What Are the Benefits of Lemon Balm Leaf Extract?

1 Introduction to Melissa officinalis

Melissa officinalis L. (Melissa officinalis L.), also known as horse mint, monarda, American mint, long-leaved mint, wild bergamot, muna mint, lemon balm, bee flowers, and fragrant bee flowers. It is a perennial herb in the family Labiatae [Monarda] [1–2]. Plant height 60 cm–80 cm, stem 4-angled, many branched, leaves opposite, heart-shaped, evergreen throughout the seasons, both sides of the leaf sparsely pilose and with transparent glandular dots, with a strong lemon aroma. Flowers are terminal or axillary, small, with white or pale red corollas. The small nuts are long oval, shiny blackish brown, and the seed germination can be maintained for more than 4 years [3]. Melissa officinalis was considered by the ancient Greeks to be the embodiment of a god and was often used as an important aromatic herb in ancient Greek sacrifices [4].

More than 4,000 years ago, the Assyrians recorded the herb on clay tablets, which is the earliest record of the herb found so far. It is mainly divided into two families: Asian herbs and European herbs[5]. Its original habitat is the Mediterranean and Western Asia, and it is also found in the wild in central and southern China, southwestern China, and Taiwan Province[6].

2. Composition

Each 100 g of the edible part of Melissa officinalis contains 2.66 g of reducing sugar, 5.75 g of crude protein, 5.93 g of fiber, 1.2 mg of vitamin C, 0.24 mg of carotene, 806 mg of potassium, 309 mg of calcium, 149 mg of magnesium, 5.38 mg of iron, 0.97 mg of zinc, 1.5 mg of strontium, 0.75 mg manganese, 3.26 μg selenium, of which the potassium, calcium and selenium content is significantly higher than that of ordinary vegetables [7-8], and contains the following various organic compounds: aldehyde compounds such as citral, citronellal, nerol, geraniol, etc. [9]; terpene compounds such as citronellol, geraniol, linalyl acetate, linalool, tannic acid, α-pinene, β-pinene, β-caryophyllene, etc.[10-11]; phenolic compounds such as rosmarinic acid, caffeic acid and 3,4-dihydroxyphenyl lactic acid ester[12]; some natural flavonoids such as luteolin, luteolin-7-O-β-D-glucoside, apigenin-7-O-β-D-glucoside, apigenin-7-O-β-D-glucopyranoside, apigenin-7-O-β-D-glucuronide, apigenin-3' -O-β-D-glucopyranoside, Luteolin-7-O-β-D-glucoside-3-O-β-D-glucuronic acid, of which luteolin-7-O-β-D-glucoside-3-O-β-D-glucuronic acid is a new compound found in plants.

3 Pharmaceutical research

3.1 Sedative and soothing, anti-anxiety

Melissa officinalis extract can be used as a mild sedative or tranquilizer to combat anxiety. It has psycho-emotional improving functions and has been shown to effectively relieve stress [16]. Under appropriate stress, its ethanol extract has an anxiolytic effect in rats through chronic administration [17]. Studies have found that lemon balm extract is a potent inhibitor of γ-aminobutyric acid (GABA) transaminase [18]. GABA is an important neurotransmitter in the central nervous system that mediates inhibitory synaptic transmission. and is currently an important target for the pathogenesis of anxiety disorders and the development of new anxiolytic drugs. Rosmarinic acid (RA) can inhibit GABA transaminase and inhibit the degradation of GABA, thereby increasing the concentration of GABA in the brain, which has a sedative and soothing effect and can resist anxiety.

3.2 Improve cognition

Melissa officinalis extract also improves psychological and cognitive abilities. These mechanisms are currently thought to be related to muscarinic receptors and nicotinic acetylcholine receptors [19]. Melissa officinalis extract has acetylcholinesterase (AChE) inhibitory activity [20]. AChE inhibitors can achieve neuroprotective effects by inhibiting the activity of cholinesterase in the synaptic cleft, reduce the breakdown of acetylcholine, thereby increasing acetylcholine activity and achieving neuroprotective effects; Melissa officinalis extract also has a protective effect on the apoptosis of hippocampal primary neurons induced by methylenedioxymethamphetamine (MDMA), possibly due to its free radical scavenging properties and inhibition of monoamine oxidase (MAO), which can be used as a neuroprotective agent to prevent central nervous system diseases, suggesting its potential use in the prevention of neurodegenerative neurological diseases [21].

