Contents
What is marjoram
Marjoram (Origanum majorana L.) commonly known as sweet marjoram from the family Lamiaceae, is a perennial herb that 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 1). Marjoram (Origanum majorana L.) grows up to 30 to 60 cm. Marjoram 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 2). In some Middle Eastern countries, marjoram is synonymous with oregano, and there the names sweet marjoram and knotted marjoram are used to distinguish it from other plants of the genus Origanum. Marjoram plant is widely used as a garnish and is used for different medicinal purposes in traditional and folklore medicine of different countries. Sweet marjoram has been used for variety of diseases in traditional and folklore medicines, including ocular disorder, nasopharyngeal disorders, asthma, cold, coughs, cramps, depression, dizziness, gastrointestinal disorders, hay fever, headache, toothache, and sinus congestion and as a diuretic and to promote menstruation 3) and for cardiac, rheumatologic, and neurological disorders 4).
Various compounds have been identified in sweet marjoram. Also, different pharmacological activities have been attributed to this plant. Essential oil containing monoterpene hydrocarbons and oxygenated monoterpenes as well as phenolic compounds are chemical constituents isolated and detected in marjoram. 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 5).
Figure 1. Marjoram (sweet marjoram)
Figure 2. Dried marjoram (marjoram herb)
Marjoram uses
Traditional medicine 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. Marjoram leaves have been claimed to have antimicrobial and emmenagogue (a substance that stimulates or increases menstrual blood flow) properties and be useful for treatment of respiratory and gastrointestinal problems 6). Marjoram has been used in Morocco as an antihypertensive plant 7). The marjoram essential oil has been used for pains, gastrointestinal problems, and respiratory tract disorders 8).
Table 1. Traditional medicine uses of marjoram
| Region | Plant Part Used | Traditional Uses |
|---|---|---|
| Iran 9) | 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 |
| Azerbaijan 10) | Essential oil | Flatulence, nervousness, diuretic, sedative |
| England 11) | Leaves | Cold, bronchial coughs, asthmatic whooping |
| Egypt 12) | Leaves | Cold, chill |
| India 13) | Essential oil | Toothache, soothe joints, muscular pain |
| Austria 14) | Leaves | Gastrointestinal tract diseases, infections |
| Turkey 15) | Essential oil | Asthma, indigestion, headache, rheumatism |
| Morocco 16) | Leaves | Hypertension |
Phytochemical constituents of marjoram
Table 2. Structure and phytochemical category of compounds isolated from different parts of sweet marjoram.
| Compound | Chemical Category | Part/Extract |
|---|---|---|
| α-Pinene | Monoterpene hydrocarbon | Essential oil18) |
| β-Pinene | Monoterpene hydrocarbon | Essential oil19) |
| ρ-Cymene | Monoterpene hydrocarbon | Essential oil20) |
| Camphene | Monoterpene hydrocarbon | Essential oil21) |
| α-Phellandrene | Monoterpene hydrocarbon | Essential oil 22) |
| β-Phellandrene | Monoterpene hydrocarbon | Essential oil 23) |
| γ-Terpinene | Monoterpene hydrocarbon | Essential oil24) |
| d-Limonene | Monoterpene hydrocarbon | Essential oil 25) |
| α-Terpinene | Monoterpene hydrocarbon | Essential oil 26) |
| Terpinolene | Monoterpene hydrocarbon | Essential oil 27) |
