showed

almost no effect

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Mild Cognitive Impairment

“Mild cognitive impairment (MCI) is an intermediate stage between the expected

cognitive decline of normal aging and the more serious decline of dementia. It can

involve problems with memory, language, thinking and judgment that are greater than

normal age-related changes. ”- MAYO CLINIC

Most predominate symptoms of MCI are memory impairment and language.

Studies carried out in memory clinics suggests that 10-15 per cent of people with MCI

went on to developing a form of dementia per year. MCI represents a significant increase

for risk of developing dementia, roughly 3 to 5 times higher the risk than someone

without dementia.

There are 7 types of Dementia, but the most common type is Alzheimer’s which

accounts for 60-80% of the cases.

Every 68 seconds,

Someone in the United States develops Alzheimer’s!

YOU COULD BE NEXT

President Ronald Ragan, 6th year after his presidency he announced that he had Alzheimer’s and

promoted awareness for Alzheimer’s

Prevalence

1 in 3 seniors dies with Alzheimer’s or another dementia

In 2013, 15.5 million family and friends provided 17.7 billion hours of unpaid care to

those with Alzheimer’s and other dementias- care valued at $220.2 billion, 8 times

the total revenue of McDonald’s in 2012

It is estimated that 5.2 million Americans have Alzheimer’s disease, including

200,000 individuals younger than 65 of age with early onset of Alzheimer’s

By 2050, the estimated number of individual with 65 or older may triple, from 5

million to as many as 16 million

Alzheimer’s disease is the most expensive condition in the U.S.(est. $214 billion)

Mechanism of action

Alzheimer’s and other neurodegenerative diseases are defined by the progressive loss of

specific neuronal cell populations. Studies indicate that a common feature of these

diseases is the oxidative stresses that are responsible for dysfunction and death of

neuronal cells that contribute to this disease pathogenesis. Neurons are highly

vulnerable to free radical attack due to the following factors:

Low in Glutathione, a natural antioxidant that occurs in the body

High in polyunsaturated fatty acids in their membranes

Brain metabolism requires large amount of oxygen

Neuromelan® was treated under conditions mimicking the gastric and intestinal

digestion with alternating pH conditions, enzyme component as well as bile salts. A

cellulose dialysis tube was used to assess the serum availability of the components post

digestion, with the IN sample indicating material that enters the serum; the OUT sample

represents the component that remains in gastrointestinal tract. The experiment

indicates that even post digestion; not only does the pigment and soluble fraction

maintain its antioxidant activity, but also releases components that exert positive

protective effect on basal and induced oxidative stress. Among these metabolites, NMR

and LC/ESI(+)/MS analysis identified the key component as vanilic acid.

Figure 2, Reduction of DPPH by the mixtures obtained after digestion of the pigment.

Lipid Oxidation

Studies indicated an increased in Lipid Oxidation of Alzheimer’s patients. Neuron

membranes are packed with polyunsaturated acids. Unsaturated lipids are highly

susceptible to oxidative modification and lipid peroxidation. Lipid peroxidation is the

result of attacks by radicals on double bound of the unsaturated fatty acids thus

generating highly reactive lipid peroxy radical that initiate a chain of reactions that leads

to break down of products including 4-hydroxy-2,3-nonenal(HNE), acrolein,

malondialdehyde and F2-isoprostanes, each component which have been identified in

Alzheimer’s brain, cerebrospinal fluid or plasma.

In a study performed on vanlic acid, lipid peroxidation was monitored via TBARS through

male rat’s liver and brain. Results indicate the inhabitation activity not only exceed that

of vanillin but also significantly exceeded trolox (water-soluble analog of vitamin E,

which is a common anti-oxidant therapy used for Alzheimer’s) in brain tissue. To further

investigate the scavenge free radicals in cellular environment, intracellular ROS

evaluation was conducted via DCFH-DA fluorescent. Results indicating vanilic acid

inhibited ROS activity in BNLCL2 cells more strongly than Ascorbic Acid (another

well-known anti-oxidant a.k.a Vit. C) and Trolox.

Figure 3, Inhibition of lipid peroxidation, TBARS activities and intracellular ROS level by vanillin and

vanillic acid. (a) Inhibition of lipid peroxidation in Fe2+ ⁄ ascorbate system using liposomes as an

oxidizable substrate by the investigated vanillin, vanillic acid and the standard of AA. (b) After

treatment with vanillin, vanillic acid and trolox (20 lg ⁄ ml) with mice liver and brain homogenate, the

formation of malonaldehyde was determined by TBARS assay. (c) Changes in the intracellular ROS

level indicated by the DCFH-DA fluorescence intensity in BNLCL2 cells treated with the 20 lg ⁄ ml of

vanillic acid, AA and trolox. The intracellular ROS generation level of BNLCL2 cells was measured by

the DCFH-DA which is vanillic acid to detect produced H2O2 (0.1 mM). Each value is presented as

mean ± S.D. from triplicate independent experiments.

