What Are the Benefits of Lemon Balm Extract?

Melissa officinalis L, also known as lemon balm, is a perennial herb in the family Lamiaceae. The erect, much branched stem is pilose, becoming glabrous towards the base. The leaves are petiolate, with slender petioles, and have ovate-orbicular blades with crenate or obtuse serrate margins and nearly cordate bases. There are 4 pairs of lateral veins, reticulate veins are obvious on the upper surface, the midrib is nearly flat on the upper surface and raised on the lower surface. The umbels are axillary, with short pedicels, 2–14-flowered, and the bracts are small and leaflike. The calyx is campanulate, with a long spinose apex. Pedicel ca. 4 mm, villous. Corolla creamy white, 12–13 mm long, pilose. Upper lip straight, apex emarginate, lower lip 3-lobed. Flowering period: June–August.

Melissa officinalis is a robust plant that is extremely easy to cultivate and manage. Unlike other western medicinal herbs or aromatic plants introduced from temperate zones, it prefers moist soil and is cold, heat and water tolerant. It grows well in full sun or partial shade, has a wide range of soil adaptability, and is most suitable for a pH between 5 and 7.5. Melissa officinalis is quite adaptable to soil environments in various climates. It can be cultivated in fields, gardens and pots. Its stems and leaves are lush and dark green in color, and it has a strong fragrance.

Melissa officinalis originated in southern Europe and North America. It is mainly distributed in Mediterranean countries, including coastal areas of Turkey and northern Iran. It has also been cultivated in China. In the eleventh century, Arab herbalists believed that Melissa officinalis had the magical power to refresh the mind and soul. Melissa officinalis was often planted around churches or temples in ancient Europe, attracting bees to make honey for sacrificial purposes. Melissa officinalis is used for a variety of purposes, such as food additives, herbal teas, ingredients in cosmetics, decorations and medicines. When encountering insect bites or wounds, the fresh leaves of Melissa officinalis can be directly applied to the affected area to reduce swelling and pain; dried leaves can be made into medicinal pillows to help with sleep. It is currently widely used in medicine and pharmacology, with sedative, anti-anxiety, anti-tumor, antibacterial, anti-histamine, anti-oxidant, anti-ulcer, mood regulation and cognitive performance effects.

1 Lemon Balm Extract Active ingredients

1.1 Flavonoids

Lemon Balm Extract extract contains flavonoids including quercetin, rhamnetin, luteolin, etc. Free radicals are normal metabolic products in the body. When they are out of balance in the body, they may lead to many diseases such as inflammation, aging, cancer, and cardiovascular and cerebrovascular diseases. Flavonoids have a good scavenging effect on free radicals. Liu Shuang et al. [1, 2] and others have all experimentally demonstrated that quercetin, after being absorbed, indirectly or directly exerts an antioxidant effect in the body. It has been experimentally proven [3] that rhamnetin has a direct inhibitory effect on six tumor strains, including L1210, P388D1, HeLa, B16, NG108-15 and Hele7404. it was determined that luteolin has a certain in vitro antitumor effect. Wang Jishuang [4] and others believe that luteolin not only inhibits tumor cell proliferation, but also has a protective effect on the nervous system. In addition, luteolin also has anti-inflammatory and liver protection effects.

1.2 Polyphenolic compounds

Lemon Balm Extract extract is rich in various polyphenols such as rosmarinic acid, caffeic acid and protocatechuic acid. Zhou Dan [5] and others concluded that rosmarinic acid has a good therapeutic effect on tumors, inflammation, Alzheimer's disease and other diseases. Caffeic acid is a natural phenolic compound that is widely found in fruits and vegetables. It has a very high ability to remove DPPH and ABTS free radicals, and also has a strong reducing power for iron ions. Protocatechuic acid can reduce and improve the pathological damage to the brain tissue of Parkinson's disease model mice, exerting a neuroprotective effect by increasing the activity of endogenous antioxidant enzymes and reducing the production of free radicals [7].

