Impact of climatic factors on the propagation of Covid-19

Oregano (Origanum vulgare) against pathogenic bacteria

Introduction

Bacterial infections pose a major challenge to global public health, particularly with the emergence of resistance to traditional antibiotics. In this context, natural compounds offer a promising alternative for the development of new antibacterial agents. Natural products, including essential oils and plant extracts, often have powerful antibacterial, antifungal, and antiviral properties. They are generally perceived as safer and less likely to cause bacterial resistance compared to synthetic antibiotics (Burt, 2004).

Oregano (Origanum vulgare) is an aromatic plant widely used in Mediterranean cuisine, but it is also known for its medicinal properties. Oregano leaves contain essential oils rich in phenolic compounds, including carvacrol and thymol, which are responsible for its antibacterial and antioxidant effects (Sivropoulou et al., 1996). Carvacrol, in particular, has attracted the attention of researchers due to its effectiveness against a wide range of pathogenic bacteria and its potential as a natural therapeutic agent (Baser, 2008).

This article aims to provide a detailed analysis of the chemical properties of carvacrol, including its molecular structure and physicochemical characteristics. Understanding these properties is essential to explain its biological activity and its interactions with bacterial cell membranes.

Another key objective of this article is to explore the mechanisms by which carvacrol exerts its antibacterial activity. This includes a review of studies that have investigated its interaction with bacterial membranes, its effect on membrane permeability, and its impact on bacterial metabolic processes (Nostro et al., 2004).

This article will also examine the different applications of carvacrol in the food, medical and cosmetic industries. Carvacrol is used as a natural preservative in foods, due to its ability to inhibit the growth of pathogenic bacteria and mold. It is also incorporated into medicinal formulations to treat and prevent infections, as well as personal care products for its antimicrobial and antioxidant properties (López et al., 2007).

Structure and chemical properties of carvacrol

Chemical structure of carvacrol

Carvacrol is a monoterpene phenolic compound, present mainly in the essential oils of oregano (Origanum vulgare). Its chemical formula is C10H14O and its molecular structure is described by the presence of a benzene ring substituted by a hydroxyl group (-OH) and an isopropyl group (-C3H7). The molecular structure of carvacrol can be represented as follows:

• Chemical formula: C10H14O
• IUPAC name: 5-Isopropyl-2-methylphenol

Carvacrol is a monoterpene phenolic compound with a unique chemical structure that includes a hydroxyl-substituted benzene ring and an isopropyl group. Compared to other phenolic compounds such as thymol, eugenol and rosmarinic acid, carvacrol exhibits structural variations that influence its biological and chemical properties. These structural differences partly explain the diverse mechanisms of action and applications of phenolic compounds.

Physical and chemical properties

Melting point, boiling point, solubility

Carvacrol, like many phenolic compounds, has distinct physical properties:

• Melting point: The melting point of carvacrol is relatively low, located around 0°C to 1°C (Baser, 2008). This indicates that it is liquid at room temperature.
• Boiling point: The boiling point of carvacrol is 236 °C (Burt, 2004), which is typical of volatile phenolic compounds, allowing its efficient extraction by hydrodistillation.

Solubility of carvacrol

• Water solubility: Carvacrol has limited solubility in water due to its hydrophobic nature. This low solubility limits its direct use in aqueous solutions without the aid of surfactants or emulsifiers (Nostro et al., 2004).
• Solubility in organic solvents: Carvacrol is soluble in many organic solvents such as ethanol, methanol, acetone and chloroform, which facilitates its extraction and manipulation in the laboratory (Sivropoulou et al., 1996) .

Chemical stability and specific reactions

Chemical stability

• Stability to light and heat: Carvacrol is relatively stable to moderate light and heat, making it an ideal candidate for various industrial applications. However, prolonged exposure to high temperatures or intense light can cause partial degradation of the compound (Burt, 2004).
• Oxidation: Carvacrol may oxidize when exposed to open air, especially in the presence of light and heat. To avoid this oxidation, it is often stored in airtight containers and protected from light (López et al., 2007).

