Melissa Officinalis
Drugs

Author: giulia gamerro
Date: 14/02/2013

Description

introduction

Alternative name: Balm mint, blue balm, garden balm, honey plant, lemon balm, sweet balm, melissa officinalis.

Melissa officinalis is a perennial herb in the mint family Lamiacae. There are two subspecies, M. officinalis subsp officinalis, the common cultivated lemon balm, and M. officinalis subsp altissima, naturalized in New Zealand and known as bush balm. it is native of south Europe but it is grown all over the world, it is grown not only in herb gardens or to attract bees, but also in crops for medicine, cosmetics, and furniture polish manufacturing. It grows up to 100 cm, the leaves are lemon scent, the flowers are small white and pink and it smells tart and sweet like lemon. In Middle Ages lemon balm was steeped in wine to lift the spirits, help heal wounds and treat venomuos insect bites and stings. Then it was used to reduce stress and anxiety, promote sleep, improve appetite and ease pain from indigestion. Now a days it is known tha it has therapeutic effects, in fact it is one of the herbs included into the Ufficial Italian Pharmacopoeia. Lemon balm can be combined with other herbs, such as valerian or chamomile in order to promote relaxion.

composition

Although over 100 chemicals have been identified in Melissa officinalis. The main component are:
-essential oil: citral, citronellal, linalool, geraniol, β-caryophyllene-oxide
flavonoids
* phenolic acid
* terpenes
* rosmarinic acid
* caffeic acids
* tannins
* eugenol acetate

MEDICAL USES

HERPES

Extracts of medical plants are increasingly of interest as novel drugs of antimicrobial and antiviral agents. In 2008 Schnitzler’s group tasted the antiviral effects of lemon balm on herpes simplex virus1 and 2. They found that the 50% inhibitory concentration of balm oil for herpes simplex virus plaque formation was determined at high dilutions of 0.0004% and 0.00008% for hsv1 and hsv2 respectively. Plaque formation was significantly reduced with noncytotoxic concentration of lemon balm and high concentration of the oil abolished viral infectivity nearly completely. They also discovered that Melissa officinalis affected the virus before its penetration into the cells, that means Melissa inhibits the virus before absorption; in fact lemon balm is lipophilic and enable to penetrate into the cells.
In 2004 melissa officinalis was used in order to taste its antiviral activity on HEp-2 cells (infected by hsv2). They used different concentrations of the oil (25, 50, 100, 150, 200 microg/ml) and found that Melissa was non-toxic to HEp-2 cells up to a concentration of 100 microg/ml and it was slightly toxic at a concentration over 100. Melissa inhibited the replication of HSV.
Melissa officinalis oil affects infectivity of enveloped herpesviruses, 2008
Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2, 2004

There are different substances that can inhibit herpes viruses: rosmarinic acid and tannins.

- rosmarinic acid : Rosmarinic acid is an ester of caffeic acid and 3,4dihydroxyphenyllactic acid. It is commonly found in species of Boraginacaea, Nepetoidacaea and Lamiaceae. It has a number of biological interesting activities like antiviral, antibacterial, antiflammatory and antioxidant.
Rosmarinic acid, 2003

In 2012, in Germany was examinated an aqueous extract of Melissa officinalis, composed also by rosmarinic acid, for his antiviral activity. They found that when drug was added to the infected-cells no antiviral effect was observed, because Melissa and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner. More over the results demonstrated that rosmarinic acids was the main contributor to the antiviral activity of Melissa extract.
Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro, 2012

- tannins : Hydrolysable tannins (HTs), secondary metabolites widely distributed in the plant kingdom, are generally multiple esters of gallic acid with glucose. HTs have been shown to be effective antagonists against viruses, bacteria and eukaryotic microorganism.
antimicrobial and antiviral activity of hydrolysable tannins, 2008

In 2011 Lin’s group found that two hydrolysable tannins (chebulagic and punicalagin) inhibited HSV1 entry in noncytotoxic doses in A549 human lung cells. These tannins targeted HSV1 viral particles and they prevented binding, penetration and cell-to-cell spread. They targeted glycoproteins of the virus and they blocked polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. They block interaction between cell surface glycosaminoglycans and HSV1 glycoproteins.
Hydrolysable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread, 2011

