A Brief Overview of the Effects of Melissa officinalis L. Extract on the Function of Various Body Organs

Abstract

Melissa officinalis (lemon balm) which belongs to the Lamiaceae family is a known herb that has long been used in traditional medicine to treat many disorders, and several studies have been conducted to identify the plant and its healing properties. The purpose of this article is to review a series of studies on the effects of the herb extract on the function of various body organs.
Due to its volatile organic compounds and active constituents such as terpenoids, flavonoids, quercetin, rutin, quercitrin, gallic acid and high antioxidant capacity, the extract of the plant can have a significant role in maintaining health and curing diseases.
In this paper data have been collected from books and scientific papers published in the databases like Science Direct, Web Science, Scopus, EBSCO, Iran medex and PubMed. Search in the interval of the years 2006 to 2012 was carried out. To search for the key words Melissa officinalis, lemon balm, and balm mint were used. About 80 articles was reviewed and after rejection non-related or similar items, in the end about 50 the number was actually cited.
Results indicate that the extract of the plant with its several antioxidant, anti- inflammatory, anti-pain, anti-spasmodic and anti-cancer properties as well as its cholinergic receptor activation have highly significant effects on improving behavioral symptoms, cognitive impairment, insomnia, anxiety, and stress.
However, these studies have been vast and sparse, and doing more focused and extensive researches in this area is recommended.

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Zahedan Journal of Research in Medical Sciences
Journal homepage: www.zjrms.ir
A Brief Overview of the Effects of Melissa officinalis L. Extract on the Function of
Various Body Organs
Ali Zarei,
1
Saeed Changizi-Ashtiyani,*
2
Soheila Taheri,
3
Nasser Hosseini
4
1. Young Researchers Club, Abadeh Branch, Islamic Azad University, Abadeh, Iran
2. Department of Physiology, Arak University of Medical Sciences, Arak, Iran
3. Education Development Center, Arak University of Medical Sciences, Arak, Iran
4. Department of Medicinal Plants, Faculty of Agriculture and Natural Resources, Arak University, Arak, Iran
Article information
Abstract
Article history:
Received: 17 Feb 2014.
Accepted: 12 Mar 2014
Available online: 2 Aug 2014
ZJRMS 2015 July; 17(7): 1-6
Melissa officinalis (lemon balm) which belongs to the Lamiaceae family is a known herb
that has long been used in traditional medicine to treat many disorders, and several studies
have been conducted to identify the plant and its healing properties. The purpose of this
article is to review a series of studies on the effects of the herb extract on the function of
various body organs. Due to its volatile organic compounds and active constituents such as
terpenoids, flavonoids, quercetin, rutin, quercitrin, gallic acid and high antioxidant
capacity, the extract of the plant can have a significant role in maintaining health and
curing diseases.
In this paper data have been collected from books and scientific papers published in the
databases like Science Direct, Web Science, Scopus, EBSCO, Iran medex and PubMed.
Search in the interval of the years 2006 to 2012 was carried out. To search for the key
words Melissa officinalis, lemon balm, and balm mint were used. About 80 articles was
reviewed and after rejection non-related or similar items, in the end about 50 the number
was actually cited. Results indicate that the extract of the plant with its several antioxidant,
anti- inflammatory, anti-pain, anti-spasmodic and anti-cancer properties as well as its
cholinergic receptor activation have highly significant effects on improving behavioral
symptoms, cognitive impairment, insomnia, anxiety, and stress. However, these studies
have been vast and sparse, and doing more focused and extensive researches in this area is
recommended.
Copyright © 2015 Zahedan University of Medical Sciences. All rights reserved.
Keywords:
Blood lipids
Liver
Antioxidants
Thyroid
Melissa officinalis
*Corresponding author at:
Department of Physiology, Arak
University of Medical Sciences,
Arak, Iran.
