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Abstract

Origanum majorana L. commonly known as sweet marjoram has been used for variety of diseases in traditional and folklore medicines, including gastrointestinal, ocular, nasopharyngeal, respiratory, cardiac, rheumatologic, and neurological disorders. Essential oil containing monoterpene hydrocarbons and oxygenated monoterpenes as well as phenolic compounds are chemical constituents isolated and detected in O majorana. Wide range of pharmacological activities including antioxidant, hepatoprotective, cardioprotective, anti-platelet, gastroprotective, antibacterial and antifungal, antiprotozoal, antiatherosclerosis, anti-inflammatory, antimetastatic, antitumor, antiulcer, and anticholinesterase inhibitory activities have been reported from this plant in modern medicine. This article summarizes comprehensive information concerning traditional uses, phytochemistry, and pharmacological activities of sweet marjoram.

Keywords

traditional medicine pharmacology phytochemical constituent

Origanum majorana L. from the family Lamiaceae (syn. Majorana hortensis Moench) is commonly known as sweet marjoram. This herb is native to Mediterranean region and cultivated in many countries of Asia, North Africa, and Europe, for example, Spain, Hungary, Portugal, Germany, Egypt, Poland, and France. Origanum majorana grows up to 30 to 60 cm. It is a perennial bushy plant. It has oblique rhizome, hairy shrub like stalks, opposite dark green oval leaves and white or red flowers in clustered bracts. The leaves are whole, larger ones being fragmented, oblate to broadly elliptical.^1
–3 This plant is widely used as a garnish and is used for different medicinal purposes in traditional and folklore medicine of different countries. Various compounds have been identified in sweet marjoram. Also, different pharmacological activities have been attributed to this plant. The present review summarizes comprehensive information concerning traditional uses, phytochemistry, and pharmacological activities of sweet marjoram. For this purpose, databases, including PubMed, Google Scholar, and Scopus were searched for studies focusing on the ethnomedicinal use, phytochemical compounds and pharmacological activities of sweet marjoram. Data were collected from 1980 to 2015 (up to July). The search terms were “sweet marjoram” or “Origanum majorana.”

Ethnomedicinal Uses

Ethnomedicinal uses of sweet marjoram in different countries are shown in Table 1. The parts of sweet marjoram that are used in folklore medicine are dried leaves, leaves extract, and essential oil. Origanum majorana leaves have been claimed to have antimicrobial and emmenagogue properties and be useful for treatment of respiratory and gastrointestinal problems.^1, ^4,5 It has been used in Morocco as an antihypertensive plant.⁸ The essential oil of the plant has been used for pains, gastrointestinal problems, and respiratory tract disorders.^6,8

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Table 1.

Ethnomedicinal Uses of Origanum Majorana.

Region	Plant Part Used	Traditional Uses
Iran^4,5	Leaves	Antimicrobial, antiseptic, antidote, carminative, antitussive and used for gastrointestinal disorder, head cool, sniffle, vision performance, otitis, melancholia accompanied by flatulence, unilateral facial paralysis, headache, epilepsy, cataract, weakness of sight, ear pain, dyspnea, cardiac pain, dysrhythmia, cramp, obstruction of large intestine, emmenagogue, strangury, dropsy, spondilolysthesis, groin pain, back pain, fatigue, freckle, migraine
Azerbaijan⁶	Essential oil	Flatulence, nervousness, diuretic, sedative
England¹	Leaves	Cold, bronchial coughs, asthmatic whooping
Egypt¹	Leaves	Cold, chill
India¹¹	Essential oil	Toothache, soothe joints, muscular pain
Austria⁷	Leaves	Gastrointestinal tract diseases, infections
Turkey⁸	Essential oil	Asthma, indigestion, headache, rheumatism
Morocco⁹	Leaves	Hypertension

Phytochemical Constituents

Table 2 shows the structure and phytochemical category of compounds isolated from different parts of sweet marjoram.

Table 2.

Phytochemical Constituents of Origanum majorana.