1.3 Terpenoids

Lemon Balm Extract extract also contains monoterpenal, monoterpenoid, terpene, sesquiterpene and other compounds [8]. At present, the application of Melissa officinalis chemical composition mainly focuses on Melissa officinalis essential oil. Melissa officinalis essential oil can be obtained from various parts of Melissa officinalis by using different extraction methods. The six main components of Melissa officinalis essential oil are citronellal (14. 40%), isoeugenol (6. 40%), geranyl acetate (10. 20%), nerol (5. 10%), caryophyllene (8. 10%), and caryophyllene oxide (11 %), accounting for 55. 20% of the total essential oil [9].

2 Pharmacological effects

2.1 Anti-adipose tissue formation

Similar to tumor tissue, the growth and development of adipose tissue is considered to be angiogenesis-dependent. Melissa officinalis organic extract ALS-L1023 can inhibit the growth of adipose tissue blood vessels. Jeongjun Ki m [10] and others found that a high-fat diet (HF D) combined with ALS-L1023 without affecting caloric intake, C57BL/6J mice had reduced body weight, significantly lower abdominal blood glucose, lower serum ALT and AST levels, inhibited vascular growth in visceral adipose tissue, and improved lipid metabolism. ALS-L1023 also reduced the average size of visceral fat cells, inhibited fat degeneration, and significantly reduced fat in obese mice. In addition, ALS-L1023 also reduced the number of CD-68-positive macrophages and the expression level of inflammatory cytokines. This indicates that Melissa officinalis extract can play a therapeutic role in the occurrence and development of diseases such as obesity as a vascular growth inhibitor.

2.2 Sedative and anti-anxiety depression

Experimental studies have shown [11] that by establishing a mouse depression model [12-14], using sucrose water consumption experiments, open field experiments, and forced swimming experiments, it was found that after CUMS stimulation, the behavior of mice was assessed, and it was found that the essential oil and acetone water extracts of Melissa officinalis leaf both increased the number of spontaneous activities of mice and increased their interest in things. Mice given the petroleum ether extract were more active and more active. This indicates that Melissa officinalis extract has a definite antidepressant effect and a stronger antidepressant effect. GABA is an important inhibitory neurotransmitter in the central nervous system of mammals and is currently an important target for research on sedation, anti-anxiety and antidepressant effects.

Rosmarinic acid, one of the active ingredients in Melissa officinalis extract, has been shown in experiments [15] to inhibit GABA transaminase and inhibit the degradation of GABA, thereby increasing the concentration of GABA in the brain and having an anti-anxiety and sedative effect. In addition, two other main components of Melissa officinalis, caffeic acid and citral [16-18], have been shown in experiments to have anti-anxiety effects. In the forced swimming test, citral can significantly reduce the total immobility time of mice, and can reduce the total immobility time in synergy with imipramine. Some effective components of Melissa officinalis also have the effect of protecting neurons. They protect the nervous system by inhibiting the activity of cholinesterase in the synaptic cleft [19] and increasing the activity and content of ACh. Melissa officinalis extract can protect against methylene-dioxy-methamphetamine-induced apoptosis of hippocampal primary neuronal cells, through its strong antioxidant properties and inhibition of MAO. Melissa officinalis can therefore be used as an antidepressant and neuroprotective agent to relieve stress, improve psychological mood, regulate cognitive performance, and prevent neurodegenerative diseases [20].

2.3 Antitumor

Alviano DS [21] and others used the MTT method to conduct an in vitro cytotoxicity test and found that Melissa officinalis extract has a good inhibitory effect on a series of human cancer cell lines (A549, MCF-7, Caco-2 cells, HL-60, K562) and mouse cell lines (B16F10) have a good inhibitory effect, indicating the potential use of Melissa officinalis as a tumor suppressor. Jahanban-Esfahlan A [22] and others used the MTT method to detect the cytotoxic effect of the extract and conducted selective anti-cancer experiments on Melissa officinalis extracts in different human cancer cells.