E- mail: dr.ashtiyani@arakmu.ac.ir
Introduction
edicinal plants have had a great role in
providing health and treatment as well as
disease prevention in human communities [1,
2]. Medicinal herbs are very rich in secondary metabolites
which have profound physiological effects on the function
of mammalian tissues in health and disease conditions [3,
4]. Melissa officinalis (lemon balm) is one of these known
herbs that has been used since a very long time ago for the
treatment of many illnesses like headaches,
gastrointestinal diseases, neurological diseases and
rheumatoid [5, 6]. M. officinalis from Lamiaceae family,
(Fig. 1), with other common names like bee balm, garden
balm, melissa, melissengeist, is a perennial herbaceous
plant which grows vastly from the central and southern
Europe to Iran and central Asia. It is also cultivated
worldwide for its edible properties [7-9]. This herb has
been used extensively in traditional medicine and the
history of it goes back to more than 2,000 years ago. The
plant has been used in a variety of ways from a sedative
and mild hypnotic drug [8-10], and reducing the heart
rate, antibacterial, antiinflammatory, antivirus,
antispasmodic, antioxidant, to a neurotherapeutic agent,
peripheral analgesic, as well as a binding agent to
cholinergic receptors [7, 11].
Avicenna, the Iranian eminent physician and
philosopher introduced this plant as vitality tonic and as a
sedative drug to treat neurological disorders [11].
Figure 1. Aerial parts of Melissa officinalis
The most important ingredients in the plant are known to
be phenolic compounds, rosmarinic acid, caffeic acid,
cholinergic acid, metrilic acid; flavonoids such as
luteolin, apigenin and monoterpene derivatives; the
sesquiterpenes including beta-caryophyllene and
M

Zahedan J Res Med Sci 2015 July; 17(7): 1-6
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germacrene; triterpenes such as oleanolic and ursolic acid;
volatile oil, and tannins [8]. The aim of present article is
to give a brief overview of the health benefits of M.
officinalis extract and is concentrated on the functions of
liver, thyroid, cancer, immune system, adipose tissue and
also plasma concentrations of some biochemical factors.
Materials and Methods
This review article is a survey of the empirical papers of
several authors who have examined the role of M.
officinalis extract in different body tissues. To conduct a
literature review, the authentic english sources in different
databases like Science Direct, PubMed, Google Scholar,
and Persian databases including: Scientific Information
Database (SID), Iran Articles Database of Medical
Sciences, Iran medex, Iranian Research Institute for
Information Science and Technology (Iran Doc), the
publications database (Magiran) and library archives, as
well as articles published in scientific journals, Persian
and English, have been used. Search in the interval of the
years 2006 to 2012 was carried out. To search for the key
words M. officinalis, lemon balm, and balm mint were
used. About 80 articles was reviewed and after rejection
non-related or similar items, in the end about 50 the
number was actually cited.
Results
The effect of M. officinalis extract on lipid profiles:
Hypertriglyceridemia is one of the most important factors
in the development of cardiovascular diseases [5]. Among
effective pharmacological agents in treating these
diseases, we can refer to statins, clofibrates and niacin.
However, in general these compounds are not effective in
reducing cholesterol concentration and are often
associated with adverse effects and drug toleration, [12-
19]. Therefore, all efforts have been concentrated on
prevention strategies like phytochemical diet.
According to recent studies, M. officinalis essential oil
has significant metabolic effects in vivo. Terpenoids are
among the essential compounds in herbal oils that induce
hypolipidemic effects by inhibiting liver biosynthesis and
formation of cholesterol nucleus in bile. Studies have
shown that the essential oil compounds of Plantago
asiatica inhibit mRNA and protein expression of HMG-
COA reductase in HePG
2
cells and C57BL/6 cells in rats
[19].
