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Lemon balm (Melissa officinalis)


Melissa officinalis
Synonyms / Common Names / Related Terms
Balm, balm mint, bee balm, blue balm, Citra, citronellae, citronmelisse, common balm, cure-all, dropsy plant, English balm, folia citronellae, folia melissae citratae, garden balm, gastrovegetalin, hjertensfryd, honey plant, kneipp melisse pflanzensaft, Labiatae/Lamiaceae (family), lemon melissa, lomaherpan, melissa, Melissa officinalis, Melissa officinalis L., melissae, melissae folium, Melisse (German and French), melissenblatt, melissengeist, sweet balm, sweet mary, toronjil (Spanish), valverde boutons de fievre crème.




Mechanism of Action

Pharmacology:

  • Constituents: The known major components of lemon balm are reported to include hydroxycinnamic acid derivatives, particularly rosmarinic acid, caffeic acids, chlorogenic acid, and metrilic acid 26,27,5,22,18,28, tannins3,12,29,1,30, flavonoids, including luteolin, luteolin 7-O-beta-D-glucopyranoside, apigenin 7-O-beta-D-glucopyranoside, and luteolin 3'-O-beta-D-glucuronopyranoside25,8,20,19,21,16,31,32, monoterpene glycosides33, sesquiterpenes, including ß-caryophyllene and germacrene33, triterpenes34, and volatile oils, including citronellal, citral a (geranial), citral b (neral), methyl citronellate, ocimene, citronellol, geraniol, nerol, ß-caryophyllene, ß-caryophyllene oxide, linalool, and ethric oil35,20,19,36,37,38,39. The volatile oil comprises 0.5-0.1% of the plant by weight, and citronellal, geranial, and neral constitute about 50-70% of this oil.35 Eugenylglycoside has been isolated from lemon balm leaves.40 The chemical composition of lemon balm tea yielded 10mg/L of essential oil (74% citral) and large amounts of polyphenol compounds.41 Steam distillates of lemon balm callus cultures yielded dehydroabietane and another diterpene hydrocarbon, with the relative proportion of those two compounds varying considerably during cultivation passage.42
  • Antiviral effects: Studies have reported that aqueous extracts of lemon balm exhibit antiviral effects against Newcastle disease virus, Semliki forest virus, influenza virus, myxoviruses, vaccinia, and herpes simplex virus.29,24,1,3,12,13 Lemon balm extract and rosmarinic acid have demonstrated antiviral properties against HIV-1.14 Studies conducted to assess the antiviral effects of lemon balm on Herpes simplex virus 1 have suggested that different extracts of the herb (M1, M2, M3, and M4) exhibit different effects on the virus.24 Studies conducted to assess the antiviral effects of lemon balm on Herpes simplex virus 2 suggest that the volatile oil components of lemon balm inhibit replication of HSV-2.43 Lemon balm's antiviral effects are attributed to the tannin and polyphenol constituents. Tannins are reported to possess antiviral properties29,1,12,3,13 as are rosmarinic, caffeic, and ferulic acids24,1.
  • Antibacterial/antifungal effects: The lemon balm constituent rosmarinic acid was reported to impair in vivo activation of mouse macrophages by heat-killed Corynebacterium parvum, as measured by the decreased capacity of the activated macrophages to undergo the oxidative burst.28 In vitro analyses of the antimicrobial properties of lemon balm suggested that at a concentration of 500microg/mL, the herb completely inhibits the growth of all yeast species including, Torulaspora delbrueckii, Zygosaccharomyces bailii, Pichia membranifaciens, Dekkera anomala, and Yarrowia lipolytica.23,44 Data from in vitro analyses have suggested that lemon balm may be effective as an antibiotic against anaerobic and facultative aerobic periodontal bacteria including, Porphyromonas gingivalis, Prevotella spp., Fusobacterium nucleatum, Capnocytophaga gingivalis, Veilonella parvula, Eikenella corrodens, Peptostreptococcus micros, and Actinomyces odontolyticus .45 Lemon balm oils have been reported to demonstrate highest activity against S. enterica (BA50 range, 0.0044-0.011%).46 Antibacterial activity was reported to be expressed on a multiresistant strain of Shigella sonei.47
  • Antiinflammatory effects: The paucity of clinical evidence makes the assessment of the antiinflammatory effect of lemon balm difficult to verify.28,48 Rosmarinic acid has been reported to reduce paw edema induced by cobra venom factor in rats and to inhibit passive cutaneous anaphylaxis in rats at doses of 1-100mg/kg by mouth. Rosmarinic acid has been reported not to inhibit t-butyl hydroperoxide-induced paw edema in the rat, indicating selectivity for complement-dependent processes.28