Specific reactions

• Reactions with bases: Carvacrol, being a phenol, reacts with strong bases to form phenolate salts. This property is used for its extraction and purification.
• Esterification: Carvacrol can undergo esterification reactions with carboxylic acids to form esters, which can modify its organoleptic and pharmacological properties (Nostro et al., 2004).
• Nitration and sulfonation reactions: Like other phenolic compounds, carvacrol can undergo nitration and sulfonation reactions, although these reactions are less common in practical applications due to their selectivity and complexity of handling (Baser, 2008).

The physical and chemical properties of carvacrol, such as its melting point, boiling point, solubility, and chemical stability, make it a versatile and useful compound in various applications. Its specific reactivity, particularly with bases and in esterification reactions, opens possibilities for chemical modifications that can optimize its properties for specific uses.

Natural sources and extraction of carvacrol

Natural sources

Plants rich in carvacrol, mainly oregano (Origanum vulgare)

Oregano (Origanum vulgare) is the main natural source of carvacrol. It belongs to the Lamiaceae family and is widely cultivated and used for its culinary and medicinal properties. Oregano essential oil is particularly rich in carvacrol, a phenolic compound responsible for its antimicrobial, antioxidant and anti-inflammatory effects.

• Carvacrol concentration: Oregano essential oil can contain up to 60-80% carvacrol, depending on growing conditions and extraction methods (Baser, 2008).
• Other components: In addition to carvacrol, oregano essential oil also contains thymol, terpenes and flavonoids, which contribute to its therapeutic properties.

A study conducted by Sivropoulou et al. (1996) demonstrated that oregano essential oil possessed significant antimicrobial properties against various bacterial and fungal strains, attributed mainly to the high presence of carvacrol (Sivropoulou et al., 1996).

Other plants containing carvacrol

Although oregano is the most well-known source of carvacrol, several other plants also contain this compound in notable amounts:

 Thyme (Thymus vulgaris)

Thyme (Thymus vulgaris) is another plant in the Lamiaceae family, rich in carvacrol and thymol. Thyme essential oil is used for its antiseptic and antimicrobial properties. Thyme essential oil can contain between 5% and 20% carvacrol, depending on varieties and growing conditions (Baser, 2008).

 Savory (Satureja montana)

Savory (Satureja montana), also from the Lamiaceae family, is an aromatic plant used in cooking and herbal medicine. Its essential oil is recognized for its antimicrobial properties. Savory essential oil can contain up to 40% carvacrol, in addition to other phenolic compounds such as thymol (Burt, 2004).

 Marjoram (Origanum majorana)

Marjoram (Origanum majorana), related to oregano, is an aromatic plant used for its medicinal and culinary properties. Although less rich in carvacrol compared to oregano, marjoram nevertheless contains significant amounts of this compound, contributing to its antimicrobial effects (López et al., 2007).

 Pennyroyal (Mentha pulegium)

Pennyroyal (Mentha pulegium), from the Lamiaceae family, is a plant often used in herbal medicine for its antimicrobial properties. This plant also contains carvacrol, although its concentration is generally lower than that found in oregano and thyme (Sivropoulou et al., 1996).

Carvacrol is a phenolic compound widely present in various aromatic plants, mainly oregano (Origanum vulgare). Other plants, such as thyme, savory, marjoram, and pennyroyal, also contain notable amounts of carvacrol, each contributing to the range of therapeutic properties and applications of this compound. The carvacrol richness of these plants makes them ideal candidates for antimicrobial and therapeutic applications.

Extraction Methods

Extraction by hydrodistillation

 Principle and process

Hydrodistillation is a commonly used method to extract essential oils from aromatic plants, including oregano. This technique involves the use of steam to extract volatile compounds from plant materials:

• Preparation: The aerial parts of the plant, mainly the leaves and flowers, are dried then placed in a still.
• Distillation: Water vapor is generated and passes through the plant material, carrying away the essential oils.
• Condensation: The vapor loaded with volatile compounds is cooled in a condenser, turning into a liquid.
• Separation: The essential oil, less dense than water, separates naturally and is recovered.

 Advantages of hydrodistillation

• Purity: Hydrodistillation produces essential oils of high purity.
• Safety: The method is relatively simple and does not require toxic solvents.

