Lemon Balm: What Is It Good For?

Lemon balm (Melissa officinalis L.), also known as drug grass or balm, is a perennial herbaceous plant in the family Lamiaceae that grows naturally in the Mediterranean region and is widely cultivated in Europe and North America. It is also found in the wild in central and southern China, Southwest China, and Taiwan Province, but is rarely cultivated[1]. The plant is about 50 cm tall, with umbels of white lip-shaped flowers. It flowers in July and August, and is named after the lemon-like fragrance of its stems and leaves[2].

In traditional Western herbal medicine, lemon balm is described as having the effect of delaying aging and preventing hair loss, and it also has health-promoting effects on the sick and weak. As a commonly used Western herb, lemon balm leaves, whole herb and extracted essential oil are all used as ingredients with therapeutic effects.

The fresh grass of lemon balm mainly contains polyphenols, ascorbic acid, carotene, flavonoids and terpene components, and the leaves are rich in flavonoids and other active substances that are beneficial to human health. Modern pharmacology shows that lemon balm has pharmacological effects such as anti-oxidation, anti-anxiety, anti-depression, improving menopausal symptoms in women, treating sleep disorders, improving cognition, heart health, treating obesity, and improving nighttime teeth grinding. The commonly used dosage forms mainly include dried plant leaves, dried leaf powder, extract tinctures, extract solutions, and capsules [3].

Due to the many health benefits of lemon balm, its use as a dietary supplement and functional food is also increasing. The dosage forms of lemon balm as a dietary supplement are mostly tincture extract, tea packaged in pieces for brewing, and capsules. In order to make better use of the areas in China with suitable growing conditions for Melissa officinalis and to develop this plant, which is widely used in the West, this article collects the scientific literature that can be found on Melissa officinalis. It reviews the chemical composition, pharmacological mechanism of action, and clinical research progress of Melissa officinalis in recent years at home and abroad, with the aim of promoting the use of Melissa officinalis in China.

1 Main chemical components of Melissa officinalis

The fresh plant of Melissa officinalis (L.) contains polyphenolic compounds, ascorbic acid, flavonoids and terpenoids. The polyphenolic compounds mainly contain rosmarinic acid, caffeic acid and protocatechuic acid. Among these, rosmarinic acid is the main component of Melissa officinalis L. ethanol extract, accounting for about 2% to 5% of the extract concentration, and caffeic acid accounts for about 0.1% of the total weight [4]. It is rich in essential oil (containing citral), and Chinese scholars have determined through research that the main component of essential oil is terpene substances, which mainly include: citral a (geranial), citral b (neral), caryophyllene oxide and caryophyllene. The content is also relatively high in squalene (Squalele). Squalene is a natural fat-soluble triterpene compound with strong oxygen-carrying capacity. It has biological activities such as anti-oxidation, anti-radiation, detoxification, and regulation of cholesterol metabolism [5,6].

Lemon balm extract contains flavonoids (0.5% of dry leaves), mainly including: quercitrin, ramnocitrin and luteolin and their derivatives (e.g. luteolin-7-O-glucoside, etc.) [7,8]. Other constituents include coumarins: 6,7-dihydroxycoumarin (aesculetin); glucosides (heterosides): β-glucosides with various aglycones; carbohydrates: stachyose; organic acids: succinic acid; vitamins: vitamin B1, vitamin B2, etc.; enzyme substances: peroxidase, etc. [9]. Experts in plant chemistry have isolated 1,3-benzodioxole, which has antioxidant properties, from lemon balm [10].

2 Health benefits of lemon balm

2.1 Central nervous system health benefits

2.1.1 Anti-depressant, anti-anxiety and sleep-promoting effects

The dried leaves of lemon balm are often used for their anxiolytic and antidepressant properties. They can reduce anxiety levels, help you sleep and have a calming effect. They can also prevent gastrointestinal motility caused by central nervous system disorders. It is generally recommended to drink a tea made from 2–3 g of dried leaves 3 times a day for its anxiolytic properties. In the forced swimming test in non-anxious mice, lemon balm was shown to have an antidepressant effect similar to that of imipramine (a tricyclic antidepressant) [11]. Other studies have shown that the antidepressant effect of lemon balm in the forced swimming test in mice is mainly produced by regulating the serotonin (5-HT) flip-flop in the brain and the mechanism associated with serotonin neurotransmission [12].

In rats, long-term administration of lemon balm (30 mg/kg, 100 mg/kg and 300 mg/kg of ethanol extract) was shown to have an anxiolytic effect, but a single dose of the same dose did not show a satisfactory anxiolytic effect [13]. Adding lemon balm to food can improve cognitive ability and a sense of well-being. Consumption of 0.3 g of lemon balm leaf extract (containing over 6% rosmarinic acid) can reduce anxiety and memory within 3 hours of consumption. Adding lemon balm leaf extract to yogurt can improve alertness, memory and calculation ability, but high doses can cause significant fatigue.

