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Abstract

It is seen that the anxiety disorders are one of the most recurrent mental disorders in this world and contributes significantly towards the distortion of the quality of life of an individual. The traditional pharmacological drugs though effective are associated with several side effects such as sedation, dependence and tolerance when used long-term. This has increased the interest in the utilization of low risk and acceptable usage of herbal medicines. “Melissa officinalis L., one of the most frequent medicinal plants and also known as lemon balm, belongs to the family of Lamiaceae that has traditionally been used in the management of anxiety, stress, insomnia and nervous disorders treatment. It has numerous bioactive phytoconstituents including rosmarinic acid, flavonoid, phenolic, and essential oils that are essential in anxiolytic, sedative, antioxidant and neuroprotective actions. Functional foods are a new drug delivery mechanism which has been popular during the past years. The herbal extracts would be very well-captured by chocolate since it is palatable and mood-altering. Melissa officinalis extract added to herbal chocolate may be beneficial to the therapeutic compliance and acceptance of patients. This review languishes on the botanical description, phytochemical components, pharmacology, and the mode of its extraction and the potential application of the Melissa officinalis in the production of herbal chocolate to control anxiety.

Keywords

Anxiety, Melissa officinalis, Lemon balm, Herbal chocolate, Anxiolytic activity Functional food, Phytochemistry

Introduction

Anxiety is a normal expression of emotion to stress but under all circumstances when they are too many, too protracted, and uncontrollable; they lead to anxiety disorders. The anxiety disorders are among the most prevalent mental illness in the world and a major problem to the public health. Among the symptoms of these disorders are too much fear, worry, nervousness, restlessness, irritability, emotional instability etc. It may impact greatly adversely the operation of the everyday existence, educational performance, work performance and interpersonal connections in case the anxious reports stretch out over a prolonged interval. Benzodiazepines, antidepressants, and other entities that result in anxiology would be included in the key pharmacological treatment of anxiety. Although said drugs are useful in reducing anxiety symptoms, it has many limitations like it sedates, impairs the human mind, becomes tolerant, dependence, and withdrawal symptoms in the prolonged use of the drug. These adverse effects have led to the growing need to seek to have an alternative type of therapeutic modalities, which are safer and less toxic. The growing popularity of herbal medicines has been due to their natural origin, and long traditional usage as well as comparatively less side processes. Among such medicinal plant is Melissa officinalis L. or lemon balm which is also referred to as Melissis. Traditionally, it has been used over the centuries across various systems of medicine, where it was used to treat the anxiety, stress, insomnia, nervous conditions, and the cognitive abilities. It has been suggested as anxiousogenic and tranquilizer agent which may be a prolific herbal medication with anxiogene effect.

PLANT PROFILE:

Melissa officinalis, also known as lemon balm, melissa or sweet balsam, a perennial plant that has a lemon-like smell. Family- Laminaceae (Awad, et al; 2009). It produces heights up to 30-125 cm in height with short hairs or make up 4-12 small inflorescences producing in the summer months. The total stamen count is 2 and the number of lobed ovaries is 4 that constitute 1-4 nuts. Seeds 1-1.5mm long Ovate seeds are brown and black. Lemon balm grows rapidly in a temperature of 35 o C, a rainfall of between 500 to 600mm and propagates sporadically in the proliferation phase”. The irrigation is requisite (Saeb, et al; 2012). Melissa officinalis is a plant with haired root system that has many lateral roots thereby adapting it a lot to the different external environmental factors.

Table: Taxonomical Classifications of Melissa oficinalis

The concept of drug delivery using the functional foods is a new concept that has been realized over the recent years. Chocolate is one of the food products which got a considerable application because of the good taste and the ability to make the mood higher. It is abundant in bioactive, such as flavonoids or serotonin-modifying materials, and this has a beneficial impact on the psychological state. Vitamin, Adding Melissa officinalis extract into chocolate can be beneficial in providing a new convenient patient-friendly dosage. Therefore, this review aims at providing a general discussion on Melissa officinalis, the phytochemical and pharmacological features of this plant, the method of extract, and how this plant can be used in herbal chocolate as a remedy to anxiety.

