marjoram

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)

marjoram

Figure 2. Dried marjoram (marjoram herb)

dried marjoramMarjoram 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

RegionPlant Part UsedTraditional Uses
Iran 9)LeavesAntimicrobial, 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 oilFlatulence, nervousness, diuretic, sedative
England 11)LeavesCold, bronchial coughs, asthmatic whooping
Egypt 12)LeavesCold, chill
India 13)Essential oilToothache, soothe joints, muscular pain
Austria 14)LeavesGastrointestinal tract diseases, infections
Turkey 15)Essential oilAsthma, indigestion, headache, rheumatism
Morocco 16)LeavesHypertension
[Source 17)]

Phytochemical constituents of marjoram

Table 2. Structure and phytochemical category of compounds isolated from different parts of sweet marjoram.

CompoundChemical CategoryPart/Extract
α-PineneMonoterpene hydrocarbonEssential oil18)
β-PineneMonoterpene hydrocarbonEssential oil19)
ρ-CymeneMonoterpene hydrocarbonEssential oil20)
CampheneMonoterpene hydrocarbonEssential oil21)
α-PhellandreneMonoterpene hydrocarbonEssential oil 22)
β-PhellandreneMonoterpene hydrocarbonEssential oil 23)
γ-TerpineneMonoterpene hydrocarbonEssential oil24)
d-LimoneneMonoterpene hydrocarbonEssential oil 25)
α-TerpineneMonoterpene hydrocarbonEssential oil 26)
TerpinoleneMonoterpene hydrocarbonEssential oil 27)
β-MyrceneMonoterpene hydrocarbonEssential oil 28)
2-CareneMonoterpene hydrocarbonEssential oil 29)
β-OcimeneMonoterpene hydrocarbonEssential oil 30)
SabineneMonoterpene hydrocarbonEssential oil 31)
α-ThujeneMonoterpene hydrocarbonEssential oil 32)
CarvoneMonoterpene hydrocarbonEssential oil 33)
CitronellolMonoterpene hydrocarbonEssential oil 34)
Terpinen-4-olOxygenated monoterpeneEssential oil 35) / Leaf 36)
cis-Sabinene hydrateOxygenated monoterpeneEssential oil 37)
trans-Sabinene hydrateOxygenated monoterpeneEssential oil 38)
LinaloolOxygenated monoterpeneLeaf 39) / Essential oil 40)
ThymolOxygenated monoterpeneEssential oil 41)
α-TerpineolOxygenated monoterpeneEssential oil 42)
Linalyl acetateOxygenated monoterpeneEssential oil 43)
CarvacrolOxygenated monoterpeneEssential oil 44)
1,8-CineolOxygenated monoterpeneEssential oil 45)
Fenchyl alcoholOxygenated monoterpeneEssential oil 46)
PiperitolOxygenated monoterpeneEssential oil 47)
trans-CarveolOxygenated monoterpeneEssential oil 48)
cis-CarveolOxygenated monoterpeneEssential oil 49)
AnetholeOxygenated monoterpeneEssential oil 50)
GeraniolOxygenated monoterpeneEssential oil 51)
α-Terpinyl acetateOxygenated monoterpeneEssential oil 52)
Geranyl acetateOxygenated monoterpeneEssential oil 53)
α-CubebeneSesquiterpene hydrocarbonEssential oil 54)
LongicycleneSesquiterpene hydrocarbonEssential oil 55)
CopaeneSesquiterpene hydrocarbonEssential oil 56)
β-LongipineneSesquiterpene hydrocarbonEssential oil 57)
β-CaryophylleneSesquiterpene hydrocarbonEssential oil 58)
AromadendreneSesquiterpene hydrocarbonEssential oil 59)
α-HumuleneSesquiterpene hydrocarbonEssential oil 60)
β-FarneseneSesquiterpene hydrocarbonEssential oil 61)