  • Antioxidant effects: In vitro data suggest that lemon balm contains high concentrations of antioxidants (greater than 75mmol/100g).6,2,8,27,5,49 Lemon balm has been reported to demonstrate high phenolics content and antioxidant properties (TEAC 4.06+/-0.31 mM/QE 1370.09+/-41.38 microM).50 Lemon balm extracts and rosmarinic acid have both been reported to demonstrate antioxidant properties in vitro27,2,5, and rosmarinic acid and caffeic acid have demonstrated significant antioxidant and immune modulating activities28,48,5,4. During linoleic acid autoxidation and its EDTA-mediated oxidation, lemon balm showed antioxidant activity.51 An in-vitro cytotoxicity assay demonstrated that lemon balm oil was very effective against a series of human cancer cell lines (A549, MCF-7, Caco-2, HL-60, K562) and one mouse cell line (B16F10). Further antioxidant activity of lemon balm has been reported as evidenced by the reduction of 1,1-diphenyl-2-picryl-hydrazyl (DPPH).52 Studies have demonstrated that the cytoprotective effect of lemon balm extracts seen in rats was due in part to free-radical scavenging properties.8,4 Immunostimulating effects of a lemon balm extract were also demonstrated.53 Inhibitory effects of rosmarinic acid from lemon balm on porcine pancreatic amylase were reported in vitro.54
  • Antiprotozoal effects: Essential oils, monoterpenes, and sesquiterpenes from lemon balm were tested on bloodstream forms of Leishmania major and Trypanosoma major. These constituents were reported to be about 50- to 80-fold more toxic to T major than were human HL-60 cells. None of the essential oils or terpenes were reported to be more toxic to L major than HL-60.33 Monoterpene and sesquiterpenes may possess antiprotozoal effects (anecdotal).
  • Antithrombotic effects: Rosmarinic acid has been reported to demonstrate inhibitory effects on both the classical pathway convertase and the alternative pathway convertase. One study reported that rosmarinic acid inhibited 70% of the immunohemolysis of antibody-coated sheep erythrocytes by guinea pig serum via possible inhibition of the C3 convertase of the classical complement pathway. However, higher concentrations of rosmarinic acid were less effective.28 Rosmarinic acid was also reported to inhibit C5 convertase in the classical pathway.48,28
  • Antithyroid effects: Studies have shown that freeze-dried extracts of lemon balm were reported to inhibit the binding of bovine TSH to human thyroid plasma membranes and adenylate cyclase. In rat liver microsomes, lemon balm aqueous extract was reported to inhibit the extrathyroidal enzymatic T4-5'-deiodination to both T3- and T4-5'-deiodination.16,15 The thyroid-stimulating immunoglobulin G (IgG) found in patients with Graves' disease has been reported to resemble TSH in its ability to bind to the thyroid plasma membrane and to activate the thyroid gland. Freeze-dried extracts of lemon balm were reported to exhibit antithyrotropic activity by forming adducts with TSH that bound weakly, if at all, to the TSH receptor. When IgG was incubated with extracts of lemon balm, a dose-dependent decrease was reported in the TSH-binding inhibitory activity. As a result of this reported decrease, adenylate cyclase activity was stimulated (thyroid-stimulating immunoglobulin activity) and thyroid iodine release was enhanced in the McKenzie assay system. Cinnamic acid has been reported to inhibit the binding of TSH to human thyroid membranes.15,16 In euthyroid rats, the administration of freeze-dried extracts of lemon balm was reported to reduce pituitary and serum TSH concentrations.17
  • Emmenagogic effects: One study suggested that freeze-dried extracts of lemon balm inhibited binding of 125I hCG to rat testis membranes.18 In rats, prolactin serum levels and hypophyseal stores were reported to be reduced by 40mg/100g of a freeze-dried extract of lemon balm.17
  • Spasmolytic effects: Due to lack of clinical data, lemon balm has not been recommended for use as a spasmolytic agent.9,10,11 Using histamine and acetylcholine as spasmogens in guinea pig ileum, no significant antispasmodic activity resulting from lemon balm extracts were reported.9 Studies on isolated duodenum of rat have reported antispasmodic effects of lemon balm in vitro.55
  • Sedative effects: In mice, an aqueous alcoholic extract of lemon balm was reported to produce dose-dependent sedation, inducing sleep and potentiating sub-hypnotic and hypnotic doses of pentobarbital. On the other hand, in the same study the essential oil of lemon balm was reported to have no sedative effect.7 With high doses, a peripheral analgesic effect was noted.7 In tests on Wistar strain rats and on laboratory mice, lemon balm dried extract was reported to exert influence on CNS in evoking antiaggressive activity. CNS studies of rat reported sedative, hypnotic, and analgesic effects of lemon balm in vivo.55 An ethanolic extract of lemon balm was tested for affinity to the GABA(A)-benzodiazepine site, and moderate activity was reported.56 However, a study of a volatile oil-free hydroalcoholic extract reported sedative activity in mice.