Compound	Chemical Category	Part/Extract
α-Pinene	Monoterpene hydrocarbon	Essential oil^2,13
β-Pinene	Monoterpene hydrocarbon	Essential oil^2,13
ρ-Cymene	Monoterpene hydrocarbon	Essential oil^2,14
Camphene	Monoterpene hydrocarbon	Essential oil¹³
α-Phellandrene	Monoterpene hydrocarbon	Essential oil²
β-Phellandrene	Monoterpene hydrocarbon	Essential oil²
γ-Terpinene	Monoterpene hydrocarbon	Essential oil^14 –16
d-Limonene	Monoterpene hydrocarbon	Essential oil¹³
α-Terpinene	Monoterpene hydrocarbon	Essential oil^2,3,15,16
Terpinolene	Monoterpene hydrocarbon	Essential oil²
β-Myrcene	Monoterpene hydrocarbon	Essential oil²
2-Carene	Monoterpene hydrocarbon	Essential oil¹⁷
β-Ocimene	Monoterpene hydrocarbon	Essential oil¹⁷
Sabinene	Monoterpene hydrocarbon	Essential oil^1,16,17
α-Thujene	Monoterpene hydrocarbon	Essential oil²
Carvone	Monoterpene hydrocarbon	Essential oil^2,13
Citronellol	Monoterpene hydrocarbon	Essential oil¹³
Terpinen-4-ol	Oxygenated monoterpene	Essential oil^14 –16,19 / Leaf¹⁸
cis-Sabinene hydrate	Oxygenated monoterpene	Essential oil^10,14,15
trans-Sabinene hydrate	Oxygenated monoterpene	Essential oil^15,16
Linalool	Oxygenated monoterpene	Leaf¹⁸ / Essential oil^1,13
Thymol	Oxygenated monoterpene	Essential oil^10,13,19
α-Terpineol	Oxygenated monoterpene	Essential oil^1 –3,13,15
Linalyl acetate	Oxygenated monoterpene	Essential oil^2,15
Carvacrol	Oxygenated monoterpene	Essential oil^10,13
1,8-Cineol	Oxygenated monoterpene	Essential oil¹⁷
Fenchyl alcohol	Oxygenated monoterpene	Essential oil¹⁷
Piperitol	Oxygenated monoterpene	Essential oil¹⁷
trans-Carveol	Oxygenated monoterpene	Essential oil¹⁷
cis-Carveol	Oxygenated monoterpene	Essential oil¹⁷
Anethole	Oxygenated monoterpene	Essential oil¹⁷
Geraniol	Oxygenated monoterpene	Essential oil¹³
α-Terpinyl acetate	Oxygenated monoterpene	Essential oil²
Geranyl acetate	Oxygenated monoterpene	Essential oil¹⁷
α-Cubebene	Sesquiterpene hydrocarbon	Essential oil¹⁷
Longicyclene	Sesquiterpene hydrocarbon	Essential oil¹⁷
Copaene	Sesquiterpene hydrocarbon	Essential oil¹⁷
β-Longipinene	Sesquiterpene hydrocarbon	Essential oil¹⁷
β-Caryophyllene	Sesquiterpene hydrocarbon	Essential oil¹⁷
Aromadendrene	Sesquiterpene hydrocarbon	Essential oil¹⁷
α-Humulene	Sesquiterpene hydrocarbon	Essential oil¹⁷
β-Farnesene	Sesquiterpene hydrocarbon	Essential oil¹⁷
Alloaromadendrene	Sesquiterpene hydrocarbon	Essential oil¹⁷
α-Selinene	Sesquiterpene hydrocarbon	Essential oil¹⁷
ar-Curcumene	Sesquiterpene hydrocarbon	Essential oil¹⁷
Germacrene D	Sesquiterpene hydrocarbon	Essential oil¹⁷
Valencene	Sesquiterpene hydrocarbon	Essential oil¹⁷
α-Muurolene	Sesquiterpene hydrocarbon	Essential oil¹⁷
α-Farnesene	Sesquiterpene hydrocarbon	Essential oil¹⁷
Spathulenol	Sesquiterpene alcohol	Essential oil²
Caryophyllene oxide	Oxygenated sesquiterpene	Essential oil^2,17
Carnosic acid	Diterpenoid	Water extract²⁰
Carnosol	Diterpenoid	Water extract²⁰
Ursolic acid	Triterpenoid	Water extract²⁰
Sinapic acid	Phenolic acid	Essential oil¹
Vanillic acid	Phenolic acid	Hydroalcoholic extract²¹ / Essential oil¹
Ferulic acid	Phenolic acid	Hydroalcoholic extract²¹ / Essential oil¹
Caffeic acid	Phenolic acid	Hydroalcoholic extract²¹ / Essential oil^1,22
Syringic acid	Phenolic acid	Hydroalcoholic extract²¹ / Essential oil¹
ρ-Hydroxybenzoic acid	Phenolic acid	Hydroalcoholic extract²¹ / Essential oil¹
m-Hydroxybenzoic acid	Phenolic acid	Hydroalcoholic extract²¹
Coumarinic acid	Phenolic acid	Essential oil¹
Gallic acid	Phenolic acid	Hydroalcoholic extract²¹
Neochlorogenic acid	Phenolic acid	Hydroalcoholic extract²¹
Protocatechuic acid	Phenolic acid	Hydroalcoholic extract²¹
Caftaric acid	Phenolic acid	Hydroalcoholic extract²¹
Rosmarinic acid	Phenolic acid	Ethyl acetate extract⁸ / Essential oil²²
Chlorogenic acid	Phenolic acid	Hydroalcoholic extract²¹
Cryptochlorogenic acid	Phenolic acid	Hydroalcoholic extract²¹
Coumaric acid	Phenolic acid	Hydroalcoholic extract²¹
Lithospermic acid	Phenolic acid	Water extract²³
Methyl rosmarinate	Phenolic compound	Hydrophilic extract²⁴
Hydroquinone	Phenolic compound	Ethyl acetate extract⁸ / Essential oil¹⁰
Arbutin	Phenolic glycosides	Ethyl acetate extract⁸ / Essential oil^10,25
Methyl arbutin	Phenolic glycoside	Essential oil¹⁰
Vitexin	Phenolic glycoside	Essential oil¹⁰
Orientinthymonin	Phenolic glycoside	Essential oil¹⁰
Hesperetin	Flavonoid	Ethyl acetate extract⁸
Catechin	Flavonoid	Hydroalcoholic extract²¹
Quercetin	Flavonoid	Hydroalcoholic extract²¹
Kaempferol	Flavonoid	Hydroalcoholic extract²¹
Naringenine	Flavonoid	Hydroalcoholic extract²¹
Eriodictyol	Flavonoid	Hydroalcoholic extract²¹
Diosmetin	Flavonoid	Essential oil¹⁰
Luteolin	Flavonoid	Essential oil¹⁰
Apigenin	Flavonoid	Essential oil¹⁰
5,6,3′-Trihydroxy-7,8,4′-trimethoxyflavone	Flavonoid	Ethyl acetate extract⁸
Kaempferol-3-O-glucoside	Flavonoid glycoside	Hydroalcoholic extract²¹
Quercetin-3-O-glucoside	Flavonoid glycoside	Hydroalcoholic extract²¹
Narigenin-O-hexoside	Flavonoid glycoside	Hydroalcoholic extract²¹
Apigenin-glucuronide	Flavonoid glycoside	Water extract²³
Rutin	Flavonoid glycoside	Hydroalcoholic extract²⁶
Luteolin-7-O-β-glucuronide	Flavonoid glycoside	Hydrophilic extract²⁴
Eugenol	Phenyl propene	Essential oil¹³
Ethyl cinnamate	Ester	Essential oil¹³
Sitosterol	Phytosterol	Essential oil¹⁰
Oleanolic acid	Fatty acid	Essential oil¹⁰
Vitamin A	Vitamin	Essential oil¹
Vitamin C	Vitamin	Essential oil¹