Botanical Description of Meliss aofficinalis: -

Melissa officinalis L. is an of family Lamiaceae which is perennial and aromatic. It can also be referred to as lemon balm due to the fact that it contains active volatile essential oils that give a lemon aroma to the leaves.

  • Scientific name: Melissofficinalis L.
  • Family: Lamiaceae
  • Common name: Lemon balm
  • Plant part used: Leaves

Geographical distribution: native to Europe and the Mediterranean area where it is commonly cultivated in the temperate regions of Asia and the Middle East among others.

This plant grows up to a height of 70-150 cm and thereafter possesses serrated and ovate leaves with a distinct smell. The primary organ that is utilized as medication is the leaves that are extensively used as herbal extract. Melissa officinalis is rather significant to traditional and contemporary herbal medicine wherein its therapeutic variety is relatively high, in addition to presenting a beautiful fragrance.

Phytochemical Constituents: -

It is attributed to its pharmacological activity that is associated with its different phytochemical compositions. The plant contains numerous bioactive compounds that are mainly phenolic acids, flavonoids, essential oils and terpenes.

Major phytochemical constituents include:

Rosmarinic acids Caffeic acid Flavonoid: luteolin, quercetin, apigenin Phenolic compounds Volatile essential oils: citral, citronellal, geraniol and linalool Tannin and terpenes

Rosmarinic acid of them will be considered as the most significant substance, which leads to the anxiogenic and antioxidant effect of the plant. This synergistic action of these phytochemicals has contributed to the tranquilizing, relaxing, anti-oxidant, and neuroprotective property of Melissa officinalis.

Pharmacological Activities of Melissa officinalis:

Anxiolytic Activity

The literature conducted up to date has demonstrated that Melissa officinalis possess anxiolytic properties and this has been confirmed by countless experimental and clinical research. The mediation of the anxiolytic activity is carried out mainly by the central nervous system. It is claimed that the plant builds up the activity of gamma-aminobutyric acid (GABA) by inhibiting GABA transaminase and thus increasing the level of GABA in the brain. The overall result of this is the reduction of neuron excitability and discouraging effect.

Sedative and Antidepressant Activity:

A little sedative and antidepressant can also be obtained using Melissa officinalis. The advantages are that the effects are used in medication of such illnesses as insomnia, nervous tension, and mood disturbances. The plant also promotes sleepiness and it does not leave a person too drowsy as it is with synthetic drugs and it enhances the quality of sleep without the occurrence of addiction.

Antioxidant:

Melissa officinalis contains a great level of phenol which is a potent antioxidant. In the development of the anxiety and other neuropsychiatry disorders, oxidative stress is highly contributive. The oxidative damage is minimized and the plant helps in the defense of the nerve cells as such contributing to the brain as a whole.

Pharmacological Effects:

  • Antidepressants
  • Anxiolytic (Anti-anxiety)
  • Cytotoxic
  • Antioxidant
  • Neuroprotective
  • Antidiabetic
  • Antimicrobial

Extraction Method of Melissa officinalis: -

Extraction of bioactive compounds from Melissa officinalis is an important step in the preparation of effective herbal formulations. Various conventional and advanced extraction techniques are employed.

Solubility Test:

0.5 grams of casein to 2 milliliters of 0.1 N NaOH, 2 milliliters of 0.1 N HCL, and 2 milliliters of distilled water separately to test the solubility of the protein. After soaking the tubes in water for ten minutes, remove them; casein dissolves entirely in 0.1N NaoH.

Preparation of sample solution

Break Down 100 ml of 0.1N NaoH with 1g of casein added to make a solution.

Biuret test

Add 2 ml of 10% NaoH solution, 3–4 drops of 1% copper sulfate solution and mix with 2 ml of protein solution. When a peptide bond is present and the solution under analysis is a protein, purple is produced.

Test for Alkaloids

Using 5 mL of 1% HCL, each extract (0.5 g) was agitated in a steam bath. The resultant solution was filtered, and a few drops of Mayer’s reagent were added to one milliliter of the filtrate. The presence of alkaloids in the extract was determined by the turbidity of the filtrate after adding Mayer’s reagent.

