INTRODUCTION
Oregano, scientifically named Origanum vulgare by Carolus Linnaeus, is a common species of Origanum, a genus of the mint family (Lamiaceae).
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It is native to warm-temperate western and southwestern Eurasia and the Mediterranean region.
Oregano is a perennial herb, growing from 20–80 cm tall, with opposite leaves 1–4 cm long. Oregano will grow in a pH range between 6.0 (mildly acid) and 9.0 (strongly alkaline) with a preferred range between 6.0 and 8.0. The flowers are purple, 3–4 mm long, produced in erect spikes.
The oregano family: Labiatae/Lamiaceae is widely known as possessing therapeutic properties (diaphoretic, carminative, antispasmodic, antiseptic, tonic), being used in the traditional medicine systems of many countries.
CHEMICAL COMPOSITION of oregano essential oil
Sixty-four compounds were identified in the essential oil.
Several studies show that the content of every component may vary considerably among different populations: numerous differences have been found in chemistry of O. vulgare essential oil depending not only on subspecies but also country of origin.
Main components
- Monoterpene hydrocarbons:
- Oxygenated monoterpenes:
- Phenol content:
- Sesquiterpene hydrocarbons:
- Oxygenated sesquiterpenes:
- Polyphenolic glycosides:
- 4-(3,4-Dihydroxybenzoyloxymethyl)phenyl-O-β-d-glucopyranoside (DBPG)
Other components are rosmarinic acid, luteolin-7-O-glucuronide as well as luteolin and different phenolic acids including syringic, protocatechuic, homovanillic, chlorogenic, hydroxybenzoic, caffeic acid, taxifolin, eriodictyol, apigenin.
Chemical composition and biological activity of essential oils of Origanum vulgare L. subsp. vulgare L. under different growth conditions, 2013.
Variability of Essential Oil Content and Composition of Origanum vulgare L. Populations from a North Mediterranean Area (Liguria Region, Northern Italy), 2000
ANTIMICROBIAL ACTIVITY
The antibacterial activity of oregan essential oil can is due to the presence of some phenolic components, especially thymol and carvacrol.
The antibacterial activity of carvacrol has been attributed to its considerable effects on the structural and functional properties of the cell membrane. Due to its hydrophobic nature, carvacrol interacts with the lipid bilayer of the cytoplasmatic membrane and itself aligns between the fatty acid chains causing the expansion and destabilization of the membrane structure and increasing its fluidity and permeability. At sublethal concentrations, carvacrol changes the fatty acid compositions of the cytoplasmatic membrane in different microorganisms increasing the unsaturated fatty acid content.
It is relevant to note that carvacrol is a volatile molecule which evaporates easily and its vapor phase has shown antimicrobial activity. This suggests interesting applicative prospects. In this context, has been reported the efficacy of carvacrol vapor against food-borne bacteria Escherichia coli O157:H7 and Salmonella on the surface of freshly produced vegetables such as lettuce, spinach and tomatoes.
Another study shows the inhibition of Salmonella enterica on raw chicken.
Carvacrol is effective against respiratory tract pathogens such as Hemophilus infuenzae, Streptococcus pneumoniae and Streptococcus pyogenes.
Its activity is extended to drug-resistant microorganisms, strains with a particular significance for pathogenesis as currently are difficult to treat. For example, the activity of this molecule against nosocomial pathogens such as Staphylococcus aureus and S. epidermidis methicillin-resistant is relevant.
The antibacterial activity was evaluated by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) using the broth dilution method.
Carvacrol and thymol also show strong fungicidal effect against all of the Candida albicans isolates. The mechanisms of action appear to originate from the inhibition of ergosterol biosynthesis and the disruption of membrane integrity.
Carvacrol alone or associated with one or more synergistic products could be incorporated in different formulations for biomedical and food packaging applications.
Antimicrobial activity of carvacrol: current progress and future prospectives. 2012.
Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida 2011.
ORIGANUM VULGARE AND HELICOBACTER PYLORI
Helicobacter pylori is associated with gastric ulcers in humans. Current therapies using antibiotics are expensive and have the potential for the development of antibiotic resistance. Therefore, dietary sources have the potential to help the elimination H. pylori.
In several studies was investigated the ability of high phenolic clonal oregano to inhibit the growth of H. pylori.
These antioxidants may act in synergy and inhibit the growth of H. pylori by various mechanisms such as cytosolic hyperacidity, disruption of electron transport chain, membrane destabilization, disruption of membrane transport, inhibition of H+-ATPase, ion channels, and inhibit bacterial metabolism.
The identification of an elite phenolic clonal line will allow the development of dietary phenolic ingredients whose antioxidant potential could enhance protective host defence responses in humans and at the same time inhibit prokaryotic pathogenic bacteria like H. pylori linked to gastric infections.