Essential Oil

Monoterpene hydrocarbons, including α and β-pinene, camphene, sabinene, α- and β- phellandrene, ρ-cymene, limonene, β-ocimene, γ-terpinene, terpinolene, α-terpinene, carvone, and citronellol have been detected in essential oil of O majorana.^2,13,14 Terpinene 4-ol and cis-sabinene hydrate are 2 main oxygenated monoterpenes isolated from O majorana.^14,15 Linalool, linalyl acetate, α-terpineol, trans- and cis-carveol, thymol, anethole, geraniol, and carvacrol are other oxygenated compounds identified in essential oil and leaves¹⁸ of O majorana.^13,15,17

Phenolic Compounds

Vanillic acid, gallic acid, ferulic acid, caffeic acid, syringic acid, p- and m-Hydroxybenzoic acid, coumaric acid, neochlorogenic acid, protocatechuic acid, chlorogenic acid, cryptochlorogenic acid, caftaric acid are phenolic acids that have been detected in hydroalcoholic extract of leaves of sweet marjoram.²¹ Rosmarinic acid, sinapic acid, vanillic acid, ferulic acid, caffeic acid, syringic acid, p- and m-hydroxybenzoic acid, and coumarinic acid have been identified in essential oil of sweet marjoram.^1,22 Arbutin, methyl arbutin, vitexin, and orientinthymonin have been reported to be the most predominant phenolic glycosides in essential oil of sweet marjoram.¹⁰ Hesperetin, catechin, quercetin, kaempferol, naringenine, eriodictyol, diosmetin, luteolin, and apigenin are the most abundant flavonoids detected in sweet marjoram^10,21 and kaempferol-3-O-glucoside, quercetin-3-O-glucoside, narigenin-O-hexoside, and rutin are flavonoid glycosides identified in sweet marjoram.^21,26,27

Pharmacological Activities

Table 3 shows pharmacological properties of O majorana in detail.

Table 3.

Pharmacological Properties of Origanum majorana in Detail.