| β-Myrcene | Monoterpene hydrocarbon | Essential oil 28) |
| 2-Carene | Monoterpene hydrocarbon | Essential oil 29) |
| β-Ocimene | Monoterpene hydrocarbon | Essential oil 30) |
| Sabinene | Monoterpene hydrocarbon | Essential oil 31) |
| α-Thujene | Monoterpene hydrocarbon | Essential oil 32) |
| Carvone | Monoterpene hydrocarbon | Essential oil 33) |
| Citronellol | Monoterpene hydrocarbon | Essential oil 34) |
| Terpinen-4-ol | Oxygenated monoterpene | Essential oil 35) / Leaf 36) |
| cis-Sabinene hydrate | Oxygenated monoterpene | Essential oil 37) |
| trans-Sabinene hydrate | Oxygenated monoterpene | Essential oil 38) |
| Linalool | Oxygenated monoterpene | Leaf 39) / Essential oil 40) |
| Thymol | Oxygenated monoterpene | Essential oil 41) |
| α-Terpineol | Oxygenated monoterpene | Essential oil 42) |
| Linalyl acetate | Oxygenated monoterpene | Essential oil 43) |
| Carvacrol | Oxygenated monoterpene | Essential oil 44) |
| 1,8-Cineol | Oxygenated monoterpene | Essential oil 45) |
| Fenchyl alcohol | Oxygenated monoterpene | Essential oil 46) |
| Piperitol | Oxygenated monoterpene | Essential oil 47) |
| trans-Carveol | Oxygenated monoterpene | Essential oil 48) |
| cis-Carveol | Oxygenated monoterpene | Essential oil 49) |
| Anethole | Oxygenated monoterpene | Essential oil 50) |
| Geraniol | Oxygenated monoterpene | Essential oil 51) |
| α-Terpinyl acetate | Oxygenated monoterpene | Essential oil 52) |
| Geranyl acetate | Oxygenated monoterpene | Essential oil 53) |
| α-Cubebene | Sesquiterpene hydrocarbon | Essential oil 54) |
| Longicyclene | Sesquiterpene hydrocarbon | Essential oil 55) |
| Copaene | Sesquiterpene hydrocarbon | Essential oil 56) |
| β-Longipinene | Sesquiterpene hydrocarbon | Essential oil 57) |
| β-Caryophyllene | Sesquiterpene hydrocarbon | Essential oil 58) |
| Aromadendrene | Sesquiterpene hydrocarbon | Essential oil 59) |
| α-Humulene | Sesquiterpene hydrocarbon | Essential oil 60) |
| β-Farnesene | Sesquiterpene hydrocarbon | Essential oil 61) |
| Alloaromadendrene | Sesquiterpene hydrocarbon | Essential oil 62) |
| α-Selinene | Sesquiterpene hydrocarbon | Essential oil 63) |
| ar-Curcumene | Sesquiterpene hydrocarbon | Essential oil 64) |
| Germacrene D | Sesquiterpene hydrocarbon | Essential oil 65) |
| Valencene | Sesquiterpene hydrocarbon | Essential oil 66) |
| α-Muurolene | Sesquiterpene hydrocarbon | Essential oil 67) |
| α-Farnesene | Sesquiterpene hydrocarbon | Essential oil 68) |
| Spathulenol | Sesquiterpene alcohol | Essential oil 69) |
| Caryophyllene oxide | Oxygenated sesquiterpene | Essential oil70) |
| Carnosic acid | Diterpenoid | Water extract 71) |
| Carnosol | Diterpenoid | Water extract 72) |
| Ursolic acid | Triterpenoid | Water extract 73) |
| Sinapic acid | Phenolic acid | Essential oil 74) |
| Vanillic acid | Phenolic acid | Hydroalcoholic extract 75) / Essential oil 76) |
| Ferulic acid | Phenolic acid | Hydroalcoholic extract 77) / Essential oil 78) |
| Caffeic acid | Phenolic acid | Hydroalcoholic extract 79) / Essential oil 80) |
| Syringic acid | Phenolic acid | Hydroalcoholic extract 81) / Essential oil 82) |
| ρ-Hydroxybenzoic acid | Phenolic acid | Hydroalcoholic extract 83) / Essential oil 84) |
| m-Hydroxybenzoic acid | Phenolic acid | Hydroalcoholic extract 85) |
| Coumarinic acid | Phenolic acid | Essential oil 86) |
| Gallic acid | Phenolic acid | Hydroalcoholic extract 87) |
| Neochlorogenic acid | Phenolic acid | Hydroalcoholic extract 88) |