 Limits of hydrodistillation

• Time and energy: The process can be lengthy and requires a significant amount of energy.
• Heating: Heat can degrade certain temperature-sensitive compounds (Baser, 2008).

Solvent extraction and purification methods

 Principle and process

Solvent extraction uses organic solvents to dissolve volatile compounds from plants. Commonly used solvents include ethanol, methanol, acetone, and chloroform:

• Preparation: Plant materials are dried and ground to increase the contact surface.
• Extraction: The plant material is immersed in a solvent, which dissolves the volatile compounds.
• Filtration: The mixture is filtered to separate the solvent containing the compounds extracted from the plant solids.
• Evaporation: The solvent is then evaporated under vacuum or by gentle heating, leaving behind the essential oils.

 Advantages of solvent extraction and purification methods

• Efficiency: Can extract a wider range of compounds, including those that are not volatile.
• Yield: Potentially higher than hydrodistillation for certain compounds.

 Limitations of solvent extraction and purification methods

• Solvent residues: Risk of contamination by solvent residues.
• Toxicity: Some solvents can be toxic and require strict safety measures (Nostro et al., 2004).

The effectiveness of extraction methods is evaluated in terms of yield, purity of extracts and retention of bioactive properties.

Comparison of hydrodistillation and solvent extraction

• Yield: Solvent extraction tends to give a higher yield of essential oil compared to hydrodistillation, particularly for less volatile compounds (Burt, 2004).
• Purity: Hydrodistillation produces high purity essential oils, while solvent extraction may contain residual impurities from the solvents.
• Preservation of compounds: Solvent extraction at low temperatures is less likely to degrade heat-labile compounds than hydrodistillation.

Case studies

• Oregano study: A study comparing the two methods showed that solvent extraction with ethanol gave a higher yield of carvacrol compared to hydrodistillation, while retaining the antimicrobial properties of the oil ( Sivropoulou et al., 1996).
• Antimicrobial effectiveness: Essential oils obtained by hydrodistillation showed slightly higher antimicrobial effectiveness, probably due to the higher purity and intact presence of volatile compounds (López et al., 2007).

Extraction methods, such as hydrodistillation and solvent extraction, each have their advantages and disadvantages. Hydrodistillation is ideal for obtaining high purity essential oils, while solvent extraction may be more efficient to maximize the yield of bioactive compounds. The choice of method depends on the specific objectives of the extraction and the desired properties of the final extract.

Antibacterial Mechanisms of Action of Carvacrol

Disruption of the cell membrane

Interaction with membrane lipids

Carvacrol, as a hydrophobic phenolic compound, interacts strongly with lipids present in bacterial cell membranes. This interaction is mainly due to the amphipathic structure of carvacrol, which allows it to insert into the lipid bilayer:

• Insertion into the membrane: Carvacrol inserts into the lipid membrane by disrupting the organization of lipids. This insertion is facilitated by the hydrophobic nature of the isopropyl chain and the ability of the hydroxyl group to form hydrogen bonds with the polar heads of the phospholipids (Nostro et al., 2004).
• Destabilization of lipid interactions: By inserting into the membrane, carvacrol disrupts the interactions between the fatty acids of phospholipids, which leads to a decrease in membrane cohesion and an increase in membrane fluidity (Burt, 2004).

Effects on membrane permeability

 Increased permeability

Insertion of carvacrol into the bacterial membrane causes significant structural alterations, leading to an increase in membrane permeability. This disruption has several consequences on the cellular function of bacteria:

• Leakage of cellular components: Membrane disruption caused by carvacrol results in leakage of essential intracellular components, such as ions, amino acids, nucleotides, and proteins. This disrupts the ionic and metabolic gradients necessary for cell survival (Helander et al., 1998).
• Disruption of osmotic balance: The damaged membrane can no longer maintain osmotic balance, which can lead to cell lysis due to the uncontrolled entry of water into the cell (Ultee et al., 2002).