  • Cardiovascular effects: One study demonstrated that aqueous extracts of lemon balm provoked a significant reduction in the cardiac rate in isolated rat hearts, while the contractile force remained unchanged. This was reported to be caused by the stimulation of cardiac muscarinic receptors.57

Pharmacodynamics/Kinetics:

  • Insufficient available evidence.

References
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  2. Hohmann, J., Zupko, I., Redei, D., Csanyi, M., Falkay, G., Mathe, I., and Janicsak, G. Protective effects of the aerial parts of Salvia officinalis, Melissa Officinalis and Lavandula angustifolia and their constituents against enzyme-dependent and enzyme-independent lipid peroxidation. Planta Med 1999;65(6):576-578. 10532875
  3. Kucera, L. S. and Herrmann, E. C., Jr. Antiviral substances in plants of the mint family (labiatae). I. Tannin of Melissa officinalis. Proc Soc Exp Biol Med 1967;124(3):865-869. 4290277
  4. Lamaison, J. L., Petitjean-Freytet, C., and Carnat, A. [Medicinal Lamiaceae with antioxidant properties, a potential source of rosmarinic acid]. Pharm Acta Helv  1991;66(7):185-188. 1763093
  5. Triantaphyllou, K., Blekas, G., and Boskou, D. Antioxidative properties of water extracts obtained from herbs of the species Lamiaceae. Int J Food Sci Nutr 2001;52(4):313-317. 11474895
  6. Dragland, S., Senoo, H., Wake, K., Holte, K., and Blomhoff, R. Several culinary and medicinal herbs are important sources of dietary antioxidants. J Nutr  2003;133(5):1286-1290. 12730411
  7. Soulimani, R., Fleurentin, J., Mortier, F., Misslin, R., Derrieu, G., and Pelt, J. M. Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med 1991;57(2):105-109. 1891490
  8. Khayyal, M. T., el Ghazaly, M. A., Kenawy, S. A., Seif-el-Nasr, M., Mahran, L. G., Kafafi, Y. A., and Okpanyi, S. N. Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combination. Arzneimittelforschung 2001;51(7):545-553. 11505785
  9. Forster, H. B., Niklas, H., and Lutz, S. Antispasmodic effects of some medicinal plants. Planta Med 1980;40(4):309-319. 7220648
  10. Israel, D. and Youngkin, E. Q. Herbal therapies for perimenopausal and menopausal complaints. Pharmacotherapy 1997;17(5):970-984. 9324185
  11. Kennedy, D. O., Scholey, A. B., Tildesley, N. T., Perry, E. K., and Wesnes, K. A. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav  2002;72(4):953-964. 12062586
  12. Kucera, L. S., Cohen, R. A., and Herrmann, E. C., Jr. Antiviral activities of extracts of the lemon balm plant. Ann N.Y.Acad Sci 7-30-1965;130(1):474-482. 4285591
  13. May, G. and Willuhn, G. [Antiviral effect of aqueous plant extracts in tissue culture]. Arzneimittelforschung 1978;28(1):1-7. 204315
  14. Yamasaki, K., Nakano, M., Kawahata, T., Mori, H., Otake, T., Ueba, N., Oishi, I., Inami, R., Yamane, M., Nakamura, M., Murata, H., and Nakanishi, T. Anti-HIV-1 activity of herbs in Labiatae. Biol Pharm Bull 1998;21(8):829-833. 9743251
  15. Auf'mkolk, M., Ingbar, J. C., Kubota, K., Amir, S. M., and Ingbar, S. H. Extracts and auto-oxidized constituents of certain plants inhibit the receptor-binding and the biological activity of Graves' immunoglobulins. Endocrinology 1985;116(5):1687-1693. 2985357
  16. Auf'mkolk, M., Ingbar, J. C., Amir, S. M., Winterhoff, H., Sourgens, H., Hesch, R. D., and Ingbar, S. H. Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology 1984;115(2):527-534. 6745167
  17. Sourgens, H., Winterhoff, H., Gumbinger, H. G., and Kemper, F. H. Antihormonal effects of plant extracts. TSH- and prolactin-suppressing properties of Lithospermum officinale and other plants. Planta Med 1982;45(2):78-86. 7202226