CHLA and PUG inhibit HSV-1 entry by inactivating viral particles and preventing virus binding and internalization into A549 cells. (A) Viral inactivation assay. HSV-1 (104 PFU/ml) was mixed with CHLA (60 μM) or PUG (40 μM) for 1 h at 37°C and then diluted 50-fold (final virus concentration, 50 PFU/well) before infecting A549 cells. As a control, the same amount of virus was also mixed with the tannin, but diluted immediately and applied to the A549 cells. After a 48-h incubation period, viral plaques were stained and counted. DMSO (0.1%) was included as a negative control. The data shown are means ± the SEM of three independent experiments with each treatment performed in duplicate. (B) Viral attachment analysis using ELISA. Adherent A549 cell monolayers in 96-well plates were prechilled at 4°C for 1 h and then inoculated with HSV-1 (MOI = 5) in the presence of CHLA, PUG, or the DMSO (1%) and heparin controls at various concentrations for another 3 h at 4°C. Wells were washed to remove unadsorbed virus, subsequently fixed with 4% PFA, and then blocked with 5% BSA. ELISA was performed with a primary polyclonal rabbit anti-HSV-1 antibody (1:7,500) and a secondary goat anti-rabbit IgG conjugated with HRP (1:100,000), followed by development with TMB substrate and reaction termination with 1 M H3PO4. The absorbance was immediately determined at 450 nm. Values are expressed as the fold change of absorbance relative to the mock infection control (cells + 1% DMSO), which is indicated by the dashed line. The data shown are means ± the SEM of three independent experiments with each treatment performed in triplicate. © Viral binding assay using flow cytometry analysis. Dissociated A549 cells were infected with HSV-1 (MOI = 1) in the presence or absence of 60 μM CHLA or 40 μM PUG for 3 h at 4°C. Cells were then washed, blocked, and stained with FITC-conjugated polyclonal rabbit anti-HSV-1 antibody (1:500). Stained samples were washed and fixed with 1% PFA before being subjected to standard flow cytometry analysis. DMSO (0.1%) was used as a negative control, and heparin (100 μg/ml) was included as a positive control. Color indication for different treatments: gray, mock + DMSO; red, HSV-1 + DMSO; blue, HSV-1 + CHLA; green, HSV-1 + PUG; and purple, HSV-1 + heparin. The data shown are representative of three independent experiments. (D) Viral penetration analysis by plaque assay. A549 cells were prechilled at 4°C for 1 h before inoculation with HSV-1 (100 PFU/well) for 3 h at 4°C. The cells were then treated in the presence or absence of CHLA (60 μM), PUG (40 μM), or heparin (100 μg/ml) and further incubated for an additional 20 min with the temperature shifted to 37°C to facilitate viral penetration. At the end of the incubation, extracellular virus was inactivated by citrate buffer (pH 3.0) for 1 min and then washed with PBS twice before overlaying with medium. After 48 h of incubation at 37°C, viral plaques were stained and counted. DMSO (0.1%) was included as a negative control. The data shown are means ± the SEM of three independent experiments with each treatment performed in duplicate

They also found that antiviral activity was diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate.

INSOMNIA AND ANXIETY:

Several studies show that melissa officinalis helps to reduce anxiety and promotes sleep, especially when it is combined with other herbs like valerian, hops and chamomile.
In 2006 the efficacy and tolerability of a combined valerian and lemon balm preparation was investigated in a open multicenter study with children suffering from restlessness and nervous dyskoimesis. A convincing reduction was found for all the symptoms (restlessness and dyssomnia reduced from severe-moderate to mild or assent), the 80.9% of the patients with dyssomnia and the 70.4% with restlessness improved, and no study medication-related adverse events occurred.
A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children, 2006

in 2010 in a prospective study was shown that cyracos, a standardized Melissa officinalis extract, inhibits anxiety and insomnia. It reduced anxiety manifestation by 18% (p<0.01) amiolarated anxiety-associated symptoms by 15% (p<0.01) and lowered imsomnia by 42% (p<0.01). 75% of patients achieved full remission anxiety, 85% for insomnia, 70% for both.
Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances, 2011

Anxiolytic plants may interact with either glutamic acid decarboxylase (gad) or GABA transaminase (GABA-T), so it influences brain GABA levels and neurotrasmission. The aqueous extract of Melissa officinalis exhibites the greatest inhibition of GABA-T activity.
Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system, 2007

COGNITIVE FUNCTION:

Methanolic and aqueous extracts of Melissa officinalis have protective effect on hydrogen peroxide induced toxicity in PC2 cells and have radical scavenging properties. The methanolic extract is more effective. Neuroprotective and neurological properties of Melissa officinalis, 2009

Aromatherapy with essential oil of Melissa officinalis is a safe and effective treatment for clinically significant agitation in people with severe dementia, with additional benefits for key quality of life parameters. In a trial with 72 people (71 completed the trial), people were randomly assigned to aromatherapy or to placebo, then changes in clinically significant agitation and quality of life were compared between the two groups. No significant side effects were observed. 60% of treatment group and 14% of placebo group experienced a 30% reduction in clinically agitation. Also quality of life improved significantly.
Aromatherapy as a safe and effective treatment for management of agitation in severe dementia: the results of a double-bind, placebo-controlled trial with melissa, 2002