Although the lipid-lowering mechanism of M. officinalis
is not clearly known, studies have shown that regular and
daily drinking of M. officinalis tea may improve the
metabolic parameters like cholesterol and triglycerides in
humans [20]. In addition, M. officinalis has the potential
to inhibit hypercholesterolemia, to reduce serum lipid
concentrations and lipid peroxidation in the liver of
hypercholesterolemic rats [21]. Evidence show that herbal
oils, including M. officinalis oils have various
pharmacological effects which are mainly related to
volatile terpenoids such as geranial, cineol and caffeic
acid [5].
In a study on rats with hypercholesterolaemia, Changizi-
Ashtiyani et al. have shown that M. officinalis and
barberry extract can reduce serum cholesterol, low-
density lipoprotein (LDL) and triglyceride. However, the
hypolipidemic properties of alcoholic extract of M.
officinalis are more than those of barberry root which are
most likely related to the antioxidant properties of M.
officinalis and its effect on increasing thyroid hormone
[22].
Jun et al. in a study on the impact of M. officinalis
extract on reducing plasma triglyceride levels has shown
that this is due to the presence of quercetin compounds in
the plant and its possible effect on the inhibition of lipid
peroxidation [5].
M. officinalis essential oil also has anti diabetic
properties and improves glucose tolerance and adjusts the
expression of the genes involved in hepatic
gluconeogenesis studies by Chang et al. have shown that
daily uptake of M. officinalis at low doses can cause
hypoglycemia by increasing glucose uptake and its
metabolism in the liver, as well as by gluconeogenesis
inhibition [23].
Study of Zarei et al. on the effect of the M. officinalis
extract on the activity of liver enzymes in
hypercholesterolemic rats showed that the enzymes level
in hypercholesterolemic group receiving the extract
reduced [24]. Various reasons have been proposed for the
increase in liver enzymes in hypercholesterolemic rats.
For example one theory says that the accumulation of
lipids in the liver raises a pathological state causing
fibrous changes and eventually cirrhosis and hepatic
dysfunction. Following these disorders, levels of liver
enzymes, particularly ALT increases [25]. On the other
hand, hyperlipidemia will also stimulate the production of
free radicals [26].
The impact of M. officinalis extract on reducing liver
enzymes is known to be due to its powerful antioxidant
properties. This plant contains phenolic compounds,
which are among the most important antioxidant agents.
These compounds, especially flavonoids have a
protective effect on liver against damages caused by free
radicals because of their inhibitory effect on the
cytochrome system. Flavonoids can also protect the cells
against glutathione depletion by increasing the capacity of
the antioxidant enzymes (glutathione reductase, oxidase
and catalase) [24].
In another study, Bolkent et al. examined the effect of
M. officinalis extract on hyperlipidemic rats' liver in
which liver cholesterol, total lipid, lipid peroxidation, and
liver enzymes reduced while the glutathione levels
increased [21].
The effect of M. officinalis extract on the function of
pituitary-thyroid axis: The results of the study done by
Zarei et al. on the impact of M. officinalis extract on the
function of pituitary-thyroid axis in rats with
hypercholesterolemia showed increased thyroid hormone
levels and reduced levels of thyroid stimulating hormone
(TSH) [27]. Initially M. officinalis extract increases the
secretion of TRH and TSH and consequently it increases
the amount of T
3
and T
4
, this increase in T
3
and T
4
can

The effects of Melissa officinalis Zarei A et al.
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finally reduce TSH level through exerting a negative
feedback effect. Studies show that some neuromodulators
and neurotransmitters control the neurons which secret
TRH hormone in the hypothalamus. Some of these
neurotransmitters, such as catecholamines (epinephrine,
norepinepherine, serotonin and dopamine) have an
increasing role and some, such as interleukin-1 (IL
1
) and
gamma aminobutyric acid (GABA) have a decreasing role
[27, 28].