| Protocatechuic acid | Phenolic acid | Hydroalcoholic extract 89) |
| Caftaric acid | Phenolic acid | Hydroalcoholic extract 90) |
| Rosmarinic acid | Phenolic acid | Ethyl acetate extract 91) / Essential oil 92) |
| Chlorogenic acid | Phenolic acid | Hydroalcoholic extract 93) |
| Cryptochlorogenic acid | Phenolic acid | Hydroalcoholic extract 94) |
| Coumaric acid | Phenolic acid | Hydroalcoholic extract 95) |
| Lithospermic acid | Phenolic acid | Water extract 96) |
| Methyl rosmarinate | Phenolic compound | Hydrophilic extract 97) |
| Hydroquinone | Phenolic compound | Ethyl acetate extract 98) / Essential oil 99) |
| Arbutin | Phenolic glycosides | Ethyl acetate extract 100) / Essential oil 101) |
| Methyl arbutin | Phenolic glycoside | Essential oil 102) |
| Vitexin | Phenolic glycoside | Essential oil 103) |
| Orientinthymonin | Phenolic glycoside | Essential oil 104) |
| Hesperetin | Flavonoid | Ethyl acetate extract 105) |
| Catechin | Flavonoid | Hydroalcoholic extract 106) |
| Quercetin | Flavonoid | Hydroalcoholic extract 107) |
| Kaempferol | Flavonoid | Hydroalcoholic extract 108) |
| Naringenine | Flavonoid | Hydroalcoholic extract 109) |
| Eriodictyol | Flavonoid | Hydroalcoholic extract 110) |
| Diosmetin | Flavonoid | Essential oil 111) |
| Luteolin | Flavonoid | Essential oil 112) |
| Apigenin | Flavonoid | Essential oil 113) |
| 5,6,3′-Trihydroxy-7,8,4′-trimethoxyflavone | Flavonoid | Ethyl acetate extract 114) |
| Kaempferol-3-O-glucoside | Flavonoid glycoside | Hydroalcoholic extract 115) |
| Quercetin-3-O-glucoside | Flavonoid glycoside | Hydroalcoholic extract 116) |
| Narigenin-O-hexoside | Flavonoid glycoside | Hydroalcoholic extract 117) |
| Apigenin-glucuronide | Flavonoid glycoside | Water extract 118) |
| Rutin | Flavonoid glycoside | Hydroalcoholic extract 119) |
| Luteolin-7-O-β-glucuronide | Flavonoid glycoside | Hydrophilic extract 120) |
| Eugenol | Phenyl propene | Essential oil 121) |
| Ethyl cinnamate | Ester | Essential oil 122) |
| Sitosterol | Phytosterol | Essential oil 123) |
| Oleanolic acid | Fatty acid | Essential oil 124) |
| Vitamin A | Vitamin | Essential oil 125) |
| Vitamin C | Vitamin | Essential oil 126) |
Figure 3. Marjoram active compounds
Marjoram 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 129). 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 130). 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 marjoram10,21 and kaempferol-3-O-glucoside, quercetin-3-O-glucoside, narigenin-O-hexoside, and rutin are flavonoid glycosides identified in sweet marjoram 131).
Antioxidant properties of marjoram
It has been suggested that phenolic compounds from marjoram, such as flavonoids and phenolic acids, might exert anti-inflammatory properties (Table 3) 132). In this regard, Mueller et al. 133) evaluated the anti-inflammatory activity of marjoram hydrophilic extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Pre-treatment of the cells with with the extracts from marjoram at 500 μg/mL and 200 μg/mL the levels of IL-6 were reduced 20% and 17%, respectively, while the iNOS expression was diminished 66%. Even though Mueller et al. 134) did not identify the compounds in the marjoram extracts, they mention that diosmetin, apigenin, luteolin and rosmarinic acid are the compounds to most likely be present in the hydrophilic extracts, so these molecules might be responsible for the activity of marjoram extracts.