Pharmacological Activity	Plant part / Extract	Method	Result	Active Constituent
Antioxidant²⁰	Ethanol, n-hexane, supercritical CO₂ and water extract of herb	DPPH method and chemiluminometric method	Antioxidant activities of all extracts	Ursolic acid, carnosic acid, carnosol
Antioxidant¹⁹	Essential oil	DPPH reduction test	Low antioxidant activity with EC50 values >250μg/mL	—
Antioxidant¹⁷	Essential oil	(1) DPPH assay (2) Percent inhibition in linoleic acid system (3) Bleaching of β-carotene	1)IC50 of 89.2 µg/ml 2) 72.8% inhibition of linoleic acid oxidation 3)showed slow rate of color depletion	—
Antioxidant⁸	Ethyl acetate extract and isolated compounds	DPPH	Significant antioxidant activities from extract and isolated compounds with IC50 of 2.77 and 1.92 µg/mL, respectively	Hydroquinone
Antioxidant²²	Essential oil / Water extract	ABTS + reducing power were examined for their effect against lipid oxidation in comparison to a tea water extract by measurement of the oil stability index	Remarkable capacity in retarding lipid oxidation with oil stability index 13.9 hours	Bound forms of phenolic compounds such as hydroxycinnamic acid and flavonoids
Antioxidant²¹	Hydroalcoholic extract	ABTS + radical decolorization and DPPH assay	Significant antioxidant capacity with 0.84 and 0.33 mmol TE/g DW, respectively	Polyphenolic compounds
Antioxidant²⁸	Essential oil	Glutathione level and lipid peroxidation content as malondialdehyde in the testis, liver and brain in ethanol treatment male albino rat (ethanol induced reproductive disturbances and oxidative damage in different organs and lipid peroxidation due to the formation of free radicals)	Co-administration of the extract resulted in minimizing the hazard effects of ethanol toxicity on male fertility, liver and brain tissues	—
Antioxidant¹⁶	Essential oil	DPPH, .OH, H₂O₂, reducing power and lipid peroxidation	IC50 values of 58.67, 67.11, 91.25, 78.67, and 68.75 µg/mL, respectively	—
Antioxidant²⁹	Water extract	DPPH	High antioxidant capacity	Phenolic compounds
Antioxidant³⁰	Isolated metabolite	Amyloid β–induced oxidative injury in PC12 nerve cells by MTT, LDH, and trypan blue assays	↓ Amyloid β–induced neurotoxic effect	Ursolic acid
Antioxidant³¹	Plant extract	DPPH and ferric ion reducing antioxidant power assays	A direct, positive, and linear relationship between antioxidant activity and total phenolic content of extract	Rosmarinic acid
Antimicrobial¹⁸	Dried whole plant/oil/leaves aqueous extract	MIC	Better antimicrobial activity of essential oil rather than water extract; inhibition of yeast and lactic acid bacteria by essential oil at a concentration of 5 ppm	—
Antimicrobial³²	Essential oil	ND	The most susceptible organisms were Beneckea natriegens, Erwinia carotovora, and Moraxella sp. and Aspergillus niger	—
Antimicrobial²⁶	n-Hexane extract, aqueous ethanol, ethanolic ammonia extract	Disk-diffusion method for bacteria and serial dilution method for protozoa	n-Hexane extract showed the highest antibacterial activity and the ethanolic ammonia extract reduced the number of viable Pentatrichomonas hominis trophozoites by 50% at 160 µg/ml	—
Antimicrobial³³	Methanol extract	Filter paper disk diffusion method	Considerable activity against Aspergillus niger, Fusarium solani, and Bacillus subtilis with zone of inhibition 40, 28 and 42 mm, respectively	—
Antimicrobial¹⁷	Essential oil	(1) Disk diffusion (2) Resazurin microtitre-plate	(1) Large zone of inhibition (16.5-27.0 mm) (2) Small MIC against Staphylococcus aureus, Bacillus cereus, B subtilis, Pseudomonas aeruginosa, Salmonella poona, Escherichia coli (40.9-1250.3 μg/mL)	—
Antimicrobial¹⁵	Essential oil	Agar diffusion method	Active against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae with inhibition zone of 16, 12, 15, and 13 mm, respectively	cis-Sabinene hydrate
Antimicrobial¹⁹	Essential oil	Microdilution	Inhibitory activity against Staphylococcus aureus and Streptococcus pyogenes with MICs of 125 and 250 μg/mL, respectively	—
Antimicrobial¹⁹	Essential oil	Diffusion assay	Growth inhibitory activity against dermatophytes	—