3.3 Antibacterial

The antibacterial properties of Melissa officinalis have also been demonstrated [22]. The ethanol fraction of Melissa officinalis has a very obvious antibacterial and preservative effect, and has a synergistic antibacterial effect with sodium nitrite, sodium benzoate and potassium sorbate [23]. Other components of the extract such as rosmarinic acid, caffeic acid and flavonoids are known to have antimicrobial activity against the following bacteria: Bacillus subtilis, Bifidobacterium, Clostridium, Escherichia coli, Klebsiella, Acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus rhamnosus, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella enteritidis, Shigella, Staphylococcus aureus, etc. are resistant, and fungi such as Candida albicans, Aspergillus niger, and Alternaria alternata are resistant [24].

3.4 Antiviral

Many studies have also shown that Melissa officinalis essential oil has antiviral properties, especially for herpes simplex virus types 1 and 2 (HSV-1, HSV-2). Mazzanti G (2008) found using virus binding experiments that Melissa officinalis extract does not prevent HSV-2 from invading host cells, so this mechanism may be used after the virus enters the host[25].

3.5 Anti-tumor and antioxidant

Its extract has an inhibitory effect on the proliferation of human colon cancer cells [26], and its volatile oil is very effective against a series of human tumor cell lines (A549, MCF-7, Caco-2, HL-60, K562) and mouse cancer cell lines (B16F10) [27]. It can scavenge DPPH free radicals and has extremely high antioxidant activity [28-29]. The antioxidant activity is related to phenolic compounds such as citronellal and nerol, as well as flavonoids. Melissa essential oil can be used as a natural fat-soluble antioxidant preservative for fatty foods and foods rich in fat [30].

3.6 Improves blood glucose tolerance

Melissa essential oil plays an important role in regulating blood glucose and blood lipids in mice with type 2 diabetes. It can enhance the blood glucose tolerance of patients with type 2 diabetes and significantly increase the level of insulin in the blood. The effect of Melissa officinalis essential oil in preventing high blood sugar is achieved by promoting the activity of GCK in mouse liver cells and inhibiting the activity of G6Pase and PEPCK in the cells. In the liver and adipose tissue, blood lipids are regulated by up-regulating the genes related to glucose metabolism, such as SREBP-1C, PPAR-γ and GLUT4.

SREBP-1C promotes the expression of genes related to fatty acid synthesis, and PPAR-γ activates the expression of genes that control the fatty acid metabolism of adipocytes, including those that encode lipid proteins and fatty acid transport proteins. These are common proteins that regulate fatty acid storage and glucose metabolism. Therefore, the plasma TAG concentration in the experimental group (essential oil treatment group) was significantly lower than that in the control group. In addition, since oxidative stress and reactive oxygen species lead to diabetes and its complications, patients with type 2 diabetes have elevated levels of free radicals in the body, reduced activity of antioxidant enzymes, especially glutathione peroxidase activity, and increased levels of lipid peroxides. When antioxidant nutrients such as Melissa officinalis essential oil are consumed appropriately, it may be beneficial to prevent or alleviate diabetes symptoms or complications [31].