  18. Auf'mkolk, M., Kohrle, J., Gumbinger, H., Winterhoff, H., and Hesch, R. D. Antihormonal effects of plant extracts: iodothyronine deiodinase of rat liver is inhibited by extracts and secondary metabolites of plants. Horm Metab Res 1984;16(4):188-192. 6724503
  19. Patora, J., Majda, T., Gora, J., and Klimek, B. Variability in the content and composition of essential oil from lemon balm (Melissa officinalis L.) cultivated in Poland. Acta Pol Pharm  2003;60(5):395-400. 15005424
  20. Mrlianova, M., Tekel'ova, D., Felklova, M., Reinohl, V., and Toth, J. The influence of the harvest cut height on the quality of the herbal drugs Melissae folium and Melissae herba. Planta Med 2002;68(2):178-180. 11859476
  21. Patora, J. and Klimek, B. Flavonoids from lemon balm (Melissa officinalis L., Lamiaceae). Acta Pol Pharm  2002;59(2):139-143. 12365606
  22. Ziakova, A., Brandsteterova, E., and Blahova, E. Matrix solid-phase dispersion for the liquid chromatographic determination of phenolic acids in Melissa officinalis. J Chromatogr A 1-3-2003;983(1-2):271-275. 12568390
  23. Araujo, C., Sousa, M. J., Ferreira, M. F., and Leao, C. Activity of essential oils from Mediterranean Lamiaceae species against food spoilage yeasts. J Food Prot  2003;66(4):625-632. 12696686
  24. Dimitrova, Z., Dimov, B., Manolova, N., Pancheva, S., Ilieva, D., and Shishkov, S. Antiherpes effect of Melissa officinalis L. extracts. Acta Microbiol Bulg  1993;29:65-72. 8390134
  25. Heitz, A., Carnat, A., Fraisse, D., Carnat, A. P., and Lamaison, J. L. Luteolin 3'-glucuronide, the major flavonoid from Melissa officinalis subsp. officinalis. Fitoterapia 2000;71(2):201-202. 10727822
  26. Agata I, Kusakabe H, Hatano T, and et al. Melitric acids A and B, new trimeric caffeic acid derivatives from Melissa officinalis. Chem Pharm Bull 1993;41(9):1608-1611.
  27. Tagashira M and Ohtake Y. New antioxidative 1,3-benzodioxole from Melissa officinalis. Planta Med 1988;64(6):555-558.
  28. Englberger, W., Hadding, U., Etschenberg, E., Graf, E., Leyck, S., Winkelmann, J., and Parnham, M. J. Rosmarinic acid: a new inhibitor of complement C3-convertase with anti- inflammatory activity. Int J Immunopharmacol  1988;10(6):729-737. 3198307
  29. Cohen RA, Kucera LS, and Herrmann EC. Antiviral activity of Melissa officinalis (lemon balm) extract (29600). Proceedings of the Society for Experimental Biology and Medicine 1964;117:431-434.
  30. Felklova, M., Natherova, L., and Duskova, K. [Tannin compounds in leaves of Melissa officinalis L., invaded by Septoria melissae Desm]. Cesk Farm  1969;18(9):457-460. 5370214
  31. Mulkens, A. and Kapetanidis, I. [Flavonoids of the leaves of Melissa officinalis L. (Lamiaceae)]. Pharm Acta Helv  1987;62(1):19-22. 3562477
  32. Thieme, H. and Kitze, C. [Occurrence of flavonoids in Melissa officinalis L]. Pharmazie 1973;28(1):69-70. 4714250
  33. Mikus, J., Harkenthal, M., Steverding, D., and Reichling, J. In vitro effect of essential oils and isolated mono- and sesquiterpenes on Leishmania major and Trypanosoma brucei. Planta Med 2000;66(4):366-368. 10865458
  34. Brieskorn, C. H. and Krause, W. [Further triterpenes from Melissa officinalis L (author's transl)]. Arch Pharm (Weinheim) 1974;307(8):603-612. 4848815
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  37. Mulkens, A and Kapetanidis, I. Eugenylglucoside, a new natural Phenylpropanoid Heteroside from Melissa officinalis. J Nat Prod 1988;51:496-498.