The above human experiments are not determined by a single neurotransmitter system, but may be caused by the interaction of multiple neurotransmitter systems. For example, lemon balm may extensively affect the nicotine-muscarinic receptor connection point, enhance alertness and strengthen memory. Lemon balm may have a regulatory effect on the cholinergic neurotransmitter system, As for the anxiolytic properties, it is possible that lemon balm's gamma-aminobutyric acid (GABA) can produce a regulatory effect on the nervous system, and the pharmacological mechanism of anxiolysis may be achieved by inhibiting the activity of GABA transaminase (GABA-T transaminase) to increase the concentration of GABA at the synapses [14].

A research team used Bioassay-guided Fractionation to measure the activity of lemon balm on GABA-T transaminase in vitro and proved that lemon balm has the effect of inhibiting the activity of GABA-T transaminase in vitro. The main active ingredients are rosmarinic acid, ursolic acid and oleanolic acid [15]. Lemon balm is often used in herbal medicine in Western countries as a sleep aid. Animal experiments on mice have shown that the intake of lemon balm extract (400 mg/kg and 800 mg/kg) can significantly reduce the time taken to fall asleep and increase the duration of sleep. The sleep-promoting effect of 800 mg/kg is similar to the sedative effect of the psychotropic drug diazepam; when taken together with lavender (Lavandula angustifolia) extract, it has a synergistic effect, significantly shortening the time to fall asleep and increasing the length of sleep, and can be used as an important treatment for insomnia [16].

2.1.2 Improving memory and neurodegenerative disease effects

Experiments have shown that lemon balm can effectively prevent memory impairment and neurodegenerative diseases. Lemon balm and its abundant rosmarinic acid can delay the degradation of acetylcholine through the inflammatory pathway, neuroprotective effect, and inhibition of acetylcholinesterase, increase the concentration of acetylcholine between nerve synapses, and delay the formation of β-amyloid protein, which can help relieve symptoms in patients with Alzheimer's disease [17]. Rats were injected intraperitoneally with 50–400 mg/kg of Melissa officinalis leaf extract, and some rats were also injected with scopolamine, which damages the nervous system.

A dose of 200 mg/kg of Melissa officinalis leaf extract significantly improved learning and memory in rats, reduced the pharmacological effects of scopolamine, and also inhibited acetylcholinesterase, increasing the concentration of acetylcholine at the synapses [18]. Melissa officinalis can reduce the gene expression of hypoxia-inducible factor 1α (HIF-1α). Melissa officinalis can be used as a neuroprotective factor to combat oxidative stress [19]. In a clinical trial, 20 patients with moderate to severe Alzheimer's disease were given 60 drops/day of Melissa officinalis leaf extract (1:1 volume 45% ethanol, containing 500 µg citral/mL) for 16 weeks. In parallel, 15 cases were given a placebo. Starting from the 8th week, lemon balm significantly improved the cognitive abilities of patients with moderate to severe Alzheimer's disease [20].

2.2 Antioxidant health effects

Lemon balm is rich in essential oils, which have strong antioxidant properties [21]. In vitro 1,1-diphenyl-2-trinitrobenzene hydrazone (DPPH) radical trapping showed that lemon balm's in vitro DPPH radical trapping capacity at 100–250 µg/mL was equivalent to the antioxidant effect of the control standard substance [22]. In addition to the in vitro DPPH radical trapping assay, Melissa officinalis has also been shown to have superoxide anion radical (O2 ·-) and nitric oxide radical (NO ·) trapping abilities. Melissa officinalis extract has also been found to have the ability to chelate divalent iron ions (Fe2+), which is also strong evidence of Melissa officinalis' antioxidant activity [23]. In a study, workers in the medical radiology department who were exposed to low concentrations of radioactive substances for long periods of time were given a lemon balm preparation (containing 1.5 g of dried lemon balm leaves) twice a day for 30 days. After taking the lemon balm, the concentration of the antioxidant enzymes superoxide dismutase and glutathione peroxidase in the workers' plasma increased significantly. and a reduction in DNA damage could also be detected. All of this indicates that lemon balm has a good anti-radiation effect [24].

2.3 Antibacterial and anti-inflammatory health effects

Lemon balm is rich in essential oils, which have a certain degree of antibacterial effect [25]. In vitro experiments have shown that it has a certain degree of antibacterial effect on Gram+ (Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes), some Gram- (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, and some fungi), Fusarium oxysporum, and Rammanella morganii [26].

In a rat foot swelling test, 200 mg/kg or 400 mg/kg of lemon balm essential oil was administered to rats by gavage, and the positive control group was given indomethacin (a non-steroidal anti-inflammatory drug) by gavage. It was found that both doses of lemon balm essential oil could relieve rat foot swelling [27]. Using an in vitro study of cyclooxygenase 2 (COX-2) protein expression in oral epidermoid carcinoma cells (KB cells), it was found that lemon balm water extracts at 50 µg/mL, 100 µg/mL and 500 µg/mL can reduce tissue-type plasminogen activator (TPA)-induced COX-2 protein expression, thereby producing an anti-inflammatory effect [28].