The results showed that even at the lowest dose (5–1000 μg·mL-1), Melissa officinalis extract reduced the survival rate of all cancer cells to below 33%. It was also found that the average tumor inhibition rates of SKOV3, MCF-7, PC-3, A549 4 kinds of cells, the average tumor inhibition rate reached 73.1%, 86.7%, 79.9%, 77.8% respectively. The experimental results show that Melissa officinalis water extract has a high inhibitory effect on tumor cell proliferation, regardless of its dose size. This indicates that the optimal biological dose of Melissa officinalis as a tumor inhibitor is more important than the maximum tolerated dose. In addition, hormone-dependent cancers are more sensitive to Melissa extracts, suggesting that Melissa has specificity in antitumor activity.

2.4 Antioxidant properties

Medicinal plants rich in polyphenolic compounds are widely used for their good antioxidant properties. Safaeian L[ 23] and others found that H2O2-induced human venous endothelial cells treated with Melissa officinalis extract can significantly improve cell viability, reduce the concentration of peroxides, and improve the antioxidant capacity of intracellular and extracellular fluids.

Rosmarinic acid, the main active ingredient in Melissa officinalis extract, is an antioxidant. Experiments have shown that [24] giving medium to high doses of rosmarinic acid can significantly reduce malondialdehyde levels and serum triglyceride levels, thereby increasing the activity of antioxidant enzymes in the body, and that there is a dose-response relationship with increasing doses of rosmarinic acid. Under hypoxic conditions, the body experiences an imbalance in free radical metabolism, enhanced lipid peroxidation, and a decrease in antioxidant capacity. The results of the experiment showed that medium and high doses of rosmarinic acid can increase the time that aging mice can withstand hypoxia under normal pressure.

The mechanism of action may be that rosmarinic acid reduces the body's oxygen consumption, and the production of oxygen free radicals is subsequently reduced. The stronger the body's antioxidant capacity, the more effective it is in achieving the therapeutic goal of anti-aging [25].

Rosmarinic acid also has anti-angiogenic activity, can reduce the expression of H2O2-dependent vascular endothelial growth factor, and can inhibit endothelial cell oxidation of low-density lipoprotein [26], reduce the release of IL-8 from endothelial cells, and inhibit the proliferation, migration, and adhesion of endothelial cells [27]. In addition, caffeic acid, another antioxidant in Melissa officinalis extract [28], may improve cellular resistance to oxidative stress by inhibiting lipid peroxidation and reducing glutathione depletion [29]. Due to its strong antioxidant activity, Melissa officinalis extract has potential benefits for the prevention of cardiovascular diseases associated with oxidative stress.

2.5 Antibacterial

Natural essential oils are obtained from various parts of plants and are highly effective active antibacterial agents. The widespread use of antibacterial drugs has seriously affected the effectiveness of antibiotic treatment. The use of herbs is a preventive measure against treatment failures due to a lack of sensitivity to synthetic antibiotics. Experiments have shown that the compounds in Melissa officinalis essential oil that exert an antibacterial effect are citral, citronellal and trans-caryophyllene. Melissa officinalis essential oil exhibits a high degree of antibacterial activity against Gram-positive bacteria and is also highly active against Candida albicans. Canadanovi et al. found that Melissa officinalis n-butanol extract had high lipid peroxide scavenging activity and hydroxyl radical scavenging activity. Melissa officinalis petroleum ether and ethyl acetate extracts have good antibacterial activity against Streptococcus mutans, and chloroform extracts have antiproliferative effects on He La cells and MCF-7 cells. This indicates that Melissa officinalis extracts have high phenolic content and free radical scavenging capacity, antibacterial activity and antiproliferative activity.

2.6 Anti-ulcer

Saber i A[30] et al. established a rat gastric ulcer model and found that Melissa officinalis formaldehyde extract can significantly reduce the ulcer index and the MDA level in rat serum. The mechanism by which Melissa officinalis formaldehyde extract protects the gastric mucosa may be through regulating the expression levels of the antioxidant enzymes SOD and GPX, or by reducing the MDA level, which are biochemical indicators that affect cell damage and lipid peroxidation. In addition, the natural antioxidant ingredients in Melissa officinalis formaldehyde extract, such as vitamin E, rosmarinic acid, and flavonoids, can also reduce the total amount and acidity of gastric acid and increase the pH of gastric juice. This indicates that Melissa officinalis extract may achieve an anti-ulcer therapeutic effect by mediating antioxidant properties.

