An Overview on Peppermint Attenuating Amyloid β Level in Alzheimer’s Disease

There is no proven way to prevent Alzheimer’s disease (AD). No pharmacon,

vitamin, over the counter remedy, or cognitive training has been clinically proven to

treat the brain disease that accounts for sixty to eighty percent of dementia cases. Alzheimer’s

disease is a progressive neurodegenerative disease that impairs memory and other important

functions vital for cognition. According to the Alzheimer’s Association, in the current world

population, AD affects approximately 5.5 million people in the United States alone, and an

estimated 5.3 million are over the age of 65. This number is expected to triple by 2050. Not to

mention, by 2050, Alzheimer’s and other dementias are expected to cost the nation as much as

1.1 trillion dollars (“Latest,” 2017). Dementia is a general term for disorders of the mental

processes, with AD being the most common type. Other types include: Parkinson’s disease,

Huntington disease, and Vascular dementia. Peppermint, an essential oil known for its profound

cognitive advantages in a normal brain, can translate its inherent beneficial effects on memory to

an Alzheimer’s brain, through interaction with amyloid plaques.

The major neuropathological signs of AD are amyloid plaques and neurofibrillary

tangles. The plaques consist largely of the microscopic protein fragment beta-amyloid (Aβ or

Abeta), which is produced by a large membrane protein called amyloid precursor protein (APP),

that plays a significant role in the neuronal growth and repair processes. When APP is activated

to perform its normal duties, it is cut by other proteins into separate sections that stay inside

cells. APP can be cut in a variety of ways, however, under some irregular circumstances, one of

the pieces produced from the cut is beta-amyloid. The beta-amyloid, with its glutinous tendency,

accumulates in the brain and disrupts communication between brain cells, ultimately killing

them. Amyloid plaques – large accumulation of Aβ – is a hallmark not only in Alzheimer’s

disease and dementias associated with Parkinson’s disease and Huntington’s disease, but also in

traumatic brain injuries. While the underlying cause of AD is yet to be discovered, some

researchers believe that the flaws in the processes regulating production or the disposal of beta-

amyloid are the primary cause of AD. Scientists are testing a number of strategies to hinder the

effects of beta-amyloid. Several drugs have been tested, but there has been no clear indication

that these drugs moderated Alzheimer’s brain changes. In addition to this, scientists have

explored drugs that center on preventative treatment. Due to some studies that suggest that the

toxic effects of beta amyloid occur before the formation of plaques, researchers have focused on

preventing the initial interactions beta-amyloid and neurons. Neurons are essential for storing

memories and processing thoughts and emotions; thus, the erosion obstructs learning and

memory.

The herb peppermint, has been used in Ancient Egyptian times dating back to 1000 B.C.,

when it was valued as a remedy for indigestion. During the eighteenth century, peppermint

became popular among the Western Europeans as a means for curing nausea, vomiting, morning

sickness, and respiratory infections. In modern times, it appears in the British Herbal

Pharmacopoeia as a treatment for intestinal colic, borborygmi, colds, morning sickness, and

menstruation pain. Science continues to expand the list of conditions that can be treated by the

use of peppermint. Peppermint (Mentha Piperita) is a hybrid mint, a cross between spearmint

(Mentha Spicata) and watermint (Mentha Aquatica) cultivated in Europe and North America

(“Mentha,” 2014). The major components of peppermint oil, which were previously reported by

Clark and Menory (1980), include menthol (29–48%), menthone (20–31%), menthofuran (6.8%)

and menthyl acetate (3–10%) representing nearly 90% of the total essential oils. These individual

constituents enter the body through two different pathways. Since these essential oil constituents
can cross the blood/brain barrier, they can exert effects on the brain/CNS by being absorbed into

the blood stream through the skin, the tissues of the respiratory system, or the gastrointestinal

tract (when taken internally). This is how conventional drugs used in the treatment of

neurological and psychiatric problem normally work. In inhaling the essential oil, the

constituents of that oil bind to and activate olfactory receptor cells in the nose. These activated

receptor cells then send signals down the olfactory nerve and those signals travel to the limbic

system and other areas of the brain that are involved in emotional response and memory as well

as endocrine and immune system responses. There are currently no conventional drugs that

utilize this pathway. The “peppermint essential oil” does not produce any effects on the body,

rather it is the menthol, menthone, and other constituents that make up the “peppermint essential

oil” that produce the effects. This fact is often overlooked by researchers who are investigating

the effects of essential oils.