3.7 Inhibit the formation of advanced glycation end products

Persistent hyperglycemia causes the body to accumulate advanced glycation end products (AGEs), which are deposited in neural tissue. AGEs modify cytoskeleton proteins, myelin proteins, and matrix proteins, etc., not only directly damaging neural structure and function, but also by enhancing oxidative stress, or by acting on the receptor for AGEs on the surface of neurons (RAGE), further leading to neurological dysfunction and complications. For example, recent studies have found that the concentration of RAGE in the serum of patients with early Alzheimer's disease (AD) is greatly reduced, and RAGE has been used as a biomarker for the diagnosis of AD. RAGE alone or in combination with AGEs inhibitors, antioxidants, soluble RAGE, etc. has shown great potential in preventing, alleviating, and reversing diabetic neuropathy. Some studies have found that Melissa officinalis L. ethanol extract can effectively inhibit the formation of AGEs. Therefore, Melissa officinalis L. ethanol extract, as an AGEs inhibitor, has shown its important role in reducing or alleviating chronic complications of diabetes [32].

3.8 Anti-adipose tissue formation

Adipose tissue formation requires adipocyte differentiation, angiogenesis and extracellular matrix remodeling, with angiogenesis often preceding adipocyte differentiation. Melissa officinalis fractionated extract can reduce the mRNA levels of angiogenic factors (VEGFs and FGF-2) and matrix metalloproteinases (MMP-2 and MMP-9) in adipose tissue, and increases the mRNA levels of angiogenesis inhibitors (TSP-1 and TIMPs). It has anti-angiogenic and MMP inhibitory activity, and can also inhibit the differentiation of preadipocytes into adipocytes, significantly reducing the increase in adipose tissue in obese mice of the same genotype, indicating that Melissa officinalis can prevent obesity as an angiogenesis inhibitor [33-34].

4 Summary

The pharmacological effects described above show the potential use of Melissa officinalis as an anti-tumor agent and sedative, and it has shown great potential in pharmaceutical development. For example, it is used in the clinical treatment of Alzheimer's disease (AD). In a small clinical trial, Melissa officinalis extract was shown to have a positive effect in the treatment of mild to moderate Alzheimer's disease (AD), improving cognitive and memory symptoms in patients with moderate to mild AD. A randomized controlled trial showed that patients taking Melissa officinalis for 4 months had better cognitive improvement than the placebo group.

Melissa can reduce agitation in patients with AD, which is consistent with its traditional efficacy in treating depression. In terms of side effects, there was no significant difference between the Chinese medicine group and the placebo group [35], however, in another randomized double-blind placebo-controlled trial, using the PAS (Pittsburgh Agitation Scale) and NPI (Neuropsychiatric Inventory) methods of assessment, there was no evidence to show that Melissa officinalis essential oil was superior to the placebo group and donepezil in the treatment of neuroexcitation in AD patients [36]. There are currently very few studies on this, the main pharmacological components are not well understood, and the methods of evaluating the efficacy of treatment vary, which contributes to the uncertainty about the efficacy [37]. Therefore, the development and utilization of its medicinal resources should be increased to make a greater contribution to the fight against disease.

References

[1]Liu Huichao, Jia Wenqing, Chen Yun. Tissue culture and rapid propagation of Melissa officinalis [J]. Anhui Agricultural Science, 2006, 34(19): 4882-4882.

[2]Li Dongxia. The use and cultivation techniques of Melissa officinalis [J]. New Countryside, 2006, (2): 14-14.

[3]Peng Quanyun. The elixir of life – Melissa officinalis [J]. New Rural Technology, 2005, (4): 27-27.

[4]Song Liang, Shen Guozheng, Fu Qiaojuan, et al. Overview of fragrant plants [J]. Hangzhou Agricultural Science and Technology, 2005, (6): 24-25.

[5]Rezwan Guli Mamat, Zhang Yanfu. A study of the name and nature of the Uyghur medicine Badranjibuya [J]. Chinese Journal of Ethnic and Folk Medicine, 2000, (4): 218-218.

[6]Chen Yinlong. Tissue culture and rapid propagation of Melissa officinalis [J]. Plant Physiology Newsletter, 2007, 43(3): 513-513.

[7]Lin Kaihe, Wu Lin. Lemon-scented specialty vegetable - Melissa officinalis [J]. Fujian Agriculture, 2004, (12): 19-19.

[8]Li Xianglan, Wang Limin. Cultivation technology of Melissa officinalis, a plant used for both medicinal and vegetable purposes [J]. Beijing Agriculture, 2004, (1): 3-4.