3 Conclusion

Melissa officinalis is a folk herb with a wide range of applications, which proves its high medicinal value. In recent years, Melissa officinalis essential oil has shown unique advantages in clinical antitumor, antioxidant and antibacterial activities, which fully highlights the therapeutic characteristics of traditional Chinese medicine. However, at present, there is a lack of research on the links and mechanisms of action related to the chemical composition and clinical treatment of Melissa officinalis, so research and discussion on the chemical composition and pharmacological research of Melissa officinalis should continue to provide a scientific basis for better exploring the medicinal prospects of Melissa officinalis.

References

[1]Liu Rui, Meng Fang, Bai Huai. Research on the inhibitory effect of quercetin, rutin and puerarin on the oxidative modification of LDL [J]. Chinese Journal of Traditional Chinese Medicine, 2007, 32 (19): 2085-2062.

[2]Zhao Liting, Guo Changjiang, Cai Donglian, et al. Effects of quercetin supplementation on the antioxidant system of rat peripheral blood [J]. Journal of the Armed Police Medical College, 2009, 18 (4): 269-279.

[3]Sun Juan, Yu Shichun. Research progress of quercetin [J]. Modern Chinese Medicine Research and Practice, 2011, 25(3): 85- 87.

[4]Wang J S, He Y, Hua Z C, et al. Research progress on the pharmacological effects of luteolin [J]. Life Sciences, 2013, 25(6): 561- 564.

[5]Zhou D, Liu A, Du G. Pharmacological research progress of rosmarinic acid [J]. Chinese Journal of New Drugs, 2011, 20(7): 594-597.

[6]Fan J, Cai X, Feng X, et al. Study on the in vitro antioxidant activity of caffeic acid [J]. Chinese Journal of Food Science, 2015, 15(3): 66- 71.

[7]Zhang Xiuli, Li Yachen, Niu Xinhua, et al. Effects of protocatechuic acid on the antioxidant capacity of brain tissue in Parkinson's disease model mice [J]. Advances in Modern Biomedicine, 2011, 17(12): 3249- 3251.

[8]Sofowor a  A，Ogunbodede   E，Onayade  A. The  role  and  place  of  medicinal plants  in  the  strategies  for disease prevention[J］. Afr J Tradit Complement Alter n Med. ，2013，（10）: 210- 229.

[9]Gurck L，DubravskaR，Mikl ovicova. Economics of the cultivation of  Sal   officinalis    and   Melissa   officinalis[J］. Agric. Econ. Czech. ， 2005，51: 348- 356.

[10] Jeongi un  kim，Haerim Lee，Jonghoon  Lim. The  Angiogenesis  Inhibit or    ALS- L1023    from  Lemon- Balm  Leaves    Attenuates High- Fat Diet- Induced Nonalcoholic Fatty Liver Disease through Regulating the  isceral Adipose- Tissue Fu- nction[J］. Internation al Journal of Molecular Sciences，2017，18（4）:864.

[11] Ji Ziyang. Research on the chemical composition and antidepressant effect of Melissa officinalis [D]. Xinxiang: Xinxiang Medical College, 2016.

[12]Petit- Demouli er e B，Chenu F，Bouri n M.Forced swimming test  in  mice:  a reviewof antidepressant activity[J］. Psychopharmacology，2005，177（3）: 245- 255.

[13]Slattery DA，Cryan J F. Using the rat forced swimtest to assess an-  ti depressant- like activity in rodents[J］. Nature protocols，2012，7（6）:  1009- 1014.

[14]Sun Shiguang, Liu Jian, Lu Yan, et al. Correlation between the forced swimming test and tail suspension test for depression in Kunming mice [J]. Chinese Journal of Pharmacology and Toxicology, 2014, 28 (1): 107-111.

[15]Weitzel C，Petersen Met et al. Cloning and characterisation of ros-  marinic acid synthase fromMelissa officinalis L[J］. Phytochemistry， 201l，72（7）:  572- 578．

[16] Kennedy  DO，Little  W，Haskell  CF et  al. Anxi ol ytic  effect s  of  a combination of Melissa officinalis and Valeri ana officinalis during laboratory induced stress[J］. Phytother Res. ，2006，20（2）: 96- 102.