Table 3. Summary of the antioxidant capacity of flavonoids and phenolic acids of Marjoram
| Extract | Compounds | Plant Part | Antioxidant Assay | Reference |
| Methanol microwave-assisted | Rosmarinic and caffeic acid, apigenin, rutin | Aerial parts | TPC, DPPH, CUPRAC | 135) |
| Aqueous, methanol | Rosmarinic and caffeic acids | Leaves | TPC, DPPH, β-carotene bleaching | 136) |
| Methanol | Rosmarinic acid, eriodictyol, naringenin, hispidulin, cirsimaritin | Leaves, commercial herbs | TPC, ORAC | 137) |
| Methanol | Rosmarinic acid, epigallocatechin, quercetin, apigenin | Not specified | DPPH, FRAP | 138) |
| Ethanol | Chlorogenic, ferulic, p-coumaric, p-hydroxybenzoic, protocatechuic, rosmarinic and syringic acids, quercetin | Not specified | TPC, DPPH, ABTS | 139) |
Pharmacological Activities of Marjoram
Table 4. Pharmacological properties of marjoram in detail
| harmacological Activity | Plant part / Extract | Method | Result | Active Constituent |
|---|---|---|---|---|
| Antioxidant 141) | 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 |
| Antioxidant 142) | Essential oil | DPPH reduction test | Low antioxidant activity with EC50 values >250μg/mL | — |
| Antioxidant 143) | 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 | — |
| Antioxidant 144) | 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 |
| Antioxidant 145) | 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 |
| Antioxidant 146) | Hydroalcoholic extract | ABTS + radical decolorization and DPPH assay | Significant antioxidant capacity with 0.84 and 0.33 mmol TE/g DW, respectively | Polyphenolic compounds |
| Antioxidant 147) | 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 | — |
| Antioxidant 148) | 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 | — |
| Antioxidant 149) | Water extract | DPPH | High antioxidant capacity | Phenolic compounds |
| Antioxidant 150) | 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 |
| Antioxidant 151) | 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 |
| Antimicrobial 152) | 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 | — |
| Antimicrobial 153) | Essential oil | ND | The most susceptible organisms were Beneckea natriegens, Erwinia carotovora, and Moraxella sp. and Aspergillus niger | — |
| Antimicrobial 154) | 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 | — |
| Antimicrobial 155) | 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 | — |
| Antimicrobial 156) | 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) | — |
| Antimicrobial 157) | 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 |
| Antimicrobial 158) | Essential oil | Microdilution | Inhibitory activity against Staphylococcus aureus and Streptococcus pyogenes with MICs of 125 and 250 μg/mL, respectively | — |
| Antimicrobial 159) | Essential oil | Diffusion assay | Growth inhibitory activity against dermatophytes | — |
| Antimicrobial 160) | Methanol extract of leaves | Zone of inhibition | Inhibitory activity against Escherichia coli with 16 mm diameter zone of inhibition | — |
| Anti-inflammatory 161) | 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 |
| Anticancer 162) | 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 | — |
| Anticancer 163) | 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 | — |
| Anticancer 164) | 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 | — |
| Anticancer 165) | 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 | — |
| Anticancer 166) | 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 |
| Antiplatelet 167) | 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 | — |
| Antiplatelet 168) | 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 |
| Antiulcer 169) | 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 activity 170) | Plant extract | Acid and pepsin secretions in normal Wistar rats | ↑ Basal acid and pepsin secretions | — |
| Cardioprotective activity 171) | 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 activity 172) | 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 activities 173) | Essential oil | ND | IC50 value was 36.40 µg/mL | — |
| Anticholinesterase activity 174) | 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 cycle 175) | 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.
[Source 176)]Antimicrobial Activity
Dried whole marjoram 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 177). 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 178). Methanol extract of sweet marjoram exhibited antimicrobial activity against E, Aspergillus niger, Fusarium solani, and Bacillus subtilis 179). The ethanolic ammonia extract reduced the number of viable Pentatrichomonas hominis trophozoites 180). cis-Sabinene hydrate in essential oil of sweet marjoram have been claimed to be responsible for antibacterial effect 181).