AlloaromadendreneSesquiterpene hydrocarbonEssential oil 62)
α-SelineneSesquiterpene hydrocarbonEssential oil 63)
ar-CurcumeneSesquiterpene hydrocarbonEssential oil 64)
Germacrene DSesquiterpene hydrocarbonEssential oil 65)
ValenceneSesquiterpene hydrocarbonEssential oil 66)
α-MuuroleneSesquiterpene hydrocarbonEssential oil 67)
α-FarneseneSesquiterpene hydrocarbonEssential oil 68)
SpathulenolSesquiterpene alcoholEssential oil 69)
Caryophyllene oxideOxygenated sesquiterpeneEssential oil70)
Carnosic acidDiterpenoidWater extract 71)
CarnosolDiterpenoidWater extract 72)
Ursolic acidTriterpenoidWater extract 73)
Sinapic acidPhenolic acidEssential oil 74)
Vanillic acidPhenolic acidHydroalcoholic extract 75) / Essential oil 76)
Ferulic acidPhenolic acidHydroalcoholic extract 77) / Essential oil 78)
Caffeic acidPhenolic acidHydroalcoholic extract 79) / Essential oil 80)
Syringic acidPhenolic acidHydroalcoholic extract 81) / Essential oil 82)
ρ-Hydroxybenzoic acidPhenolic acidHydroalcoholic extract 83) / Essential oil 84)
m-Hydroxybenzoic acidPhenolic acidHydroalcoholic extract 85)
Coumarinic acidPhenolic acidEssential oil 86)
Gallic acidPhenolic acidHydroalcoholic extract 87)
Neochlorogenic acidPhenolic acidHydroalcoholic extract 88)
Protocatechuic acidPhenolic acidHydroalcoholic extract 89)
Caftaric acidPhenolic acidHydroalcoholic extract 90)
Rosmarinic acidPhenolic acidEthyl acetate extract 91) / Essential oil 92)
Chlorogenic acidPhenolic acidHydroalcoholic extract 93)
Cryptochlorogenic acidPhenolic acidHydroalcoholic extract 94)
Coumaric acidPhenolic acidHydroalcoholic extract 95)
Lithospermic acidPhenolic acidWater extract 96)
Methyl rosmarinatePhenolic compoundHydrophilic extract 97)
HydroquinonePhenolic compoundEthyl acetate extract 98) / Essential oil 99)
ArbutinPhenolic glycosidesEthyl acetate extract 100) / Essential oil 101)
Methyl arbutinPhenolic glycosideEssential oil 102)
VitexinPhenolic glycosideEssential oil 103)
OrientinthymoninPhenolic glycosideEssential oil 104)
HesperetinFlavonoidEthyl acetate extract 105)
CatechinFlavonoidHydroalcoholic extract 106)
QuercetinFlavonoidHydroalcoholic extract 107)
KaempferolFlavonoidHydroalcoholic extract 108)
NaringenineFlavonoidHydroalcoholic extract 109)
EriodictyolFlavonoidHydroalcoholic extract 110)
DiosmetinFlavonoidEssential oil 111)
LuteolinFlavonoidEssential oil 112)
ApigeninFlavonoidEssential oil 113)
5,6,3′-Trihydroxy-7,8,4′-trimethoxyflavoneFlavonoidEthyl acetate extract 114)
Kaempferol-3-O-glucosideFlavonoid glycosideHydroalcoholic extract 115)
Quercetin-3-O-glucosideFlavonoid glycosideHydroalcoholic extract 116)
Narigenin-O-hexosideFlavonoid glycosideHydroalcoholic extract 117)
Apigenin-glucuronideFlavonoid glycosideWater extract 118)
RutinFlavonoid glycosideHydroalcoholic extract 119)
Luteolin-7-O-β-glucuronideFlavonoid glycosideHydrophilic extract 120)
EugenolPhenyl propeneEssential oil 121)
Ethyl cinnamateEsterEssential oil 122)
SitosterolPhytosterolEssential oil 123)
Oleanolic acidFatty acidEssential oil 124)
Vitamin AVitaminEssential oil 125)
Vitamin CVitaminEssential oil 126)
[Source 127)]