Test for Glycosides

One milliliter of pyridine and a few drops of sodium nitropruside solution were added to the hydrolysate, and sodium hydroxide solution was then added to make it alkaline. A pink to red appearance indicates the prese

Common extraction methods include:

Soxhlet extraction, Maceration, Hydro-alcoholic extraction using ethanol and water, Ultrasound assisted extraction, Hydro-alcoholic solvents are widely preferred due to their efficiency in extracting phenolic compounds and flavonoids. The selection of extraction method significantly affects the yield, quality, and therapeutic efficacy of the extract.

Herbal Chocolate as a Novel Drug Delivery System:

Chocolate is a highly tolerable functional food and has become attracted as a new way of delivering drugs. It is a good carrier, as it is palatable, the tolerability of a broad group of consumers is large, and it can compensate for the bad flavor of herbal extracts. It also contains chocolate flavonoids and compounds that raise the level of serotonin, which would help in raising the mood. Melissa officinalis extract incorporation into chocolate should be enhanced with more compliance to patients because of the presence of anxiety active synergies. The strength with herbal chocolate is related to administration in an uninvolved, non-invasive, and patient-compliant dosage mode, especially to patients who dislike natural treatments over conventional drugs-based therapy.

Future Perspectives:

The management of anxiety practice can use an innovative and prospective method of using herbal chocolates using anxiogenic/anxiolytic plant extracts. However, further experimental studies and clinical trials will be required which will provide the stability of formulation, efficacy, safety, and effect in the long term. The production and commercialization of herbal extracts in large proportions also needs standards and quality controls of herbal extracts.

CONCLUSION

Melissa officinalis is a desirable medicinal plant and has been highly documented that it possesses anxiolytic, sedative, antioxidant and neuro protective properties. It is rich in phytochemicals, hence the reason why it can be used in treating, anxiety and other related disorders in the traditional setting. Addition of the Melissa officinalis extract into herbal chocolate offers a fresh and less toxic to patients’ dosage of Melissa officinalis that can either promote treatment adherence and efficacy. This system of therapy is enormous, as the alternative or supplementary way of addressing anxiety.