  38. Mulkens, A, Stephanou, E, and Kapetanidis, I. Heterosides a genines volatiles dans les feuilles de Melissa officinalis L. (Lamiaceae). Pharma Acta Helv 1985;60:276-278.
  39. Sarer, E and Kökdil, G. Constituents of the Essential Oil from Melissa officinalis. Planta Med 1991;57:89-90.
  40. Mulkens, A and Kapetanidis, I. Etude de l'huile essentielle de Melissa officinalis L. (Laminaceae). Pharm Acta Helv  1988;63:266-270.
  41. Carnat, AP, Carnat, A, Fraisse, D, and Lamaison, JL. The aromatic and polyphenolic composition of lemon balm (Melissa officinalis L, subsp officinalis) tea. 1998;72:301-305.
  42. Koch-Heitzmann, I and Czygan, FC. Über wasserdampfflüchtige Diterpenkohlenwasserstoffe in nicht differenzierten Oberflächenkulturen / Untersuchungen an Kalluskulturen von Melissa officinalis L. 1985;II(40c):13-20.
  43. Allahverdiyev, A., Duran, N., Ozguven, M., and Koltas, S. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2. Phytomedicine  2004;11(7-8):657-661. 15636181
  44. Larrondo, J. V., Agut, M., and Calvo-Torras, M. A. Antimicrobial activity of essences from labiates. Microbios 1995;82(332):171-172. 7630324
  45. Iauk, L., Lo Bue, A. M., Milazzo, I., Rapisarda, A., and Blandino, G. Antibacterial activity of medicinal plant extracts against periodontopathic bacteria. Phytother Res 2003;17(6):599-604. 12820224
  46. Friedman, M., Henika, P. R., Levin, C. E., and Mandrell, R. E. Antibacterial activities of plant essential oils and their components against Escherichia coli O157:H7 and Salmonella enterica in apple juice. J Agric Food Chem  9-22-2004;52(19):6042-6048. 15366861
  47. Mimica-Dukic, N., Bozin, B., Sokovic, M., and Simin, N. Antimicrobial and antioxidant activities of Melissa officinalis L. (Lamiaceae) essential oil. J Agric Food Chem  5-5-2004;52(9):2485-2489. 15113145
  48. Peake, P. W., Pussell, B. A., Martyn, P., Timmermans, V., and Charlesworth, J. A. The inhibitory 15113145 of rosmarinic acid on complement involves the C5 convertase. Int J Immunopharmacol  1991;13(7):853-857. 1761351
  49. Dimpfel, W., Pischel, I., and Lehnfeld, R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activity of volunteers. Eur J Med Res 9-29-2004;9(9):423-431. 15546807
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  51. Marongiu, B., Porcedda, S., Piras, A., Rosa, A., Deiana, M., and Dessi, M. A. Antioxidant activity of supercritical extract of Melissa officinalis subsp. officinalis and Melissa officinalis subsp. inodora. Phytother Res 2004;18(10):789-792. 15551397
  52. de Sousa, A. C., Alviano, D. S., Blank, A. F., Alves, P. B., Alviano, C. S., and Gattass, C. R. Melissa officinalis L. essential oil: antitumoral and antioxidant activities. J Pharm Pharmacol  2004;56(5):677-681. 15142347
  53. Drozd, J. and Anuszewska, E. The effect of the Melissa officinalis extract on immune response in mice. Acta Pol Pharm  2003;60(6):467-470. 15080594
  54. McCue, P. P. and Shetty, K. Inhibitory effects of rosmarinic acid extracts on porcine pancreatic amylase in vitro. Asia Pac J Clin Nutr  2004;13(1):101-106. 15003922
  55. Soulimani, R., Younos, C., Fleurentin, J., Mortiert, F., Misslin, R., and Derrieux, G. Recherche de l'Activit, biologique de Melissa officinalis L. sur le Systeme nerveux central de la souris in vivo et le Doudenum de Rat in vitro. Plant Med Phytother 1993;26:77-85.
  56. Salah, S. M. and Jager, A. K. Screening of traditionally used Lebanese herbs for neurological activities. J Ethnopharmacol  2-10-2005;97(1):145-149. 15652288
  57. Gazola, R., Machado, D., Ruggiero, C., Singi, G., and Macedo, Alexandre M. Lippia alba, Melissa officinalis and Cymbopogon citratus: effects of the aqueous extracts on the isolated hearts of rats. Pharmacol Res 2004;50(5):477-480. 15458767




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