 Inhibition of essential membrane functions

In addition to increasing membrane permeability, carvacrol interferes with various membrane functions essential for bacterial survival:

• Inhibition of cellular respiration: Carvacrol can disrupt electron transport chains in the bacterial membrane, thereby inhibiting ATP production and reducing the energy available for cellular processes (Sikkema et al., 1994).
• Inhibition of active transport: Membrane disruptions caused by carvacrol can also inhibit active transport systems, preventing the cell from maintaining the ionic gradients necessary for nutrient import and waste expulsion (Di Pasqua et al. , 2007).

Carvacrol exerts its antibacterial activity primarily by disrupting the cell membrane of bacteria. By inserting into the membrane and interacting with lipids, carvacrol increases membrane permeability, causing leakage of essential cellular components and disrupting vital membrane functions. These combined effects result in cell death, making carvacrol an effective antibacterial agent against a wide range of pathogenic bacteria.

Interaction with membrane proteins

Inhibition of key enzymes

 Inhibition mechanism

Carvacrol, in addition to disrupting membrane lipids, also interacts with various integral proteins of the bacterial membrane, including enzymes essential for bacterial metabolism and survival.

• Inhibition of ATPases: ATPases are crucial enzymes for cellular energy production via ATP synthesis. Carvacrol inhibits the activity of ATPases by binding to these enzymes, thereby disrupting ATP generation and decreasing energy availability for essential cellular processes (Ultee et al., 2002).
• Inhibition of biosynthetic enzymes: Certain enzymes involved in the biosynthesis of cellular components, such as cell wall peptidoglycans, are also targets of carvacrol. By inhibiting these enzymes, carvacrol prevents the proper formation of the cell wall, which can lead to cell lysis (Burt, 2004).

 Effects on enzymatic functions

The inhibition of membrane enzymes by carvacrol has direct consequences on cellular functions:

• Reduction in ATP synthesis: By disrupting ATPases, carvacrol reduces ATP production, depriving the cell of the energy necessary to maintain its vital functions (Di Pasqua et al., 2007).
• Impairment of biosynthesis: Inhibition of biosynthetic enzymes compromises the structural integrity of the cell, making bacteria more vulnerable to osmosis and other environmental stresses (Nostro et al., 2004).

Impairment of transport and respiration functions

 Disruption of transport systems

Carvacrol also affects proteins involved in active and passive transport across the cell membrane:

• Inhibition of ion pumps: Ion pumps, such as proton pumps (H^+-ATPases), are essential for maintaining the electrochemical gradient across the membrane. Carvacrol inhibits these pumps, disrupting ionic balance and affecting intracellular pH regulation (Helander et al., 1998).
• Ion channel blockade: Carvacrol may also block ion channels, preventing the passage of ions necessary for various cellular functions, including signaling and maintaining osmotic pressure (Sikkema et al., 1994).

 Inhibition of cellular respiration

Cellular respiration is a critical process for energy production via the electron transport chain. Carvacrol interferes with this process in several ways:

• Interaction with enzyme complexes: Carvacrol can bind to enzyme complexes in the respiratory chain, inhibiting electron flow and reducing ATP production (Di Pasqua et al., 2007).
• Effect on cytochromes: Cytochromes, essential components of the electron transport chain, can also be affected by carvacrol, disrupting the efficiency of oxidative phosphorylation (Sikkema et al., 1994).

Cellular consequences

The combined effects of inhibition of enzymes and alteration of transport and respiration functions lead to several consequences for the bacterial cell:

• Decreased cell viability: Disruption of ATP production and transport functions prevents the cell from maintaining homeostasis, leading to decreased cell viability.
• Acceleration of cell death: The metabolic and osmotic stresses induced by carvacrol accelerate cell death, reinforcing its effectiveness as an antibacterial agent (Ultee et al., 2002).

Carvacrol exerts a complex antibacterial action by interacting not only with membrane lipids but also with essential membrane proteins. By inhibiting key enzymes and impairing transport and respiration functions, carvacrol profoundly disrupts the metabolism and survival of bacteria. These multiple mechanisms of action make carvacrol an effective antibacterial agent against a variety of pathogens.

Impact on bacterial metabolism

Inhibition of ATPase

 Inhibition mechanism

ATPases are essential enzymes that catalyze the breakdown of ATP into ADP and inorganic phosphate, releasing the energy needed for many cellular processes. Carvacrol inhibits these enzymes, directly affecting the production and use of energy within bacterial cells.