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 182).
Anti-cancer properties of marjoram
Several factors are involved in the onset of cancer such as age, alcohol, cancer-causing substances, diet, hormones, obesity, radiation, tobacco, etc.; and they may play a direct or indirect role in the development and progressions of different types of cancers. The National Cancer Institute 183) states that in test tube and in animal studies have shown that the increased presence of antioxidants prevents free radical damage that has been associated with cancer development. Plant foods are the most significance source of natural antioxidants; from which, flavonoids and phenolic acids have attracted the most attention as potential therapeutic agents against cancer. Shukla and Gupta 184) summarized that the potential anticancer properties of flavonoid and phenolic acid as demonstrated by laboratory studies are due to different mechanisms of action, including antioxidation, induction of detoxification enzymes and inhibition of bioactivation enzymes, estrogenic and anti-estrogenic activity, antiproliferation, cell cycle arrest and apoptosis, promotion of differentiation, regulation of host immune function and inhibition of angiogenesis and metastasis. 5,6,3′-Trihydroxy-7,8,4′-trimethoxyflavone, hesperetin, hydroquinone, arbutin and rosmarinic acid were isolated from the water-soluble ethyl acetate extract of aerial parts of marjoram 185). Hesperetin isolated from Origanum majorana has shown better antiproliferative activity than 5-fluoroacil against Rattus norvegicus brain glioma (C6) and and cervical epithelial carcinoma (HeLa) cell proliferation 186). 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 187). Hesperetin and hydroquinone isolated from sweet marjoram extract have revealed strong antiproliferative activity 188). The results showed that the marjoram extract and isolated compounds exhibited significant antioxidant activities. Hence marjoram plant has the potential to be a natural antioxidant in the food industry and an anticancer drug 189).
Antiplatelet Activity
Methanol extract of sweet marjoram leaves inhibit adhesion of platelet to laminin-coated plate 190) and strongly inhibited platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid, and thrombin. Arbutin is responsible for this activity 191).
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 192).
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 193). Essential oil of sweet marjoram depleted serum marker enzymes and replenished antioxidant status in hepatic of rat 194).
Anticholinesterase inhibitory activity
Essential oil and ethanol extract of sweet marjoram have exhibited acetylcholinesterase (AChE) inhibitor activity 195). Ursolic acid (3 beta-Hydroxyurs-12-en-28-oic acid) is responsible for this effect 196). Acetylcholinesterase (AChE) inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of compound currently approved for the treatment of Alzheimer’s Disease 197). This study 198) demonstrated that the ursolic acid of marjoram appeared to be a potent acetylcholinesterase (AChE) inhibitor in Alzheimer’s Disease.
Regulation of menstrual cycle
Sweet marjoram tea significantly reduced dehydroepiandrosterone-sulphate (DHEA-S) and was useful in treatment of polycystic ovary syndrome 199). Twenty-five patients were assigned to receive marjoram tea or a placebo tea twice daily for 1 month (intervention group: n = 14; placebo group: n = 11) 200). The hormonal and metabolic parameters measured at baseline, as well as after the intervention, were: follicle-stimulating hormone, luteinising hormone, progesterone, oestradiol, total testosterone, dehydroepiandrosterone-sulphate (DHEA-S), fasting insulin and glucose, homeostasis model assessment for insulin resistance and glucose to insulin ratio. Marjoram tea significantly reduced dehydroepiandrosterone-sulphate (DHEA-S) and fasting insulin levels by a mean of 1.4 (0.5) μmol/L and 1.9 (0.8) μU/mL, respectively. In comparison to the placebo group, the change was only significant for DHEA-S but not for insulin. Homeostasis model assessment for insulin resistance was not reduced significantly in the intervention group, although the change was significant compared to the placebo group. The results obtained in the that study show the beneficial effects of marjoram tea on the hormonal profile of polycystic ovary syndrome (PCOS) women because it was found to improve insulin sensitivity and reduce the levels of adrenal androgens. Further research is needed to confirm these results and to investigate the active components and mechanisms contributing to such potential beneficial effects of marjoram herb.