Antimicrobial³⁴	Methanol extract of leaves	Zone of inhibition	Inhibitory activity against Escherichia coli with 16 mm diameter zone of inhibition	—
Anti-inflammatory³⁵	Essential oil	THP-1 human macrophage cells activated by LPS or human ox-LDL, and the cytokine secretion and gene expression, in vitro	Suppression of production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) and COX-2 and NFκB gene expression	Sabinene hydrate, terpineol
Anticancer¹⁷	Essential oil	MTT assay	Cytotoxic effect against different cancer cell type, such as MCF-7, LNCaP, NIH-3T3 with IC50 s of 70.0, 85.3, 300.5 µg/ml respectively	—
Anticancer³⁶	Ethanol, methanol and water extract	MTT assay, trypan blue dye exclusion, AO/EB staining and fluorescence microscopical analysis and DNA fragmentation analysis	Significant cytotoxic activity of ethanolic extract on fibrosarcoma cancer cell line HT-1080 and least toxicity on normal human lymphocytes	—
Anticancer³⁷	Plant extract	Nonradioactive cytotoxicity assay on human lymphoblastic leukemia cell line Jurkat	↓ Viability of cells with increase of concentration of plant extract. Induction of apoptosis through upregulation of p53 protein levels and downregulation of Bcl-2α. Strong radical scavenging activity	—
Anticancer³⁸	Ethanol extract	(1) Matrigel invasion assays (2) Gelatin zymography assay (3) Chick embryo tumor growth assay	(1) Significant inhibition of migration and invasion of the MDA-MB-231 cells. Induction of homotypic aggregation of cells associated with an up regulation of E-cadherin protein and decrease the adhesion of cells to HUVECs and inhibition of transendothelial migration of cells through TNF-α-activated HUVECs (2) Suppression of activities of MMP-2 and MMP-9 (3) Inhibition of tumor growth and metastasis	—
Anticancer⁸	Ethyl acetate extract and isolated compounds	BrdU cell proliferation enzyme-linked immunosorbent assay and xCELLigence assay against C6 and HeLa cell lines	Strong antiproliferative activities against C6 and HeLa cells	Hesperetin, Hydroquinone
Antiplatelet¹²	Methanol extract of leaves	Adhesion, aggregation and protein secretion of the activated platelet to laminin-coated plates	40% inhibition of platelet adhesion to laminin-coated wells by ethanol extract at concentration of 200 µg/mL	—
Antiplatelet³⁹	Methanol extract	Platelet aggregation induced by collagen; ADP, arachidonic acid and thrombin	Strong inhibition of platelet aggregation induced by ADP, arachidonic acid and thrombin	Arbutin
Antiulcer²⁷	Ethanol extract	Hypothermic restraint stress-, indomethacin-, and necrotizing agents–induced ulcers and pylorus ligated Shay rat-model	↓ Incidence of ulcers, basal gastric secretion and acid output. replenishment of the depleted gastric wall mucus and nonprotein sulfhydryls contents and ↓ malondialdehyde	—
Gastric secretory activity⁴⁰	Plant extract	Acid and pepsin secretions in normal Wistar rats	↑ Basal acid and pepsin secretions	—
Cardioprotective activity⁴¹	Leaves powder and aqueous extract	Isoproterenol-induced myocardial infarction in rats	Alleviation of erythrocytosis, granulocytosis, thrombocytosis, ↓ clotting time, ↑ relative heart weight, ↓ myocardial oxidative stress and the leakage of heart enzymes. inhibition of NO production and lipid peroxidation in heart tissues	—
Hepatoprotective activity¹⁰	Essential oil	Pralletrin-induced oxidative stress in rats (prallethrin caused a significant decrease in the activity of SOD, CAT, and GST in liver of rats)	Depletion of serum marker enzymes and replenishment of antioxidative status	—
Antiacetylcholinesterase activities¹⁶	Essential oil	ND	IC50 value was 36.40 µg/mL	—
Anticholinesterase activity⁴²	Ethanol extract	In vitro	The Ki value was 6 pM, and IC50 value was 7.5 nM	Ursolic acid
Hormonal activity and regulation of menstrual cycle⁴³	Water extract	25 patients were received marjoram tea or a placebo tea twice daily for 1 month. Hormonal and metabolic parameters measured, including FSH, LH, progesterone, oestradiol, total testosterone, DHEA-S, fasting insulin and glucose	↓ DHEA-S and fasting insulin levels	—