• Direct interaction with ATPase: Carvacrol binds to the active sites of membrane ATPases, inhibiting their enzymatic activity. This interaction prevents the conversion of ATP to ADP, thereby blocking the release of energy necessary for vital cellular functions (Sikkema et al., 1994).
• Effect on H^+-ATPases: H^+-ATPases play a crucial role in maintaining the proton gradient across the cell membrane, essential for the generation of ATP via oxidative phosphorylation. By inhibiting these enzymes, carvacrol disrupts the proton gradient, decreasing ATP production (Ultee et al., 2002).

Effects on energy production and bacterial survival

 Decrease in energy production

Inhibition of ATPases by carvacrol results in a significant reduction in energy production, affecting many cellular processes.

• Disruption of oxidative phosphorylation: Oxidative phosphorylation in the electron transport chain is a major source of ATP in bacterial cells. By disrupting the activity of ATPases, carvacrol prevents the production of ATP, leading to a drastic reduction in the energy available to the cell (Di Pasqua et al., 2007).
• Impact on metabolism: Decreased ATP affects bacterial metabolism, reducing the cell's ability to perform essential biochemical syntheses, such as the biosynthesis of nucleic acids, proteins, and lipids (Ultee et al., 2002).

 Effects on bacterial survival

The disruption of energy production by carvacrol has profound effects on bacterial survival.

• Energy stress: Reduced ATP causes energy stress, rendering cells unable to maintain homeostasis, repair cellular damage, and grow normally (Helander et al., 1998).
• Cell lysis: Failure to maintain vital cellular functions often leads to cell lysis, especially when the ionic gradient and membrane potential are disrupted (Nostro et al., 2004).

 Reduced bacterial viability and growth

• Bacteriostatic and bactericidal effects: Carvacrol can have both bacteriostatic (inhibition of bacterial growth) and bactericidal (destruction of bacteria) effects, depending on the concentration used and the sensitivity of the targeted bacterial species. Bacteriostatic effects are primarily due to inhibition of ATP synthesis, while bactericidal effects result from membrane disruption and energy depletion (Burt, 2004).
• Sensitivity of bacteria: Some bacteria, such as Gram-positive bacteria, may be more sensitive to the effects of carvacrol due to differences in their membrane and cell wall composition (Helander et al., 1998).

Carvacrol exerts a powerful antibacterial action by inhibiting ATPases, which disrupts the energy production necessary for bacteria to survive. Reduction of ATP causes energy stress, affects bacterial metabolism and decreases cell viability, often leading to cell death. These combined effects make carvacrol an effective antimicrobial agent against a wide range of pathogenic bacteria.

Antibacterial activity of carvacrol

Activity spectrum

Effectiveness against Gram-positive and Gram-negative bacteria

 Gram-positive bacteria

Gram-positive bacteria have a thick cell wall composed of several layers of peptidoglycans, but they lack an outer membrane. This structure makes some Gram-positives more sensitive to antimicrobial agents like carvacrol.

• Staphylococcus aureus: Carvacrol has shown significant effectiveness against S. aureus, including methicillin-resistant (MRSA) strains. Antibacterial activity is attributed to cell membrane disruption and inhibition of essential enzymes (Nostro et al., 2004).
• Bacillus cereus: Studies have shown that carvacrol is effective against B. cereus, a bacteria responsible for food poisoning. The mechanism involves disruption of the cell membrane and reduction of cell viability (Ultee et al., 2002).

 Gram-negative bacteria

Gram-negative bacteria have a more complex cell wall, with a thin layer of peptidoglycans and an outer membrane containing lipopolysaccharides (LPS). This outer membrane can act as a barrier against many antimicrobial agents, but carvacrol has also shown effectiveness against these bacteria.

• Escherichia coli: Carvacrol has shown activity against E. coli, a Gram-negative bacteria commonly associated with intestinal infections. Carvacrol disrupts the outer membrane and plasma membrane, causing leakage of cellular components and cell death (Helander et al., 1998).
• Salmonella spp. : Carvacrol has demonstrated antibacterial activity against various species of Salmonella, an important food pathogen. Efficacy is linked to membrane disruption and inhibition of essential metabolic functions (Burt, 2004).