[17]David O. Kennedy，Wendy Little，Crystal F Haskell and AndrewB.  Scholey Anxi ol ytic Effect s of a Combination of Melissa officinalis and Valeri ana  officinalis  during Laboratory  induced Stress[J］.  Phytotherapy Research，2006，8（20）: 96- 102.

[18] Soodi   M，Naghdi  N，Hajimehdi poor   H，et   al. Memory- improving activity of Melissa officinalis extract in nave and scopolamine-   treated rats[J］. Research in pharmaceutical sciences，2014，9（2）: 107.

[19]Taher pour A，Maroof i H，Rafi e Z，et al. Chemical composition anal-   ysi s of t he essential oil ofMelissa officinalis L. fromKurdistan，Iran by HS/SPME method and calculation of the biophysicochemical   coefficient s of t he components[J］. Natural product research，2012， 26（2）: 152- 160.

[20]Lin S H，Chou  ML，Che n  WC，et al. Amedicinal  herb，Melissa officinalis  L. ameliorates  depressive- like  behavior  of  rats  in  the forced swimming test via regulating. the  serotonergic neurotrans-  mitter[J］. Journal of Ethnopharmacology，2015，175: 266- 272.

[21] de  Sousa  AC1，Alviano  DS，Blank  AF，Gatt ass  CR，et  al. Melissa officinalis L. essential oil：anti tumoral and antioxidant activities[J］. J. PharmPharmacol，2004，56（5）: 677- 81.[22] Jahanban- Esfahlan  A，Modaeinama   S，Jahanban- Esfahlan  R，et al. Anti Proliferat ive Properties of Melissa officinalis  in Different Human  Cancer  Cell s   [J］. Asian  Pac  J  Cancer  Prev. ，2015，16 （14）: 5703- 7.

[23]Leil a Safaeian，Seyyed Ebr ahimSajj adi，Fariba Samani，et al. Protecti ve effect  of Melissa officinalis  extract  against  H2O2- induced  oxidative stress in human vascular endotheli al cells[J］. Res Pharm Sci. ，2016，11（5）:  383- 389.

[24]Wang Hong, Liu Min, Gu Jianxiang, et al. Study on the antioxidant effect of rosmarinic acid on D-galactose-induced aging mice [J]. Chinese Journal of Gerontology, 2009, (5): 549-551.

[25]Zhang Hongquan, Yu Wenxin. Chinese anti-aging medicine [M]. Beijing: Science Press, 2000. 94-103.

[26]Pearson DA，Frankel EN，Aeschbach R，German JB.  Inhibition of  endotheli al cell- mediated oxidation of low- density lipoprotein by rosemary and plant  phenolics[J］. J. Agric. Food Chem.，1997，45： 578- 582.

[27]Huang SS，Zheng RL. Rosmarinic acid inhibit s angiogenesis and its mechanismof action in vitro[J］. Cancer Let t. 2006；239: 271- 280.

[28]Li PG，Xu  J W，Ikeda K，Kobayakawa A，Kayano Y，Mitani T，et al. Caffeic acid inhibits vascular smooth muscle cell proliferation induced by angiotensin II in strokeprone spontaneously hypertensive rats[J］. Hyper tens Res. ，2005，28: 369- 377.

[29]Nardini MPisu P，Gentil i V，Natell a F，Di  Felice M，Piccol ella E， et  al. Effect  of caffeic  acid on tert- but yl  hydroperoxide- induced  oxidative  stress  in  U937[J］. Free  Radic  Biol . Med. ，1998，25： 1098- 1105.

[30]Saber i  A，Abbas loo E，Sepehri  G，Yazdanpanah  M，Mir kamandari  E，Sheibani V，Safi Z. The Effects of Methanol ic Extract of Melissa officinalis  on Experimental Gastric Ulcers in Rats[J］. Iran Red  Crescent Med. J. ，2016，18（7）: e24271.