Figure 3. Marjoram active compounds

Marjoram active compounds Marjoram active compounds
[Source 128)]

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

ExtractCompoundsPlant PartAntioxidant AssayReference
Methanol microwave-assistedRosmarinic and caffeic acid, apigenin, rutinAerial partsTPC, DPPH, CUPRAC135)
Aqueous, methanolRosmarinic and caffeic acidsLeavesTPC, DPPH, β-carotene bleaching136)
MethanolRosmarinic acid, eriodictyol, naringenin, hispidulin, cirsimaritinLeaves, commercial herbsTPC, ORAC137)
MethanolRosmarinic acid, epigallocatechin, quercetin, apigeninNot specifiedDPPH, FRAP138)
EthanolChlorogenic, ferulic, p-coumaric, p-hydroxybenzoic, protocatechuic, rosmarinic and syringic acids, quercetinNot specifiedTPC, DPPH, ABTS139)
[Source 140)]

Pharmacological Activities of Marjoram

Table 4. Pharmacological properties of marjoram in detail

harmacological ActivityPlant part / ExtractMethodResultActive Constituent
Antioxidant 141)Ethanol, n-hexane, supercritical CO2 and water extract of herbDPPH method and chemiluminometric methodAntioxidant activities of all extractsUrsolic acid, carnosic acid, carnosol
Antioxidant 142)Essential oilDPPH reduction testLow 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-carotene1)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 compoundsDPPHSignificant antioxidant activities from extract and isolated compounds with IC50 of 2.77 and 1.92 µg/mL, respectivelyHydroquinone
Antioxidant 145)Essential oil / Water extractABTS + reducing power were examined for their effect against lipid oxidation in comparison to a tea water extract by measurement of the oil stability indexRemarkable capacity in retarding lipid oxidation with oil stability index 13.9 hoursBound forms of phenolic compounds such as hydroxycinnamic acid and flavonoids
Antioxidant 146)Hydroalcoholic extractABTS + radical decolorization and DPPH assaySignificant antioxidant capacity with 0.84 and 0.33 mmol TE/g DW, respectivelyPolyphenolic compounds
Antioxidant 147)Essential oilGlutathione 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 oilDPPH, .OH, H2O2, reducing power and lipid peroxidationIC50 values of 58.67, 67.11, 91.25, 78.67, and 68.75 µg/mL, respectively
Antioxidant 149)Water extractDPPHHigh antioxidant capacityPhenolic compounds
Antioxidant 150)Isolated metaboliteAmyloid β–induced oxidative injury in PC12 nerve cells by MTT, LDH, and trypan blue assays↓ Amyloid β–induced neurotoxic effectUrsolic acid
Antioxidant 151)Plant extractDPPH and ferric ion reducing antioxidant power assaysA direct, positive, and linear relationship between antioxidant activity and total phenolic content of extractRosmarinic acid
Antimicrobial 152)Dried whole plant/oil/leaves aqueous extractMICBetter 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 oilNDThe most susceptible organisms were Beneckea natriegens, Erwinia carotovora, and Moraxella sp. and Aspergillus niger
Antimicrobial 154)n-Hexane extract, aqueous ethanol, ethanolic ammonia extractDisk-diffusion method for bacteria and serial dilution method for protozoan-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 extractFilter paper disk diffusion methodConsiderable 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 oilAgar diffusion methodActive against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae with inhibition zone of 16, 12, 15, and 13 mm, respectivelycis-Sabinene hydrate
Antimicrobial 158)Essential oilMicrodilutionInhibitory activity against Staphylococcus aureus and Streptococcus pyogenes with MICs of 125 and 250 μg/mL, respectively
Antimicrobial 159)Essential oilDiffusion assayGrowth inhibitory activity against dermatophytes
Antimicrobial 160)Methanol extract of leavesZone of inhibitionInhibitory activity against Escherichia coli with 16 mm diameter zone of inhibition
Anti-inflammatory 161)Essential oilTHP-1 human macrophage cells activated by LPS or human ox-LDL, and the cytokine secretion and gene expression, in vitroSuppression of production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) and COX-2 and NFκB gene expressionSabinene hydrate, terpineol
Anticancer 162)Essential oilMTT assayCytotoxic 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 extractMTT assay, trypan blue dye exclusion, AO/EB staining and fluorescence microscopical analysis and DNA fragmentation analysisSignificant cytotoxic activity of ethanolic extract on fibrosarcoma cancer cell line HT-1080 and least toxicity on normal human lymphocytes
Anticancer  164)Plant extractNonradioactive 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 compoundsBrdU cell proliferation enzyme-linked immunosorbent assay and xCELLigence assay against C6 and HeLa cell linesStrong antiproliferative activities against C6 and HeLa cellsHesperetin, Hydroquinone
Antiplatelet 167)Methanol extract of leavesAdhesion, aggregation and protein secretion of the activated platelet to laminin-coated plates40% inhibition of platelet adhesion to laminin-coated wells by ethanol extract at concentration of 200 µg/mL
Antiplatelet 168)Methanol extractPlatelet aggregation induced by collagen; ADP, arachidonic acid and thrombinStrong inhibition of platelet aggregation induced by ADP, arachidonic acid and thrombinArbutin
Antiulcer 169)Ethanol extractHypothermic 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 extractAcid and pepsin secretions in normal Wistar rats↑ Basal acid and pepsin secretions
Cardioprotective activity 171)Leaves powder and aqueous extractIsoproterenol-induced myocardial infarction in ratsAlleviation 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 oilPralletrin-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 oilNDIC50 value was 36.40 µg/mL
Anticholinesterase activity 174)Ethanol extractIn vitroThe Ki value was 6 pM, and IC50 value was 7.5 nMUrsolic acid
Hormonal activity and regulation of menstrual cycle 175)Water extract25 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

CompoundRIa%
α-Thujene9213.96
α-Pinene9271.24
Sabinene96610.80
Myrcene9862.08
α-Phellandrene10001.70
α-Terpinene101217.35
o-Cymene10192.24
β-Phellandrene10237.05
γ-Terpinene105325.73
Terpinolene10823.76
N.I.b10971.06
Terpinen-4-ol117417.24
Trans-sabinene hydrate acetate12480.13
Linalool acetate12511.38
Terpinenen-4-ol acetate12930.88
(Z)-caryophyllene14042.72
N.I.b14800.67
Total identified98.26

Note: aRelative retention index experimentally determined against n-alkanes on Durabond-DB5 column. bCompound not identified.

[Source 211)]

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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