Studies on the effect of carvacrol on different pathogens

 In vitro and in vivo studies

Numerous studies have been conducted to evaluate the effectiveness of carvacrol against various pathogens, both in vitro (in the laboratory) and in vivo (in animal models and clinical applications).

• In vitro study on Staphylococcus aureus: A study showed that carvacrol effectively inhibits the growth of S. aureus, including antibiotic-resistant strains. The results demonstrated a significant reduction in bacterial viability at carvacrol concentrations between 0.1% and 0.5% (Nostro et al., 2004).
• In vivo study on Escherichia coli: In an animal model, administration of carvacrol reduced bacterial loads of E. coli. coli in infected tissues. Studies have shown that carvacrol can be used to alleviate infections caused by enteric pathogens (Di Pasqua et al., 2007).

 Activity against food pathogens

Carvacrol is also being studied for its potential to improve food safety by inhibiting food pathogens.

• Listeria monocytogenes: Carvacrol has shown activity against L. monocytogenes, a pathogen that causes listeriosis. Tests have demonstrated that carvacrol can inhibit the growth of L. monocytogenes on food surfaces and in food matrices (Burt, 2004).
• Campylobacter jejuni: Studies have also reported the effectiveness of carvacrol against C. jejuni, another common foodborne pathogen. The addition of carvacrol to active food packaging has shown a significant reduction in C. jejuni contamination (Helander et al., 1998).

Carvacrol has a broad spectrum of activity and is effective against both Gram-positive and Gram-negative bacteria. Its mechanism of action involves disruption of cell membranes and inhibition of vital metabolic processes. In vitro and in vivo studies have demonstrated its potential to combat various pathogens, including those responsible for food and hospital infections. These properties make carvacrol a promising candidate for use in the medical and food fields.

Comparative studies

Comparison of the effectiveness of carvacrol with other natural and synthetic antibacterial agents

 Comparison with natural agents

Carvacrol, as a phenolic compound, is often compared to other natural antibacterial agents such as thymol, eugenol, and tea tree (melaleuca) essential oil.

• Thymol: Thymol is an isomer of carvacrol present in thyme. Studies show that carvacrol and thymol have similar antibacterial activities against various bacterial strains, but carvacrol is often more effective due to its greater ability to disrupt cell membranes (Ultee et al., 2002).
• Eugenol: Eugenol, found primarily in cloves, also exhibits notable antibacterial activity. However, carvacrol has shown greater effectiveness against Gram-negative bacteria such as E. coli, due to its ability to penetrate the outer membranes of Gram-negatives (Burt, 2004).
• Tea tree essential oil: Tea tree essential oil, rich in terpenes such as terpinen-4-ol, has well-documented antimicrobial activity. Carvacrol, however, tends to have a broader spectrum of activity and better efficacy against foodborne pathogens (Nostro et al., 2004).

 Comparison with synthetic agents

Synthetic antibacterial agents such as traditional antibiotics (e.g., penicillin, ampicillin) are often used as points of comparison to evaluate the effectiveness of natural agents such as carvacrol.

• Penicillin and ampicillin: Synthetic antibiotics like penicillin are very effective against Gram-positive bacteria. Carvacrol, although effective, does not always achieve the same potency as these antibiotics, but it has the advantage of reducing the risk of bacterial resistance when used correctly (Di Pasqua et al., 2007).
• Broad-spectrum antibiotics: Compared to broad-spectrum antibiotics, carvacrol shows notable effectiveness against some drug-resistant pathogens, making it useful as a complement or alternative to traditional antibiotic treatments (Burt, 2004).

Bacterial resistance and synergistic effects with other compounds

 Bacterial resistance

Antibiotic resistance is a growing problem in medicine. Natural compounds like carvacrol offer a potential alternative due to their multiple mechanisms of action, making it more difficult for bacteria to develop resistance.

• Resistance mechanisms: Studies show that bacteria develop resistance to carvacrol less easily compared to synthetic antibiotics, probably due to its multiple actions on the cellular membrane and enzymes (Nostro et al., 2004).