On one hand, the flavonoid compounds in the plant
preserve and conserve catecholamines by inhibiting the
monoamine oxidase enzyme (MAO) and on the other
hand, by inhibiting the cyclooxygenase enzyme, they
reduce the production of prostaglandins and inflammatory
cytokines in response to inflammatory stimuli. In this way
they can also exert their anti-inflammatory effects [29].
M. officinalis extract has two mechanisms on GABA: one
is its GABAergic property to inhibit GABA and the other
one is its cholinergic property which inhibits
acetylcholinesterase, and enhances the capabilities of
brain cholinergic receptors [27, 30].
According to studies, GABA inhibits and reduces TRH
secretion. So, if GABA is inhibited, TRH will increase
and subsequently the secretion of thyroid hormones will
increase too. Studies also indicate that the relation
between fat and leptin, is direct, but fats and thyroid
hormone levels have an inverse and significant relation.
Since M. officinalis extract can reduce blood lipid levels,
it is most likely that at least part of this effect is exerted
by increasing thyroid hormone [22].
Antioxidant effects of M. officinalis: M. officinalis has
powerful antioxidant effects and these effects probably
are exerted through the rosmarinic acid and the
benzodioxole present in the extract. The antioxidant
effects of these compounds are up to ten times stronger
than the effects of those of vitamins B and C. In this way,
Melissa officinalis, like vitamin C, can moderate the
neurotoxic effects of chemical drugs [7, 31].
In addition, compounds such as acid linoleic acid,
carnosic acid, urosolicacidare are also present in the
extract all of which have antioxidant properties.
M. officinalis compounds are able to bind to
acetylcholine; moreover, they contain an inhibitory effect
on the acetylcholinesterase (AChE) enzyme and thus are
able to improve cognitive functions like memory [32].
Pereira et al. has also shown that the antioxidant activity
of phenolic compounds in the plant extract is mostly
because of rutin, quercitrin, garlic acid, and quercetin.
The highest antioxidant properties of compounds belong
to quercetin and then to garlic acid, quercitrin and rutin
respectively. In this study it has been shown that
M. officinalis extract has a protective function against the
oxidative damage caused by different peroxidative agents.
These agents can cause lipid peroxidation in a number of
ways. Therefore, this herbal extract can inhibit the
production of chemically active species in their early
stages, or later, it may block lipid peroxidation through
various processes. Finally, the researchers state that
M. officinalis extract can prevent neurological diseases
associated with oxidative stress [33].
In another study, Martins et al. have tested the effect of
the M. officinalis extract on oxidative stress induced by
manganese (Mn). Manganese is an essential element for
biological systems, but its increased level may lead to
neurodegenerative diseases. Although the mechanism of
this neurotoxicity is not fully clear, the oxidative stress
has a key role in the development of these diseases. In this
study, it has been shown that that manganese increases the
level of thiobarbituric acid reactive substances (TBARS)
as a marker of oxidative stress in hippocampus and the
striatum. In that study the amount of the marker in
animals treated with the extract had decreased, too [34].
Analgesic and anti-inflammatory effects of Melissa
officinalis: Using herbs as pain relief has a long history in
the world of medicine. One of these plants is
M. officinalis whose analgesic effect is not dose-
dependent. The analgesic effect is likely done by opioid
receptors. Acute analgesic effect of this extract does not
differ much from that of morphine and aspirin. However,
its chronic analgesic properties are less than morphine and
aspirin. So, the peripheral analgesic function of the extract
seems to be less considerable than the central analgesic
mechanism [35].
The anti-nociceptive and anti-inflammatory effects of
M. officinalis are attributed to the rosmarinic acid and
flavonoids and terpenoids present in the extract. Probably
flavonoids have a more effective role by facilitating
prostaglandin synthesis. The analgesic activity of
flavonoids is through moderating opioidergic mechanism
[35, 36]
Drozd and Anuszewska have examined the effect of
M. officinalis extract on the immune system response in
rats. They have found that this effect is comparable to the
effect of levamisole, which is known for its effect on the
immune system. Aqueous extract of M. officinalis is
effective on both blood and cellular responses [37].