Heavy metals

Metals may serve as a catalyst in the generation of free radical, and themselves alone

may also act as an contributing factor to neurodegeneration.

Mercury is a common metal that occurs in fish, dental amalgam, vaccines and other

sources. Several studies measuring plasma and CSF concentration of metals in

Alzheimer’s that mercury was significantly higher in subjects with AD than healthy

controls.

Mercury is capable of increasing the prevalence of Alzheimer’s via different aspects of

the disease shown in Table 1. For example, rats exposed to mercury vapor four times a

day shown similar molecular changes as those in human brain cultures after 14 days.

Mercury is capable of inhibiting the binding of GTP which is necessary for neurotubulin

synthesis and several other cellular functions. Mercury has also shown to have synergic

effect with other metals such as Cadmium and Lead is capable of potentize mercury

effects.

Table 1. Overview of the effects of mercury found by in vitro studies and animal experiments

Neuromelan® has shown strong metal chelating activities both prior and post digestion,

it is capable of attenuating the synergic effect of Hg and Cd or Hg and Pb by binding to

Cd or Pb, as well as to binding to Hg directly, to further preventing the damage that

mercury causes for neurodegenerative disease.

Figure 4, Comparison of heavy metal chelating properties at pH 7.0 of black sesame pigment before

(black bars) and after (grey bars) the digestion treatment. Metal concentration= 15 µM, pigment

concentration= 0.05 mg/mL

Neuromelan® has not only demonstrated important radical scavenging activities

directly or via one of its metabolites vanilic acid in prevention of lipid oxidation, as well

as the binding activity to heavy metals, which act as an modulator/catalyst in the

pathology of Alzhemir’s disease.

Dopamine & Alzheimer’s

Current drugs on alzheimer’s mainly targets acetycholine however study indicates

dopamine the “feel good” nuerotransmitter is a feasible candidate.

Study indicated that Vanilic acid effect on DOPA oxidase activity in the B16F0 cells,

showed significant reduced celular DOPA oxidase activity by 87.5% and 96.7% more

sigfinacantly than common antioxidant Absoribic acid and arbutin.(Figure 5.)

According to figure 6, L-dopa oxidase depletes cell of L-dopa source which is a precursor

to Dopamine. Vanilic acid is capable of inhibiting L-Dopa oxidase activites, restore the

cell of its L-dopa resevior.

Study done in Germany recruited

elderly subjects and were given

dopamine precursor Levodopa and

tested them on meomry test. Post two

and six hours following participants

have memorized the given photos,

reaserchers have requested them to

recognize new images from old. After 2

hours, there was no difference in

memorization between L-dopa and

placeb group, however surprise finding

indciated that post 6 hours, the L-dopa

group was capable of memorzing 20%

more photo than controls. when

memories are encoded, certain images

take places at the synapses(nerve

ending) , this is only temporary (at 2

hour mark) only when dopmaine is

newly formed at the synapses, this can stablize the memories and retained over time as

opposed to short term synpase activation. This explain why no difference was noticed at

2 hour mark, but after 6 hour there was a long term, and subjects are capable of

learning and actully retain what they learned, and capable of keeping long term memory,

which is often a difficulty in Alzhemir’s patients.

Figure 6, L-dopa oxidation pathway.

Levodopa, though often a common L-DOPA supplement, however, side effects tends to

be servere. Common side effects include abnormal thinking, agitation, anxiety, clusiness

or unsteadiness, confusion, false sens of well being, hallucination and other unpleasent

cognitive and physical sensation.

Neuromelan® on the other hand, has none of those reported unpleasant side effects

and unlike direct ingestion of L-DOPA, it serves as a precursor to avoid these unpleasant

effects, and possess other cognitive protective activities.

Clinical Trial

A randomized double blind study with 134 patients of both sex between the ages of 51

to 81 years participated in a two year study.

Selected participants must pass the MoCA (Montreal Cognitive Assement Test) and

performed below the average result on a 6 subtest subjective complaint-test (LGT-3)

indicative for figural and verbal memory. The participants were divided into two groups,

and given placebo, and Neuromelan® (sesame) in the form of identical capsules.

Neuromelan® indicated no change in figural memory whereas placebo indicated a

progression in cognitive decline. (Figure 7.)

Neuromelan® indicated only a slight change in cognitive decline, placebo indicated a

substantial decline in cognitive function. （Figure 8.）

LGT-results between 40-60 are considered “normal range”. The overall percentage of

Lgt-results between 40-60 decreased by 15% in the placebo group. However, in the

Neuromelan® group, the population LGT score increased by 7%.

The result of the study indicated the effects of Neuromelan® are big enough to show an

apparent improvement in the overall study population.