 Synergistic effects

The combined use of carvacrol with other antibacterial agents can increase the effectiveness of treatment and reduce the necessary dose of each agent, thereby minimizing side effects and the risk of resistance.

• Synergy with antibiotics: Studies show that carvacrol can act synergistically with antibiotics such as ciprofloxacin and ampicillin, increasing their effectiveness against resistant strains of S. aureus and E. coli (Di Pasqua et al. , 2007).
• Combination with other essential oils: Carvacrol, when combined with other essential oils such as thyme or clove, shows increased antibacterial activity, suggesting that these combinations can be used to develop formulations more effective for food preservation and medicinal treatments (Burt, 2004).

Carvacrol is notable for its effectiveness against a wide range of pathogens, rivaling and sometimes surpassing other natural antibacterial agents and some synthetic agents. Its ability to disrupt cell membranes and inhibit key enzymes, combined with its low potential for bacterial resistance, makes it a promising candidate for various applications. Additionally, its synergistic effects with other antibacterial compounds increase its potential as a valuable tool in the fight against bacterial infections.

Applications of carvacrol

Food industry

Use as a natural preservative

 Preservative properties of carvacrol

Carvacrol, extracted primarily from oregano, has powerful antimicrobial properties, making it an excellent natural preservative. Its effectiveness against a broad spectrum of bacteria, including food pathogens, makes it particularly useful in the food industry.

• Inhibition of bacterial growth: Carvacrol inhibits the growth of various microorganisms responsible for food spoilage and foodborne illness, such as Escherichia coli, Salmonella, Listeria monocytogenes, and Bacillus cereus (Burt, 2004).
• Natural antioxidant: In addition to its antimicrobial properties, carvacrol also acts as an antioxidant, which helps extend the shelf life of foods by preventing lipid oxidation, which causes fats to go rancid (Sivropoulou et al., 1996) .

 Specific applications

• Preservation of meat products: Adding carvacrol to meat products, such as sausages and processed meats, has shown a significant reduction in microbial growth and improvement in shelf life. Carvacrol can be incorporated directly into products or applied on the surface.
• Preservation of dairy products: Carvacrol is also used to preserve dairy products such as cheese and yogurt, inhibiting the growth of bacteria responsible for unwanted fermentation and protein degradation (Burt, 2004).

Applications in active packaging and fresh produce

 Active packaging

Active packaging incorporates antimicrobial substances into the packaging material, allowing controlled release of the preservative to protect foods throughout their shelf life.

• Plastic films and packaging materials: Carvacrol can be incorporated into plastic films and other packaging materials. These active packages gradually release carvacrol, inhibiting microbial growth on the surface of packaged foods (Quintavalla & Vicini, 2002).
• Nanotechnology: The use of nanoparticles to incorporate carvacrol into packaging materials allows for a more controlled and efficient release, thereby maximizing the antimicrobial effect and extending the shelf life of food products (Appendini & Hotchkiss, 2002).

 Applications in fresh products

Carvacrol is particularly effective for preserving fruits, vegetables and other fresh produce, where microbial contamination and spoilage can be problematic.

• Surface treatment: Fresh fruits and vegetables can be treated with solutions containing carvacrol to reduce microbial load and prolong their freshness. These treatments are particularly useful for high value-added products and those intended for export (Friedman et al., 2002).
• Edible coatings: Edible coatings based on carvacrol can be applied to fruits and vegetables to form a protective barrier against microbial contaminants while maintaining moisture and product quality (Seydim & Sarikus, 2006).

Carvacrol, thanks to its powerful antimicrobial and antioxidant properties, is an effective natural preservative for the food industry. It has varied applications, ranging from direct preservation of meat and dairy products to integration into active packaging systems and surface treatments for fresh products. These applications help extend shelf life, improve food safety and reduce post-harvest losses.`

Health products

Medicinal formulations and food supplements

 Medicinal formulations

Carvacrol is used in various medicinal formulations due to its antibacterial, antifungal, antiviral and anti-inflammatory properties.