Melissa officinalis can be used in Alzheimer’s disease because it is useful in agitation for it has sedative effects. Several trials demonstrated that Melissa extract is of value in the management of mild to moderate Alzheimer’s disease and has positive effects on agitation in these patients. These effects are believed to involved muscarinic and nicotinic acetylcholine receptors (lemon balm has human CNS nicotinic and muscarinic receptors-binding property). Moreover Lemon balm showed high acetylcholinesterase and butyrylcholinesterase co-inhibitory activities.
The use of herbal medicine in Alzheimer's disease-a systematic review, 2006
Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double bind, randomised, placebo controlled trial, 2003
Modulation of mood and cognitive performance following acute administration of single dodes of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties, 2003.
Inhibition of cholinesterase by essential oil from food plant, 2012

GASTROINTESTINAL FUNCTION

Melissa officinalis has relaxant, sedative and spasmolytic effects. It was demonstrated that in rat isolated ileum it inhibits the response to KCl, Ach and 5-HT. Moreover it was found that the herbal formulation of ColiMil (Matricaria, Foeniculum, Melissa) is effective in the treatment of breastfed colic in infants, and it reduces upper gastrointestinal motility in mice, with a major contribution by Matricaria and Melissa. Furthermore an herbal combination of Taraxacum Officinale, Hipericum Perforatum, Melissa officinalis, Calendula officinalis and Foeniculum volgare was used in order to treat chronic non-specific colitis, the consequences were that palpable pains along the large intestine disappeared, defecation become daily in patients with obstipation syndrome, and defecation was normalized in patients with diarrhea syndrome.

relaxant effect of essential oil of Melissa officinalis and citral on rat ileum contractions, 2003
Effects of the herbal formulation ColiMil on upper gastrointestinal transit in mice in vivo, 2007
Treatment of chronic colitis with an herbal combination of Taraxacum officinale, Hipericum Perforatum, Melissa officinaliss, Calendula officinalis and Foeniculum vulgare, 1981

INTERACTION WITH THYROID

Melissa officinalis contains antihormonal components that inhibits both extrathyroidal enzymic T4-5’-deiodination to T3 and the T4-5’-deiodination. The active principles exhibits chemical characteristic of phenols or phenolcarboxylic acids: rosmarinic acid and ellagic acid are active inhibitory componentes.
It was discovered that a freeze-dried aqueous extract of different herbs included Melissa (FDE) have the ability to inhibit many of the effects of exogenous and endogenous TSH on the thyroid gland, because it can inhibit the binding to human thyroid plasma membrane.
This action can be useful in the treatment of Grave’s disease. The thyroid-stimulating "immunoglobulin G"http://flipper.diff.org/app/items/info/1892: found in the blood of patients with Grave’s disease resemble TSH in their ability to bind to the thyroid plasma membrane and to activate the gland. The extract FDE, with its active principle and oxidized constituents with antithyrotropic activity, may interact with pathogenically important components of Graves’-IgG to inhibit their ability to bind to TSH receptors, as FDE do with TSH. The support of this is the structural similarity between Graves’-specific IgG and TSH itself.
Antihormonal effects of plant extracts: iodotyronine deiodinase of rat liver is inhibited by extracts and secondary metabolites of plants, 1984
Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine tyrotropin in human thyrod membrane, 1984
Extract and auto-oxided constituents of certain plants inhibit tje receptor-binding and the biological activity of Graves' immunoglobulins, 1985.

DOSES

pediatric:Lemon balm may be used topically in children to treat cold sores. Speak to your health care provider for appropriate dosage for the child's age.

adult:For difficulty sleeping, or to reduce indigestion, flatulence, or bloating, consult a knowledgeable health care provider for the specific dose to best fit your needs. Possible doses may be as follows:

*Capsules: Take 300 - 500 mg dried lemon balm, 3 times daily or as needed.
*Tea: 1.5 - 4.5 grams (1/4 - 1 teaspoonful) of dried lemon balm herb in hot water. Steep and drink up to 4 times daily.
*Tincture: 60 drops of lemon balm daily
*Topical: Apply topical cream to affected area, 3 times daily or as directed.
For cold sores or herpes sores, steep 2 - 4 teaspoonfuls of crushed leaf in 1 cup boiling water for 10 - 15 minutes. Apply tea with cotton balls to the sores throughout the day.

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