Flow Diagram

REFERENCES

  1. World Health Organization Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: WHO; 2017.
  2. Baldwin D.S., Stein D.J., Dolberg O.T., Gergel I. How long should a trial of pharmacotherapy for anxiety disorders last? CNS Spectrums. 2007;12(8):21–30.
  3. Sarris J., Panossian A., Schweitzer I., Stough C., Scholey A.Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. European Neuropsychopharmacology. 2011;21(12):841–860.
  4. Kennedy D.O., Scholey A.B.The psychopharmacology of European herbs with cognition- enhancing properties. Current Pharmaceutical Design. 2006;12(35):4613–4623.
  5. Shakeri A., Sahebkar A., Javadi B.Melissa officinalis L. – A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology. 2016;188:204–228.
  6. Cases J., Ibarra A., Feuillère N., Roller M., Sukkar S.G. Pilot trial of Melissa officinalis L. leaf extract in the treatment of anxiety disorders. Mediterranean Journal of Nutrition and Metabolism. 2011;4(3):211–218.
  7. Hosseinzadeh H., Nassiri-Asl M Pharmacological effects of Melissa officinalis L. Iranian Journal of Basic Medical Sciences. 2014;17(3):189–196.
  8. Awad R., Muhammad A., Durst T., Trudeau V., Arnason J.T. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.). Phytotherapy Research. 2009;23(8):1075–1081.
  9. Miraj S., Rafieian-Kopaei M., Kiani S. Melissa officinalis L.: A review study with antioxidant perspective. Journal of Evidence-Based Complementary & Alternative Medicine. 2017;22(3):385– 394.
  10. European Medicines Agency (EMA). Assessment report on Melissa officinalis L., folium. EMA Herbal Medicinal Products Committee; 2013. Carnat A.P., Carnat A., Fraisse D., Lamaison J.L. The aromatic and polyphenolic composition of lemon balm. Fitoterapia. 1998;69(2):159–164.
  11. Sadraei H., Ghannadi A., Malekshahi K. Relaxant effect of essential oil of Melissa officinalis. Phytotherapy Research. 2003;17(7):733–736.
  12. Yarnell E., Abascal K. Lemon balm (Melissa officinalis). Alternative and Complementary Therapies. 2006;12(3):131–133.
  13. Ulbricht C., Brendler T., Gruenwald J. Lemon balm (Melissa officinalis L.): An evidence-based systematic review. Journal of Herbal Pharmacotherapy. 2005;5(4):71–114.
  14. Shakeri A., Sahebkar A., Javadi B. Traditional and modern uses of Melissa officinalis in neurological disorders. Avicenna Journal of Phytomedicine. 2016;6(4):336–348.
  15. Patora J., Klimek B. Flavonoids from lemon balm (Melissa officinalis L.). Acta Poloniae Pharmaceutica. 2002;59(2):139–144.
  16. Dastmalchi K., Dorman H.J.D., Oinonen P.P., Darwis Y., Laakso I., Hiltunen R. Chemical composition and antioxidant activity of Melissa officinalis extract. LWT – Food Science and Technology. 2008;41(3):391–400.
  17. Scholey A., Kennedy D. Cognitive and mood effects of herbal extracts. Current Topics in Nutraceutical Research. 2004;2(1):13–24.
  18. Barros L., Carvalho A.M., Ferreira I.C.F.R. Leaves, flowers, immature fruits and leafy stems of lemon balm: Nutritional value and antioxidant activity. Food Chemistry. 2010;123(2):388–393.
  19. Perry N.S., Houghton P.J., Sampson J., Theobald A., Hart S., Lis-Balchin M., Hoult J.R.S., Evans P., Jenner P., Milligan S., Perry E.K.
  20. In vitro activity of Melissa officinalis against acetylcholinesterase and its potential use in neurological disorders. Journal of Pharmacy and Pharmacology. 2001;53(10):1347–1356.
  21. Asadi-Samani M, Bahmani M, Rafieian-Kopaei M. Herbal medicine for anxiety: A systematic review. J Evid Based Integr Med. 2016;21(4):242–253.
  22. Shakeri A, Sahebkar A, Javadi B. Melissa officinalis L.—A review of traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2016;188:204–228
  23. Saeb, K. & Gholamrezaee, S. (2012). Variation of essential oil composition of Melissa officinalis L. leaves during different stages of plant growth. Asian Pacific Journal of Tropical Biomedicine, 2(2): 347-349.