Studies have been conducted to evaluate the components of peppermints effects on

amyloid plaques. These promising nutraceuticals offer remarkably few, if any, side effects

because of their natural configuration, and may greatly aid in the managing of brain senescence.

Current Research on Constituents of Peppermint

1. Rosmarinic Acid

Rosemary along with peppermint has a long history of ancient use for illness.

Rosmarinic acid, a polyphenol antioxidant carboxylic acid found in rosemary and

Lamiaceae herbs, such as peppermint, is shown to have antiviral, antibacterial, and

anti-inflammatory properties. In addition to being potent in these areas, recent

research has shown that romarinic acid protects brain cells from Abeta toxicity

(Pizzorno, n.d.).
 An in vitro study done at the University of Naples, Italy, “demonstrated the

neuroprotective effect of rosmarinic acid on rat neurons exposed to the toxic effects

of Abeta” (Pizzorno, n.d.). The acid reduced DNA fragmentation, tau

phosphorylation, and reactive oxygen species formation – all in which are major

factors in AD. With the conclusion of their results, the researchers determined that the

rosmarinic acid (found in peppermint) validated the use of the acid in patients

suffering from mild to moderate AD because it “exerts neuroprotective, ant oxidative,

and anti-apoptotic effects against Abeta insult” (Pizzorno, n.d). The researchers

deemed that rosmarinic acid “could be a key molecule for the development of

therapeutics for Alzheimer’s disease.” The acid not only prevents the toxicity of

Abeta to brain cells, but it has also been found to inhibit Abeta formation.

2. Luteolin: a yellow crystalline flavonoid

Luteolin (Lu) is widely distributed in plant families, including peppermint. Lu

possesses a variety of pharmacological activities, including antioxidant, anti-

inflammatory, antimicrobial, anticancer, and neuroprotective activities (Ansari and

Niloufar, 2013-7). It has been shown that Lu effectively attenuated tau hyper

phosphorylation, down regulated the expression of APP, and lowered the secretion of

Aβ (Liu et al., 2011). In addition to this, Lu “enhanced neuronal cell survival with

efficacy higher than and potency similar to vitamin E, in ROS-insulted primary

neurons (Liu et. al, 2011). Lu also activated Nrf2 pathway and induced ERK1/2

activation in neuronal cells (Wruck et al., 2007).

3. Menthol

Menthol, a well-known component of peppermint, “provided significant protection in

aged and beta-amyloid protein-treated mice against cognitive decline (“Powerful,”

2013). Menthol is known to be readily available, safe, and inexpensive to use. The

researchers reported that the menthol administered for 10 days significantly improved

spatial learning and memory. Menthol also “reversed the amnesia induced in animals

upon treatment with beta-amyloid on the 10th day” (Bhadania et al., 2012).

Pretreatment with menthol showed an increase in glutathione content, reversing the

increased oxidative stress seen in animals not pretreated with menthol (“Powerful,”

2013). The researchers stated that a “higher dose of menthol also improves the brain

function through decrease in malondialdehyde level [lipid peroxidation product] in

aged and beta-amyloid treated mice. Lower dose of menthol (100 mg/kg s.c.) showed

improvement in spatial working memory as compared to higher dose” (Bhadania et

al., 2012). This experiment was done by subcutaneous injection; therefore, inhalation

was not determined. However, oral intake is still directly absorbed by the nasal

mucosa and efficiently transported to the brain.

4. General Functional Ability of Peppermint

The extracts of 27 vegetables and spices and herbs (including peppermint) were

screened for their functional ability to inhibit the aggregation of islet amyloid

polypeptide (IAPP, amylin) into toxic amyloid aggregates (“Amyloid Antagonist,”

n.d.). This study states that peppermint “emerged as possessing the greatest anti-

amyloid activity” (“Amyloid Antagonist,” n.d.).

 Studies have been conducted to evaluate peppermint’s documented effects on various

gastrointestinal and neurological conditions such as dyspepsia and tension headaches.

Peppermint’s antispasmodic and antidiarrheal effects are topics of continued research in the

modern era. In the 1990s, researchers at the university of Cincinnati found that even a whiff of

peppermint helped test subjects perform better on tasks that required sustained concentration.