[9]Taherpour AA,  Maroofi  H,  Rafie Z,  Larijani  K. Chemical  composition analysis of the essential oil of Melissa officinalis L. from Kurdistan,  Iran  by  HS／SPME  method  and  calculation  of  the  bio－physicochemical   coefficients  of  the  components [J］. Natural Product Research，2012；26（2）:152－160.

[10]Meftahizade  H, Sargsyan  E, Moradkhani  H. Investigation  of  antioxidant capacity of Melissa officinalis L. essential oils[J］. Journal of Medicinal Plant Research，2010，4（14）:1391－1395.

[11]Meftahizade H,Lotfi M,Moradkhani H.Optimization of micro  propagation   and   establishment   of  cell   suspension   culture   in  Melissa  officinalis  L [J］.  African  Journal  of  Biotechnology， 2010，9（28）:4314－4321

[12]Weitzel  C,    Petersen   M.    Cloning   and   characterisation  of rosmarinic   acid   synthase  from    Melissa   officinalis    L  [J］. Phytochemistry，2011，72（7）:572－578.

[13]Patora  J,   Klimek  B.  Flavonoids  from  lemon  balm（Melissa  officinalis L.，Lamiaceae）[J］.Acta Pol Pharm,2002，59（2）: 139－143.

[14]Bahtiyarca  R.   The   essential   oil   of   Lemon  Balm （Melissa officinalis L.）， its components and using fields[J］.Journal of Faculty of Agriculture.OMU，2006，21（1）:116－121.

[15]Moradkhani H，Sargsyan E,Bibak H.Melissa officinalis L.，a valuable medicine plant:  A review[J］. Journal of Medicinal Plants Research，2010，4（25）:2753－2759.

[16]Kennedy  DO, Little  W, Scholey  AB, et  al. Attenuation  of Laboratory  －Induced     Stress      in      Humans     After      Acute Administration   of   Melissa   officinalis    （Lemon   Balm）[J］.

Psychosomatic Medicine，2004，66（4）:607－613.

[17]Ibarra A.Feuillere N.Roller  M,et  al.Effects of chronic administration of Melissa officinalis L. extract on anxiety－like reactivity  and  on  circadian  and   exploratory  activities  in  mice [J］.Phytomedicine，2010，17（6）:397－403.

[18]Awad R,  Muhammad  A,  Durst  T,  et  al. Bioassay－guided fractionation of lemon balm（Melissa  officinalis  L.）using  anin vitromeasure of GABA transaminase activity [J］. Phytotherapy Research，2009，23（8）:1075－1081.

[19]Kennedy DO,Wake G,Savelev S,et al.Modulation of Mood   and  Cognitive  Performance  Following  Acute  Administration  of   Single Doses of Melissa Officinalis（Lemon Balm） with Human   CNS Nicotinic and Muscarinic Receptor－Binding Properties[J］. Neuropsycho pharmacology ,2003，28（10）:1871－1881.

[20]Dastmalchi  K,   Ollilainen  V,   Lackman  P,   et  al.  Acetyl cholinesterase    inhibitory     guided     fractionation    of     Melissa officinalis L.[J］. Bioorganic ＆ Medicinal  Chemistry,2009，17 （2）:867－871.

[21]Hassanzadeh   G,      Pasbakhsh   P,      Akbari    M,      et   al. Neuroprotective  Properties  of  Melissa  Officinalis  L.   Extract Against  Ecstasy－Induced  Neurotoxicity[J］. 2011，13（1）:25 - 30.

[22]Nascimento F,  Locatelli J,  Freitas  C,  et  al. Antibacterial  activity  of  plant  extracts  and  phytochemicals  on  antibiotic -  resistant  bacteria[J］.2000，Brazilian  Journal  of  Microbiology, 31:247－256.

[22]Stanojevic  D,   Cv  omic  L,   Stefanovic  O,   et al. In vitro synergistic  antibacterial  activity  of Melissa  officinalis  L.   and some   preservatives  [J］.    Spanish    Journal   of   Agricultural Research，2010，8（1）:109－115.