Abbreviations: ABTS: 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); ADP, adenosine diphosphate; CAT, catalase; COX, cyclooxygenase; DHEA-S, dehydroepiandrosterone-sulfate; DPPH, 1,1-diphenyl-2-picryl-hydrazyl; DW, dry weight; EC, effective concentration; FSH, follicle-stimulating hormone; GSH, glutathione S-transferase; IC, inhibitory concentration; IL, interleukin; LDH, lactate dehydrogenase; LH, luteinizing hormone; MIC, minimum inhibitory concentration; MMP, matrix metalloproteinase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ND, not determined; NO, nitric oxide; PCOS, polycystic ovary syndrome; SOD, superoxide dismutase; TE, trolox equivalent; TNF, tumor necrosis factor.

Antioxidant Activity

Water extract, essential oil, and ethyl acetate extract of aerial part of O majorana show significant antioxidant activity.^{8,16,17,22,29} Antioxidant properties were also reported from other extracts of sweet marjoram, including ethanolic, n-hexane, and hydroalcoholic extracta.²⁰ Phenolic compounds such as hydroxycinnamic acid and flavonoids, ursolic acid, carnosic acid, carnosol, rosmarinic acid, and caffeic acid are responsible for antioxidant activity.^20,22,30,31

Antimicrobial Activity

Dried whole plant and its essential oil and water extract of leaves have demonstrated antimicrobial effect and essential oil was more active against lactic acid bacteria and yeasts than water extract.¹⁸ Essential oil showed inhibitory activity against various pathogenic bacteria and fungi, including Beneckea natriegens, Erwinia carotovera, Moraxella, Aspergillus, Staphylococcus aureus, Streptococcus pyogenes, Bacillus cereus, B subtilis, Pseudomonas aeruginosa, Salmonella poona, Escherichia coli, and dermatophytes.^15,17,19,32 Methanol extract of sweet marjoram exhibited antimicrobial activity against E, Aspergillus niger, Fusarium solani, and Bacillus subtilis.^33,34 The ethanolic ammonia extract reduced the number of viable Pentatrichomonas hominis trophozoites.²⁶ cis-Sabinene hydrate in essential oil of sweet marjoram have been claimed to be responsible for antibacterial effect.¹⁵

Anti-inflammatory Activity

Sabinene hydrate and terpineol in essential oil of sweet marjoram suppressed the production of Tumor necrosis factor-α (TNFα), interleukin 1β (IL-1β), IL-6, and IL-10 inhibited cyclooxygenase 2 (COX2) and NFκB gene expression.³⁵