2.4 Other health benefits

2.4.1 Anti-cancer effects

In research, Melissa officinalis has also been found to have anti-cancer effects. In vitro experiments have found that Melissa officinalis ethanol extract has a significant inhibitory effect on estrogen receptor-positive MCF7 breast cancer cells, but no inhibitory effect on normal cells [29].

Lemon balm leaf extract at 5 µg/mL significantly inhibited the growth of human rectal cancer cells (HCT-116), and at a concentration of 1000 µg/mL significantly reduced HCT-116 cell viability [30].

2.4.2 Gastrointestinal health effects

A single administration of a methanol extract of lemon balm leaves (150 mg/kg, 300 mg/kg and 450 mg/kg) can protect rats against gastric ulcers. The possible pharmacological mechanism is to increase the activity of antioxidant enzymes and glutathione peroxidase and inhibit the phospholipid peroxidation of cell membranes [31].

2.4.3 Gynecological health effects

Lemon balm can also be used to treat menstrual disorders in women, such as irregular menstruation, dysmenorrhea and menorrhagia [32]. Lemon balm can reduce the systemic symptoms caused by dysmenorrhea. Fifty students with dysmenorrhea symptoms who took 330 mg of lemon balm leaf extract three times a day for three consecutive days significantly reduced the degree of exertion during dysmenorrhea [33].

2.4.4 Cardiovascular health effects

Lemon balm can support the treatment of hyperlipidemia. A rat study showed that different doses of lemon balm ethanol extract (25 mg/kg, 50 mg/kg and 75 mg/kg) given to hypercholesterolemic rats can reduce the activity of hepatic drug enzymes such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, and also lowers the blood cholesterol concentration, with an effect similar to that of atorvastatin, which is used to treat hyperlipidemia [34].

2.4.5 Weight loss and health maintenance effects

In a human trial with lemon balm, 20 cases were divided into two groups, which took green tea or lemon balm tea (2 × 2 g/day) for 2 months. Both groups of subjects experienced weight loss [35].

3 Research space

Lemon balm health food supplements are mainly used for central nervous system health, such as anti-anxiety and adjuvant treatment of insomnia, as well as antioxidant health effects. A review of the literature found that the various neurotransmitter systems in the central nervous system, including those related to antidepressants such as 5-HT, norepinephrine, and dopamine, could be studied in more detail to determine which neurotransmitter systems are affected by lemon balm to influence the operation of the central nervous system.

The active substances of Melissa officinalis were studied in depth, and more monomers were isolated and their chemical structures clarified. They were then synthesized using medicinal chemistry methods, and the pharmacological mechanisms were clarified using experimental animals to provide effective chemical monomers for antidepressant and anxiolytic drugs. For the antioxidant effect, the mechanism of action can be further clarified using the non-clinical system of experimental animals, in vivo studies can be strengthened, and changes in lipid oxidation products, protein oxidation products, antioxidant enzymes (SOD, etc.), and antioxidant substances (GSH, etc.) in animals can be analyzed to determine the pharmacological mechanism of antioxidants and other related research.

4 Conclusion

In summary, in recent years, European and American countries have conducted a lot of research on the health-promoting functions of Melissa officinalis, while there has been less research on this topic in China. These studies have shown that Melissa officinalis has a variety of health-promoting effects, including anti-depression, sleep-promoting effects on the central nervous system, a health-promoting effect on myocardial function, and an auxiliary effect on weight control. Western countries have used their advanced food processing industry to research and develop it, and lemon balm has been processed into dietary supplement capsules, substitute teas, and health tonics, which are widely recognized by consumers in Europe and the United States. Some dietary supplements use lemon balm as the main ingredient and add other herbs to create compound preparations, which better exert the synergistic health effects of various herbs.

In China, lemon balm is widely cultivated, but its use is still limited to gardening and its role as a medicinal herb (for the environment and air purification). Lemon balm is suitable for cultivation in the central, southern and southwestern regions of China. Due to the influence of the Internet, modern English education and economic globalization, some domestic consumers have begun to have a preliminary understanding of the health benefits of lemon balm, but this is limited to only some consumers.

With the improvement of living standards and health awareness in China, and the structural reform of the supply side promoted by the government, it is believed that the food processing industry can rely on the country's abundant planting resources to increase research and development of lemon balm in health foods, functional foods, and substitute teas, so that lemon balm can become industrialized in the field of health foods. In terms of popular science, publicity efforts should be increased on the health benefits of lemon balm, and it should be combined with the horticultural cultivation industry to develop synergistically and be used in a comprehensive manner to meet consumer demand for dietary health and disease prevention. Dietary supplements made from lemon balm have great development potential. If the horticultural industry can be combined with the development of lemon balm, and publicity efforts on the comprehensive use and health benefits of lemon balm can be increased, it will be of great practical significance for the healthy development of the domestic market.

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