Reference

  1. World Health Organization Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: WHO; 2017.
  2. Baldwin D.S., Stein D.J., Dolberg O.T., Gergel I. How long should a trial of pharmacotherapy for anxiety disorders last? CNS Spectrums. 2007;12(8):21–30.
  3. Sarris J., Panossian A., Schweitzer I., Stough C., Scholey A.Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. European Neuropsychopharmacology. 2011;21(12):841–860.
  4. Kennedy D.O., Scholey A.B.The psychopharmacology of European herbs with cognition- enhancing properties. Current Pharmaceutical Design. 2006;12(35):4613–4623.
  5. Shakeri A., Sahebkar A., Javadi B.Melissa officinalis L. – A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology. 2016;188:204–228.
  6. Cases J., Ibarra A., Feuillère N., Roller M., Sukkar S.G. Pilot trial of Melissa officinalis L. leaf extract in the treatment of anxiety disorders. Mediterranean Journal of Nutrition and Metabolism. 2011;4(3):211–218.
  7. Hosseinzadeh H., Nassiri-Asl M Pharmacological effects of Melissa officinalis L. Iranian Journal of Basic Medical Sciences. 2014;17(3):189–196.
  8. Awad R., Muhammad A., Durst T., Trudeau V., Arnason J.T. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.). Phytotherapy Research. 2009;23(8):1075–1081.
  9. Miraj S., Rafieian-Kopaei M., Kiani S. Melissa officinalis L.: A review study with antioxidant perspective. Journal of Evidence-Based Complementary & Alternative Medicine. 2017;22(3):385– 394.
  10. European Medicines Agency (EMA). Assessment report on Melissa officinalis L., folium. EMA Herbal Medicinal Products Committee; 2013. Carnat A.P., Carnat A., Fraisse D., Lamaison J.L. The aromatic and polyphenolic composition of lemon balm. Fitoterapia. 1998;69(2):159–164.
  11. Sadraei H., Ghannadi A., Malekshahi K. Relaxant effect of essential oil of Melissa officinalis. Phytotherapy Research. 2003;17(7):733–736.
  12. Yarnell E., Abascal K. Lemon balm (Melissa officinalis). Alternative and Complementary Therapies. 2006;12(3):131–133.
  13. Ulbricht C., Brendler T., Gruenwald J. Lemon balm (Melissa officinalis L.): An evidence-based systematic review. Journal of Herbal Pharmacotherapy. 2005;5(4):71–114.
  14. Shakeri A., Sahebkar A., Javadi B. Traditional and modern uses of Melissa officinalis in neurological disorders. Avicenna Journal of Phytomedicine. 2016;6(4):336–348.
  15. Patora J., Klimek B. Flavonoids from lemon balm (Melissa officinalis L.). Acta Poloniae Pharmaceutica. 2002;59(2):139–144.
  16. Dastmalchi K., Dorman H.J.D., Oinonen P.P., Darwis Y., Laakso I., Hiltunen R. Chemical composition and antioxidant activity of Melissa officinalis extract. LWT – Food Science and Technology. 2008;41(3):391–400.
  17. Scholey A., Kennedy D. Cognitive and mood effects of herbal extracts. Current Topics in Nutraceutical Research. 2004;2(1):13–24.
  18. Barros L., Carvalho A.M., Ferreira I.C.F.R. Leaves, flowers, immature fruits and leafy stems of lemon balm: Nutritional value and antioxidant activity. Food Chemistry. 2010;123(2):388–393.
  19. Perry N.S., Houghton P.J., Sampson J., Theobald A., Hart S., Lis-Balchin M., Hoult J.R.S., Evans P., Jenner P., Milligan S., Perry E.K.
  20. In vitro activity of Melissa officinalis against acetylcholinesterase and its potential use in neurological disorders. Journal of Pharmacy and Pharmacology. 2001;53(10):1347–1356.
  21. Asadi-Samani M, Bahmani M, Rafieian-Kopaei M. Herbal medicine for anxiety: A systematic review. J Evid Based Integr Med. 2016;21(4):242–253.
  22. Shakeri A, Sahebkar A, Javadi B. Melissa officinalis L.—A review of traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2016;188:204–228
  23. Saeb, K. & Gholamrezaee, S. (2012). Variation of essential oil composition of Melissa officinalis L. leaves during different stages of plant growth. Asian Pacific Journal of Tropical Biomedicine, 2(2): 347-349.

Photo
Rathod Lipakshi
Corresponding author

Saraswati Institute of Pharmacy, Kurtadi, Waranga Phata, Hingoli, Maharashtra, India 431701.

Photo
Sakhare Pratik
Co-author

Saraswati Institute of Pharmacy, Kurtadi, Waranga Phata, Hingoli, Maharashtra, India 431701.

Photo
Shaikh Asalamshaha
Co-author

Saraswati Institute of Pharmacy, Kurtadi, Waranga Phata, Hingoli, Maharashtra, India 431701.

Photo
Shinde Jyoti
Co-author

Saraswati Institute of Pharmacy, Kurtadi, Waranga Phata, Hingoli, Maharashtra, India 431701.

Photo
Burkhande Ninad
Co-author

Saraswati Institute of Pharmacy, Kurtadi, Waranga Phata, Hingoli, Maharashtra, India 431701.

Rathod Lipakshi, Sakhare Pratik, Shaikh Asalamshaha, Shinde Jyoti, Burkhande Ninad, A Review on the Extraction, Phytochemistry and Anxiolytic Potential of Melissa officinalis Incorporated Herbal Chocolate, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 4, 3205-3211. https://doi.org/10.5281/zenodo.19673495

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