[23]Anicic  NV, Dimitrijevic  S, Ristic  MS, et  al.Antimicrobial  activity of essential oil of Melissa officinalis L.，Lamiaceae[J］. Hemijska industrija，2005，59（9－10）:243－247.

[24]Mazzanti G,Battinelli L,Pompeo C,et al.Inhibitory activity of Melissa officinalis L.extract on Herpes simplex virus type 2 replication[J］.Nat Prod Res，2008，22（16）:1433－40.

[25]Encalada  MA,   Hoyos  KM,   Rehecho  S,   et  al.  Anti -  proliferative   Effect   of   Melissa    officinalis   on    Human   Colon  Cancer Cell Line[J］.Plant Foods for Human Nutrition,2011， doi:10.1007／s11130－011－0256－y

[26]Sousa AC,Gattass  CR,Alviano DS,et al.Melissa officinalis  L. essential oil:  antitumoral  and  antioxidant  activities  [J］.

[27]Journal  of Pharmacy and Pharmacology,2004，56（5）:677－681 Dastmalchi K,Damiendorman H,Oinonen P,et al.Chemical composition  and  in  vitro  antioxidative  activity  of  a  lemon  balm （Melissa  officinalis  L.） extract[J］.LWT－Food  Science  and Technology，2008，41:391－400.

[28]Mimica N,  Bozin  B,  Sokovic  M,  et  al. Antimicrobial  and  antioxidant  activities  of Melissa  officinalis  L.  （Lamiaceae） essential oil[J］.J.Agric.Food.Chem，2004，52，2485－2489.

[29]Lara MS,  Gutierrez JI,  Timón M,  et  al. Evaluation of two natural  extracts   （Rosmarinus  of  cinalis  L.   and  Melissa  of？ cinalis  L.）as  antioxidants  in  cooked  pork  patties  packed  in MAP[J］.Meat Science，2011，88（3）:481－488.

[30]Chung MJ,Cho SY,Bhuiyan MJ,et al.Anti－diabetic effects  of lemon balm  （Melissa officinalis）  essential oil on glucose-  and  lipid－regulating  enzymes  in  type  2  diabetic  mice[J］， British Journal of Nutrition,2010，104（2）:180－188.

[31]Miroliaei  M, Khazaei  S, Moshkelgosha  S, et  al. Inhibitory effects of Lemon balm  （Melissa  officinalis L.）  extract on the formation   of   advanced   glycation   end  products  [J］.   Food Chemistry，2011，129（2）:267－271.

[32]Yoon  M,  Kim  MY.  The  anti－angiogenic  herbal  composition   Ob－X  from  Morus  alba,   Melissa  officinalis,  and Artemisia  capillaris regulates obesity in genetically obese ob／ob mice[J］. Pharmaceutical Biology，2011，49（6）:614－619.

[33]Hong  Y,   Kim  MY,   Yoon  M.  The anti－angiogenic herbal extracts  Ob－X  from   Morus  alba,   Melissa  officinalis,   and Artemisia    capillaris    suppresses    adipogenesis    in     3T3 －L1 adipocytes[J］.2011，49（8）:775－783.

[34]Akhondzadeh  S,   Noroozian    M,    Mohammadi    M,    et  al. Melissa officinalis extract in the treatment of patients with mild  to moderate Alzheimer's disease :a  double  blind,randomised， placebo controlled trial[J］.Neurol Neurosurg Psychiatry,2003， 74（7）:863－866.

[35]Burns A，Perry E,Holmes C，et al.A double－blind placebo- controlled   randomized    trial    of   Melissa    officinalis    oil    and donepezil  for  the  treatment of  agitation  in  Alzheimer's  disease [J］.  Dementia  and  Geriatric  Cognitive  Disorders,  2011，31 （2）:158－164.

[36]Lee MS,Choia J，Posadzkib P，et al.Aromatherapy for health  care :An overview of systematic reviews[J］.Maturitas,2012， 71（3）:257－260.