Phenolic antioxidants from clonal oregano (Origanum vulgare) with antimicrobial activity against Helicobacter pylori, 2005.
ANTIOXIDANT ACTIVITY
Oxidative stress is a cellular imbalance between the production and elimination of reactive oxygen species (ROS) such as superoxide anion radicals (O2•–), hydrogen peroxide (H2O2), and hydroxyl radicals (OH•). It is also a pathophysiological reaction highly relevant to a variety of pathological processes, including ischemia–reperfusion injury, chronic progressive neurodegenerative disease, numerous inflammatory diseases, and cancer. Oxidative stress results in skin aging and can adversely affect skin health.
Origanum vulgare has been shown to contain natural antioxidants that provide protections against harmful free radicals and antagonize the deleterious action of ROS on bioactive molecules.
In a lot of studies several phenolic compounds isolated from O.vulgare were evaluated for their in vitro antioxidant activity using DPPH assay and superoxide radical (O (2)•(-)) assay.
Has been demonstrated that 4-(3,4-Dihydroxybenzoyloxymethyl) phenyl-O-β-d-glucopyranoside (DBPG), a polyphenolic glycoside, isolated from Origanum vulgare has a strong antioxidant activity and DPPH•-scavenging capacity.
The electron-donating abilities of DBPG and L-ascorbic acid (AA) determined by examining the reduction of DPPH• and superoxide radical with increasing concentrations of DBPG and AA are shown in the figure below.
| Free radical scavenging activities and reducing power of DBPG: DPPH• radical scavenging capacities of several concentrations (0, 5, 10, 50, 100, and 200 μM) of DBPG and AA (L-ascorbic acid) and O2•– scavenging abilities of DBPG, trolox, and rutin (0, 5, 10, 50, 100, and 200 μM). |
Although the free radical scavenging activity of DBPG was weaker than that of L-ascorbic acid (AA), DBPG and AA showed similar effects on the scavenging of free radicals at the high concentration (200 μM).
DBPG inhibited the activity of O2•– in a dose-dependent manner. O2•–, molecular oxygen, just reduced to have one extra electron, is one of the most representative free radicals.
Moreover, in a model system based on liposomes, has been observed that DBPG is able to inhibit lipid peroxidation more effectively than L-ascorbic acid.
Lipid peroxidation is recognized as a potential mechanism of injury to liver mitochondria, microsomes, and splenic lymphocytes.
Products of LP, such as malondialdehyde (MDA), form adducts with cellular DNA.
The capacity of DBPG to inhibit LP in a liposome model system was evaluated by measuring the MDA content. As presented in the figure below, the inhibition of LP by DBPG was much weaker than that by trolox, but the inhibition of LP by DBPG exceeded that by AA.
The final stable aldehyde products of peroxidation, TBARS, are generated by the breakdown of peroxides and are critical indicators of cellular damage.
The inhibition of the formation of TBARS provides good evidence for the inhibition of LP by a compound. The reductions of TBARS content by DBPG of 20, 50, and 100 μM were 52.1, 75.9, and 80.4% in mouse liver tissue and were 43.2, 73.5, and 77.0% in mouse brain tissue, respectively (Figure). Adding DBPG to mouse liver and brain tissue inhibited the formation of TBARS to a greater extent than did trolox, a soluble offshoot of E vitamin. These results suggest that the antioxidant properties of DBPG may involve the inhibition of LP, one of the most important antioxidant characteristics of DBPG.
| Inhibition of LP formation by DBPG: (A) inhibition of LP formation in Fe2+/ascorbate system by increasing doses of DBPG, AA, and trolox (0, 5, 10, 50, 100, and 200 μM), using liposomes as an oxidizable substrate; (B) extent of formation of TBARS following incubation of DBPG and trolox (20, 50, and 100 μM) with mouse liver and brain homogenates. |
In the oxygen stress test, BNLCL2 (mouse hepatocytes) and HaCaT (human skin keratinocytes) cells pretreated with DBPG showed increased activities of glutathione peroxidase (GPx), perhaps as a result of reduction of the production of reactive oxygen species (ROS).
These findings proved that DBPG had antioxidant activities and a cytoprotective effect in hepatocytes and keratinocytes, suggesting that DBPG may be a useful food and cosmetic additive.
Free radical scavenging activity of 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside from Origanum vulgare and its protection against oxidative damage. 2012.
ANTITUMOR ACTIVITY
Most chronic diseases, including cancer, arise as a result of dysregulation in multiple cell signaling pathways.
One such critical signaling molecule is transcription factor STAT3, that is often persistently active in various human cancers and regulates the expression of multiple genes involved in initiation, progression and chemoresistance.
Small molecule inhibitors of STAT3 activation have the potential for both prevention and treatment of cancer: β-caryophyllene oxide (CPO), a sesquiterpene isolated primarily from the essential oils of Origanum vulgare and other medicinal plants, can mediate its effect through interference with the STAT3 activation pathway in cancer cells.