Marjoram 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 marjoram essential oil 201). Terpinene 4-ol and cis-sabinene hydrate are 2 main oxygenated monoterpenes isolated from marjoram 202). Linalool, linalyl acetate, α-terpineol, trans- and cis-carveol, thymol, anethole, geraniol, and carvacrol are other oxygenated compounds identified in essential oil 203) and leaves of marjorama 204).
The analysis of the chemical composition of marjoram essential oil samples obtained from different geographical locations indicates that the biological activity is directly related to the concentration of the marjoram essential oil components, which may vary according to the region 205), 206). Moreover, season, climate, stage of plant development at harvest, and the technique of extraction of the product may influence the quantity of the plant compounds 207).
Fifteen compounds were identified in the marjoram essential oil (Table 5). The most abundant compounds were γ-terpinene (25.73%), α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). This chemical profile is in accordance with what is reported in the literature, with some quantitative variations. Rodrigues et al. 208) and Vági et al. 209) also reported the presence of terpenes as the major components of the marjoram essential oil. Usually, terpinen-4-ol and γ-terpinene are described as the most abundant compounds in marjoram essential oil and sabinene and α-terpinene are also observed 210).
Table 5. Chemical composition of Marjoram essential oil
| Compound | RIa | % |
|---|---|---|
| α-Thujene | 921 | 3.96 |
| α-Pinene | 927 | 1.24 |
| Sabinene | 966 | 10.80 |
| Myrcene | 986 | 2.08 |
| α-Phellandrene | 1000 | 1.70 |
| α-Terpinene | 1012 | 17.35 |
| o-Cymene | 1019 | 2.24 |
| β-Phellandrene | 1023 | 7.05 |
| γ-Terpinene | 1053 | 25.73 |
| Terpinolene | 1082 | 3.76 |
| N.I.b | 1097 | 1.06 |
| Terpinen-4-ol | 1174 | 17.24 |
| Trans-sabinene hydrate acetate | 1248 | 0.13 |
| Linalool acetate | 1251 | 1.38 |
| Terpinenen-4-ol acetate | 1293 | 0.88 |
| (Z)-caryophyllene | 1404 | 2.72 |
| N.I.b | 1480 | 0.67 |
| Total identified | 98.26 |
Note: aRelative retention index experimentally determined against n-alkanes on Durabond-DB5 column. bCompound not identified.
Marjoram essential oil uses
Marjoram essential oil have shown significant results in inhibiting the growth of bacteria and fungi and the synthesis of microbial metabolites 212). Because of its antioxidant effects 213), marjoram essential oil or marjoram extract can be used in the prevention of central nervous system disorders 214). Marjoram essential oil was also able to partially prevent the ethanol-induced decline in sperm quality, testosterone levels, and the weight of reproductive organs in male rats 215). Previous studies have reported the potential use of marjoram ethanolic extract as anticancer agent 216), whereas the marjoram tea extract has been shown to have immunostimulant, antigenotoxic and antimutagenic properties 217). These activities are attributed to the chemical composition, which is characterized as rich in flavonoids and terpenoids – see Tables 2, 3 and 4 above 218).
Marjoram Toxicity
Acute toxicity test has demonstrated a large margin of safety of marjoram extract in mice. Emmenagogue (a substance that stimulates or increases menstrual blood flow) properties of sweet marjoram should be of concerned during pregnancy. Marjoram essential oil must not be used by lactating and pregnant women 219).
Summary
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. 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 marjoram. Figure 3 shows the structure of some main active compounds. Various bioactive compounds have been isolated and identified in O majorana, whereas many active compounds for the traditional medicine uses have not been completely evaluated in clinical trials.
Due to marjoram’s emmenagogue properties, marjoram essential oil must not be used by lactating and pregnant women 220).
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