Anticancer and Antiproliferative Properties

Ethanol extract of plant have shown significant cytotoxicity against fibrosarcoma cancer cell line, promoting cell cycle arrest and apoptosis of the metastatic breast cell and inhibited the migration and invasion of the MDA-MB-231 cells.^36,38 Ethyl acetate extract have strong antiproliferative activities against C6 and HeLa cells. Hesperetin and hydroquinone isolated from sweet marjoram extract have revealed strong antiproliferative activity.⁸

Antiplatelet Activity

Methanol extract of sweet marjoram leaves inhibit adhesion of platelet to laminin-coated plate¹² and strongly inhibited platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid, and thrombin. Arbutin is responsible for this activity.³⁹

Antiulcerogenetic Effect

Ethanol extract of sweet marjoram significantly decreased the incidence of ulcers, basal gastric secretion, and acid output and replenished the depleted gastric wall mucus.²⁷

Cardioprotective and Hepatoprotective Activity

Leave powder and extract significantly alleviated erythrocytosis, granulocytosis, thrombocytosis, increase heart weight, and myocardial infarction oxidative stress in isoproterenol treated albino rats.⁴¹ Essential oil of sweet marjoram depleted serum marker enzymes and replenished antioxidant status in hepatic of rat.¹⁰

Anticholinesterase Inhibitory Activity

Essential oil and ethanol extract of sweet marjoram have exhibited anticholinesterase inhibitory activity.¹⁶ Ursolic acid is responsible for this effect.⁴²

Regulation of Menstrual Cycle

Sweet marjoram tea significantly reduced dehydroepiandrosterone-S (DHEA-S) and was useful in treatment of polycystic ovary syndrome.⁴³

Toxicity

Acute toxicity test has demonstrated a large margin of safety of O majorana extract in mice. Emmenagogue properties of sweet marjoram should be concerned during pregnancy.¹¹ Its essential oil must not be used by lactating and pregnant women.⁴⁴

Conclusion

Sweet marjoram is a medicinal plant with various proven pharmacological properties, including antioxidant, antibacterial, hepatoprotective, cardioprotective, antiulcer, anticoagulant, anti-inflammatory, antiproliferative, and antifungal activities. The flowering stems are the medicinal parts. Their constituents include 1% to 2% of an essential oil with a containing terpinenes and terpinols, plus tannins, bitter compounds, carotenes, and vitamin C. These substances give sweet marjoram stomachic, carminative, antispasmodic, and weak sedative properties.

In herbalism, it is used mainly for various gastrointestinal disorders and to aid digestion. Novel investigations showed increase in acid and pepsin secretions by this plant. Also sweet marjoram showed antiulcer activity and mucus protecting effects in gastrointestinal tract. Ethnomedicinal use of O majorana on vaginitis and polycystic ovarian disease can be related to restoration of hormonal balance and reduction of DHEA-S by this plant. Efficacious uses of O majorana in cardiac disease and dysrhythmia were proved which may be related to its antiplatelet and cardioprotective activities through inhibition of production of nitric oxide and lipid peroxidation in heart tissues. Useful effect on head cool, sniffle, ear pain, and respiratory disorders may be related to its antimicrobial effect. Monoterpene hydrocarbons (such as α-pinene, β-pinene, camphene, and γ-terpinene), oxygenated monoterpenes particularly terpinene-4-ol, cis-sabinene hydrate and terpineol, phenolic compounds particularly flavonoids (such as apigenin, hesperetin, quercetin, kaempferol), and phenolic glycosides (such as arbutin) are the active components isolated and detected in O majorana. Figure 1 shows the structure of some main active compounds. Various bioactive compounds have been isolated and identified in O majorana, whereas many active compounds responsible for ethnomedicinal uses or proved pharmacological activities have not been completely evaluated. Therefore, new investigations are proposed to isolate, identify and obtain the O majorana active compounds in order to explore novel natural component for rectifying the stalemate on the way of modern medicine.

Figure 1.

The structure of some main active compounds of Origanum majorana.

Footnotes

Author Contributions

RR designed the study and edited the manuscript. FB collected data and wrote the manuscript.

Ethical Approval

This study did not need ethical approval as no animal or human subjects were involved.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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Sweet Marjoram