FIGURE 7. CHANGE OF MEDIAN FOR THE SUBJECTIVE FIGURE 8. CHANGE OF MEDIAN FOR THE SUBJECTIV

COMPLAINT-TEST (Figural Memory) COMPLAINT-TEST (Verbal Memory)

FIGURE 9, Change in % of LGT score in the course of 24 months

of oral administration of Neuromelan®

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Sesame Natural Course (Placebo)

Safety

Neuromelan® is extracted from sesame at low temperature with water as solvent, the

processing is fully complies with the relevant requirements of Old Dietary Ingredients

defined in Dietary Supplement Health and Education Act of 1994（DSHEA）, therefore can

be used in dietary supplement as dietary ingredient without restriction in US.

Recommended Dosage

It is recommended to uptake 250 mg of Neuromelan® for adults per day.

Other beneficial effects

Semi-conductor

Aside from its amazing oxidation prevention functions, Neuromelan® proves to be

similar in structure with substantia nigra melanin. Studies indicate that they might be

involved in with transmitting and modulating nerve impulses, due to the fact that their

occurrence are scarce in new born babies (when movement isn’t fully developed) and

Parkinson’s (when movement isn’t controlled anymore), the correlation with motor

neurons are highly linked.

Eye protective effect

It has frequently been reported that ocular melanin protects the eye tissues, binding

heavy metals and trapping oxygenated free radicals. The lack of melanin in the eye

causes various problems (reduced visual acuity; nystagmus; strabismus; sensitivity to

bright light and glare). The most severe problem is found in the fovea, the small area of

the retina which permits acute vision, which does not develop completely because of the

lack of the melanin pigment which is needed for prenatal growth of the intraocular fine

structures and a normal pattern of nerves routes from the back of the eye to the brain.

Neuromelan®, as natural melanin pigment, could be a good dietary supplement for eye

health.

Hearing protective effect

It’s also reported people with albinism are at an increased risk for hearing impairment.

Melanin appears to play a role in the ability to hear properly and is important for the

overall function of inner ear canal. According to a 1994 study published in the journal of

"Pigment Cell Research," individuals who suffer hearing loss or are deaf lack adequate

melanocytes, which are cells found throughout body that are responsible for producing

melanin. According to the researchers, a lack of melanocytes in the inner ear results in

cochlear impairment, or hearing loss.

Prevention of cardiovascular disease (CVD)

A recent study suggested a beneficial effect of dietary black sesame meal on a reduction

in blood pressure in prehypertensive humans. It is likely that the antihypertensive effect

is due to decreased oxidative stress. Taken together with the absence of side effects, the

regular ingestion of dietary black sesame meal may be beneficial for CVD prevention in

individuals with prehypertension, or even those with hypertension. Therefore,

Neuromelan® is beneficial on prevention of cardiovascular disease (CVD).

Reference

1.Thomas Eidenberger,et al(2012).Black Sesame Pigment: DPPH Assay-Guided Purification, Antioxidant /Antinitrosating Properties

and Identification of a Degradative Structural Marker.J. Agric. Food Chem.,DOI: 10.1021/jf2053096 • Publication Date (Web): 16

Mar 2012

2.Tzung-Han chou, et al(2010). Antioxidative characteristics and inhibition of a-melanocyte-stimulating hormone-stimulated

melanogenesis of vanillin and vanillic acid from Origanum vulgare. Experimental Dermatology, 4 feb 2010.

3.Kevin J.Barnham, et al(2004).Neurodegenerative Diseases and oxidative stress. Nature Reviews, March 2004.

4.Yves Christen. Oxidative stress and Alzheimer disease. Am J clin Nutr,1 April 2014.

5.Farhana Zahir, et al(2005). Low dose mercury toxicity and human health. Enviornmental Toxicology and Pharmocology,17 May

2005.

6.Joachim Mutter, Alzheimer Disease: Mercury as pathogenetic factor and apolipoprotein E as a moderator.Neuroendocrinology

Letters, 4 Aug 2004.

7.Rumana Chowdhury. Dopamine Modulates Episodic Memory Persistence in Old Age.J.Neurosci,10 Oct, 2012

8.Jatuporn Wichitsranoi,et al(2011).Antihypertensive and antioxidant effects of dietary black sesame meal in pre-hypertensive

humans. Nutrition Journal, 10:82.

9.Bruno J. R. Nicolaus, A CRITICAL REVIEW OF THE FUNCTION OF NEUROMELANIN AND AN ATTEMPT TO PROVIDE A UNIFIED

THEORY

“In 2013, 15.5 million family and friends provided 17.7 billion hours of unpaid care to those with

Alzheimer's and other dementias – care valued at $220.2 billion, which is nearly eight times the total

revenue of McDonald's in 2012.” – Alzheimer’s association

Don’t let you or your loved ones be a burden to each other’s, start

PREVENTING TODAY!

The “Iron Lady”, Margaret Thatcher, one of the most influential politicians of all times, Thatcher died

on the morning of 8th April 2013 at a suite in The Ritz Hotel in London, because she was having

difficulty with stars at her Chester Square home due to brain decline of Alzheimer’s disease.