M. officinalis oil extract derived from the leaves of the
plant contains nerol (30.44%), citral (27.03%), isopolcule
(22.02%), cariophiline (2.29%), oxide carolyn (1.24%)
and citronella (1.06%). In animal models its clear and
strong anti-inflammatory and analgesic effects has been
shown in comparison to those of a standard analgesic and
anti-inflammatory drug (indomethacin) [38]. A
phytochemical study on M. officinalis suggests that
among its phenolic compounds, rosmarinic acid and galic
acid have the highest and the lowest concentrations
respectively [39].
Anxiolytic effect of M. officinalis extract: Anxiety
disorders are the most common mental disorders with the
prevalence of 10-30 percent. Results of several studies
indicate that the aqueous extract of M. officinalis with the
dose of 5 mg/kg has anxiolytic effect, whereas at higher
doses it has a sedative effect in rats. So, the anxiolytic
effects are dose dependent and may be applied through
opioid receptors [40].
In another study conducted to examine the effect of
traditional herbals on neurological disorders, including
Alzheimer's, epilepsy and depression, it is concluded that
the M. officinalis extract does not have any role in the
serotonin transport; however, it is involved in AChE

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activity. Moreover, M. officinalis extract has a moderate
affinity to gamma-aminobutyric acid receptor (GABA).
So it seems that the anxiolytic properties of M. officinalis
may be due to binding to GABA type receptors [41].
In some European countries, the herb extract is used as
pain reliever and relaxant especially when there is
disruption in the first stage of sleep by some unpleasant
stressful factors [42]. In another study on the effect of the
extract on people with Alzheimer's, it is found that M.
officinalis extract can reduce agitation in Alzheimer's
patients. The administration of the citronella, taken from
the extract, has caused sound sleep and has reduced
muscle tone in people with sleep and neurological
disorders. M. officinalis extract has also resulted in a
significant improvement in insomnia, irritability,
headaches, and heart disease in mentally ill patients [40].
Ibarra et al. study on the effects of chronic administration
of M. officinalis extract on anxiety reactions and circadian
activities has shown that the use of this extract reduces
anxiety like reactivities. Because the herb extract contains
significant amounts of rosmarinic acid, oleanolic acid,
ursolicacid, and triterpenoids, it is most likely that these
compounds inhibit GABA transport activity and increase
GABA level in brain [43, 44].
Akhondzadeh et al. study in which M. officinalis extract
was administrated to patients with mild to moderate
Alzheimer's for 4 months has shown a significant
improvement in their behavioral and cognitive symptoms
and a decrease in anxiety and apprehension. The
incidence of these effects is likely due to the stimulating
function of acetylcholine receptors present in the plant.
Similarly, Perry et al. confirm the healing effects of
M. officinalis on memory disorders which are due to its
cholinergic activity. In this respect, the plant is put in the
same rank as Gingo [45].
The effect of the extract on the nervous system:
Cerebral ischemia by causing metabolic disorders leads to
neuronal death. Researchers in a study on the effect of
M. officinalis on death inducing hypoxia, in cultured
cortical neurons in vitro and in the ischemic hippocampus
in vivo (rat hippocampus) have shown that using the oil
extract significantly protects neurons in hypoxia culture.
M. officinalis extract significantly decreases the activity
of caspase 3 and of TUNEL-positive cells (cells that are
located in the CA1 region of the hippocampus).
M. officinalis also inhibits the production of
malondialdehyde (MDA), and reduces antioxidant
capacity in hippocampus. mRNA levels of
proinflammatory cytokines, TNFX and IL
1
B and hypoxia
inducible factor-1α (HIF-lα) have shown a significant
increase after ischemia. The administration of
M. officinalis extract inhibits the expression of HIF-lα.
Studies have also shown that M. officinalis extract can be
used as a protective agent in several neurologic disorders
associated with cerebral ischemia [46].