This is turn, prompted schools and teachers to participate in this phenomenon. In 2007, “The

Washington Post” reported that more and more schools were encouraging students to eat

peppermint candy to help boost test scores. The smell and flavor of peppermint could have a

significant effect on the cognitive abilities of not only these test takers, but also patients with

AD. A study published in “International Journal of Neuroscience” in 2008 found that participants

exposed to peppermint oil experienced enhanced memory and processing speeds (Mark, Moss et

al., 2005). Zoladz and Raudenbush (2005), two psychology professors, examined the effects of

scents on cognition and found a task-dependent relationship between scent and the enhancement

of cognitive processing. For example, cinnamon’s scent improved participants’ scores on tasks

related to attentional processes, virtual recognition memory, working memory, and visual-motor

response speed. This research suggests that certain scents have the ability to increase cognitive

performance (Zoladz and Raudenbush 2005). Similarly, Moss, Hewitt, Moss, and Wesnes (2008)

examined scent-influenced cognitive performance and showed that peppermint scent enhanced

memory whereas ylang-ylang, an essential oil deriving from the cananga tree, both impaired it

and lengthened associated with processing speed (Mark, Moss, et al., 2005). The results of a

study focusing on investigating the effects of spearmint on age-associated memory impairment

suggests that the spearmint extract might be a beneficial intervention for cognitive health. The

study’s subjects showed a significant improvement of spatial and working memory after the
implementation of spearmint extract as opposed to placebo. The supplementation was by

ingestion (Herrlinger, Kelli A., et al., 2018). Since peppermint affects the memory and cognition

of the human brain effectively in this manner, there is reason to believe it could help those with

neurodegenerative diseases positively through interaction of proteins.

Further research solidifies peppermint’s interaction with proteins. In 2009, a study at UC

Davis reported a connection between amyloid plaques and bacteria. The research suggested that

the brain characterized the hard-insoluble plaques known as amyloid plaques as bacteria.

“Alzheimer’s disease may be a case of mistaken identity,” said Andreas Bäumler, a professor of

microbiology and medical immunology. He continued to say: “our results suggest that it’s the

structure of these protein aggregates that matter and that, to the innate immune system,

Alzheimer’s plaques may look like colonies of bacteria. This would result in the chronic

inflammation we see in Alzheimer’s disease that damages neurons.” (UC Davis). Distinctive

chemical components of plants protect them from insects, bacteria or viruses that cause diseases.

Essential oils prepared from plants, therefore, may be effective in protecting humans from viral

infection. In addition to their intrinsic benefits to plants and as fragrances for people, essential

oils have been used throughout history in many cultures for their medicinal and therapeutic

benefits. The antibacterial activity of different extracts of peppermint against bacterial strains

was investigated in a study by Singh et al. The study found that the concentrations of the

essential oil inhibited the growth of microorganisms. They used multiple types of bacteria

including Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli. Staphylococcus

aureus is the leading cause of skin and soft tissue infections, frequently found in the nose,

respiratory tract, and on the skin. Streptococcus pyogenes is clinically important in human illness

and is highly contagious. This bacterium typically grows in pairs or chains and is responsible for
hundreds of millions of illnesses each year. Escherichia coli are bacteria found in the

environment, foods, and the intestines of humans and animals. Some E. coli normally live in the

intestines of humans, also known as “normal flora” but some particular strands make people sick

and can become fatal. This indicates that peppermint, with its antibacterial properties, may be

able to positively react against the brains “bacteria” plaques and ultimately aid in the rectification

of the brain.

The main compounds of peppermint could potentially harness a short-term treatment for

Alzheimer’s and other forms of neurodegenerative diseases, such as dementia, CTE, and

Parkinson’s disease. The menthol present in peppermint serves as an active compound which

could inhibit the growth of bacteria, in this case, the amyloid plaques. When peppermint interacts

with the hard-insoluble amyloid plaques, it can proceed to break down the sticky buildup, thus

halting the deterioration of neurons. This allows the Peppermint to ultimately translate its

beneficial effects in order to terminate the manifestation of AD. In finding a cure for AD, which

is able to break down these insoluble plaques, AD will virtually be eliminated in society. AD,

which is currently the sixth leading cause of death in the United States, could be prevented,

cured, or even slowed a significant amount.

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