CPO suppresses constitutive STAT3 activation in multiple myeloma (MM), breast and prostate cancer cell lines (but also liver, and lung adenocarcinoma), with a significant dose- and time-dependent effects observed in MM cells.
CPO can indeed suppress both constitutive as well as inducible STAT3 expression in tumor cells. This inhibition decreased cell survival and downregulated expression of various proliferative( cyclinD1 ), anti-apoptotic(*bcl-2, bcl-xL, survivin, IAP-1*, and IAP-2), and angiogenic ( VEGF ) gene products, leading to suppression of proliferation, induction of apoptosis, and suppression of invasion in tumor cells.
Immunocytochemistry clearly demonstrates that CPO reduced the translocation of STAT3 into the nucleus and inhibits binding of STAT3 to the DNA. It suppresses also the constitutive activation of JAK2, the constitutive phosphorylation of Src kinase and inhibits IL-6, a growth factor that induces STAT3 and Src phosphorylation.
On the other side CPO Induces the expression of SHP-1, a nontransmembrane protein tyrosine phosphatase expressed in most cells that is important in the negative regulation of JAK/STAT signaling and is often silenced by methylation in leukemias and lymphomas.
Both PI3K/AKT/mTOR/S6K1 and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis, and metastasis of tumor cells.
Has been demonstrated that CPO not only inhibites the constitutive activation of PI3K/AKT/mTOR/S6K1 signaling cascade but also causes the activation of ERK, JNK, and p38 MAPK in tumor cells.
CPO induces increased reactive oxygen species ( ROS ) generation from mitochondria, which is associated with the induction of apoptosis, loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-3, and cleavage of PARP.
CPO also increases the expression of p53 and p21 and significantly potentiates the apoptotic effects of various pharmacological PI3K/AKT inhibitors when employed in combination in tumor cells.
Overall, these findings suggest that CPO can interfere with multiple signaling cascades involved in tumorigenesis and used as a potential therapeutic candidate for both the prevention and treatment of cancer.
β-Caryophyllene oxide Inhibits Constitutive and Inducible STAT3 Signaling Pathway Through Induction of the SHP-1 Protein Tyrosine Phosphatase, 2013.
β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation, 2011.
ANTI-INFLAMMATORY ACTIVITY and ATHEROSCLEROSIS
Chronic inflammation plays an important role in the development of atherosclerosis: a progressive disease characterized by the accumulation of lipids and fibrous elements in the large arteries. This inflammation is the mechanism that the body responses to the interactions between modified lipoproteins, monocytes, macrophages, T-cells and arterial endothelial cells.
Two fractions of the O. vulgare leaves extract, oregano S1 and oregano S2, were isolated using supercritical fluid extraction with CO2 and their composition was determined by gas chromatography-mass spectrometry (GCMS).
S1 and S2 have been used to test anti-inflammatory effects on activated human THP-1 cells (Human THP-1 monocytes cell line).
For both fractions, the main compounds present were trans-sabinene hydrate (a), thymol (b) and carvacrol (c ).
Fractions toxicity was assessed using the mitochondrial-respiration-dependent 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction method for several concentrations during 24 and 48 h of incubation. Concentrations higher than 30 microg/mL of both supercritical S1 and S2 oregano fractions caused a reduction in cell viability in a dose-dependent manner.
Oxidized-LDLs (oxLDLs) activated THP-1 macrophages were used as cellular model of atherogenesis and the release/secretion of cytokines (TNT-alpha, IL-1beta, IL-6 and IL-10) and their respective mRNA expressions were quantified both in presence or absence of supercritical oregano extracts.
The results showed also a decrease in pro-inflammatory TNF-alpha, IL-1beta and IL-6 cytokines synthesis by these , as well as an increase in the production of anti-inflammatory cytokine IL-10.
These results may suggest an anti-inflammatory effect of oregano extracts and their compounds in a cellular model of atherosclerosis.
Supercritical fluid extraction of oregano (Origanum vulgare) essentials oils: anti-inflammatory properties based on cytokine response on THP-1 macrophages, 2010.
THE OTHER SIDE OF THE COIN
These researches and articles proved a lot of useful proprieties of Oregan, and the use of its extracts could be very interesting in the treatment of many pathologies.
However, evidence of adverse effects in vitro results from other studies.
The cytotoxic effects of two components of the oregano essential oils, carvacrol and thymol, and their mixture, on the intestinal cells line Caco-2 after 24 and 48h of exposure are shown in the article: Cytotoxicity and morphological effects induced by carvacrol and thymol on the human cell line Caco-2, 2014.
These compounds can be used as food additives as antibacterial factors and as components in the development of active packaging materials.
Therefore, further studies are needed in order to assess the toxicity on human and ensure its safety.