Hassanzadeh et al. study suggests that the protective
effect of M. officinalis plant against apoptosis is resulted
from the impact of methylenedioxy-methylamphetamine
(MDMA) on nerve cells, part of which is probably
because of the removal of free radicals and amino oxidase
inhibitors. The in vitro study they conducted on neuronal
cells showed that daily use of M. officinalis extracts
within 3 weeks led to cell proliferation, neuroblast
differentiation and integration and increase of GABA
[47].
M. officinalis effect on Alzheimer's disease, seizures
and epilepsy: Alzheimer's disease is a degenerative
neurological disease which is believed to cause dementia.
Dementia is characterized by a progressive loss of
cognitive powers, which leads to social or occupational
disability [48]. M. officinalis has sedative and relaxing
effects and in its homogenate notably binds to brain from
nicotinic and muscarinic acetylcholine receptors and also
inhibits the effects of acetylcholine esterase enzyme.
Thus, by regulating the cholinergic system it is helpful in
Alzheimer's treatment and adjusting mood and cognitive
processes [7].
Epilepsy includes a group of disorders caused by
abnormal electrical activity in the brain. Epileptic attacks
may appear as seizure, convulsion, or other nervous
disorders (in sensory, cognitive, and affective functions).
The ingredients in M. officinalis plant imitate nicotine
effect in the body and accelerate starting time and
increases the duration of the attack. M. officinalis plant is
effective as a pretreatment in modulating the seizure
symptoms caused by the injection of pentylenetetrazol
(PTZ) in rats [48].
Anti tumor effects of M. officinalis extract: Saraydin
et al. studied the effect of M. officinalis extract on
cytotoxicity of breast cancer cell lines (MCF-7, MDA-
468, and MDA-MBA-231). The results showed that the
extract contained active cytotoxicity against all 3 cancer
cell lines. Protein expression of caspase-7 and (TUNEL)
positive cells in a group of rats treated with the extract
was much more than those of the control group, while Ki-
67 expression had reduced. In addition, in vitro studies
indicated that inhibition of tumor volume in the group
treated with the extract group compared to the control
group of rats reduced by 40%. Finally, we can say that M.
officinalis extracts has an anti tumor potential against
breast cancer [49]. de Carvalho et al. also showed that the
M. officinalis extract had anti mutagenic or antigeotaxis
properties [50]
.
Discussion
M. officinalis plant is one of the oldest and most known
herbaceous aromatic plants, and has been used in different
forms such as oil extracts, aqueous extract, and applying
ointment and compress. There are a variety of active
ingredients in the plant which make its antioxidant,
sedative, neuroprotective, anti-anxiety and hypnotic
properties possible. Its metabolic interventions occur
when the plant extract acts to protect the liver and reduce
the amount of lipid profiles and influence the thyroid
hormone function. The presence of active and effective
antioxidants, especial ability to inhibit the production of
free radicals, as well as cytotoxic and anti-mutagenic
effects, have given a unique feature to the plant. It seems
that this ancient medicinal herb has still enormous

The effects of Melissa officinalis Zarei A et al.
5
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potential that lies ahead of keen researchers to conduct a
lot of biological research.
Acknowledgements
The present article summarized and updated the latest
finding about Melissa officinalis. This was done as part of
the research project no: 90-123-12 in Arak University of
Medical Sciences. We would like to appreciate the kind
help we received from research deputy of the university.
Authors’ Contributions
All authors declare that they have no conflict of interest.
Conflict of Interest
The authors declare no conflict of interest.
Funding/Support
Arak University of Medical Sciences.
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Please cite this article as: Zarei A, Changizi-Ashtiyani S, Taheri S, Hosseini N. A brief overview of the effects of Melissa officinalis L.
extract on the function of various body organs. Zahedan J Res Med Sci. 2015; 17(7): 1-6.