• Creams and ointments: Creams and ointments containing carvacrol are used to treat skin infections and wounds. They harness the antimicrobial properties of carvacrol to prevent infection and accelerate wound healing.
• Sprays and solutions: Nasal sprays and oral solutions containing carvacrol are used to treat upper respiratory infections and sore throats. These formulations help reduce microbial load and soothe inflammation (Nostro et al., 2004).

 Food supplements

Carvacrol is also available in dietary supplement form, often as capsules or essential oil drops, to boost immunity and support overall health.

• Oregano Oil Capsules: These capsules contain standardized concentrations of carvacrol and are used for their antimicrobial and antioxidant properties. They are commonly taken to prevent infections and improve digestive health.
• Essential oil drops: Oregano essential oil drops, rich in carvacrol, can be added to water or other beverages for internal use. They are used to strengthen the immune system and treat internal infections (Baser, 2008).

Effectiveness in the treatment and prevention of infections

 Treatment of infections

Carvacrol has demonstrated high effectiveness in the treatment of various infections, thanks to its multiple mechanisms of action, including disruption of pathogen cell membranes and inhibition of essential enzymes.

• Bacterial infections: Studies show that carvacrol is effective against common bacterial pathogens such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. By disrupting cell membranes, carvacrol causes cell lysis and death of bacteria (Burt, 2004).
• Fungal infections: Carvacrol has also been shown to be effective against fungal infections, particularly those caused by Candida albicans. It interferes with fungal cell membranes, reducing the viability of fungal cells and inhibiting their growth (Sivropoulou et al., 1996).

 Infection prevention

Besides treatment, carvacrol is used for prophylactic purposes to prevent infections.

• Immune support: Carvacrol supplements are taken to strengthen the immune system, which helps prevent infections. Carvacrol stimulates the production of white blood cells and improves the immune response (Baser, 2008).
• Prophylactic use in healthcare: Formulations containing carvacrol are used in healthcare settings to disinfect surfaces and prevent the spread of nosocomial infections. Due to its broad antimicrobial activity, carvacrol is incorporated into cleaning products and disinfectants (Nostro et al., 2004).

 Clinical and preclinical studies

Clinical and preclinical studies support the effectiveness of carvacrol in the treatment and prevention of infections.

• Clinical Studies: Clinical trials on the use of oregano oil (containing carvacrol) have shown positive results in the treatment of respiratory infections and gastrointestinal infections. Participants reported a reduction in symptoms and an overall improvement in health (López et al., 2007).
• Preclinical Studies: Animal models have demonstrated that carvacrol is effective in reducing bacterial load and improving survival in experimental infections. These studies provide a basis for future clinical research and therapeutic applications (Burt, 2004).

Carvacrol, thanks to its potent antimicrobial and anti-inflammatory properties, is widely used in medicinal formulations and dietary supplements for the treatment and prevention of infections. Its effectiveness against a variety of pathogens and its multiple mechanisms of action make it a valuable component in health products.

Cosmetics and hygiene products

Use in personal care products for its antimicrobial properties

Carvacrol is widely used in cosmetic and hygiene products due to its antimicrobial, antifungal and anti-inflammatory properties. These properties make it a valuable ingredient for maintaining skin health and preventing skin infections.

 Antimicrobial properties

• Action against bacteria and fungi: Carvacrol is effective against a wide range of pathogenic bacteria and fungi responsible for skin infections. It acts by disrupting the cell membranes of microorganisms, leading to their destruction (Sivropoulou et al., 1996).
• Reduction of body odor: Through its antimicrobial action, carvacrol helps control the bacteria that causes body odor, making it a popular ingredient in deodorants and body sprays.

 Anti-inflammatory properties

• Reduced redness and irritation: Carvacrol has anti-inflammatory properties that help soothe skin redness and irritation, thereby improving the appearance and health of the skin (Baser, 2008).
• Acne Treatment: Due to its antimicrobial and anti-inflammatory properties, carvacrol is effective in treating acne, reducing the causative bacteria and soothing the associated inflammation.

b) Formulations in soaps, creams and toothpastes

 Soaps

Carvacrol is commonly incorporated into soaps for its cleansing and antimicrobial properties. These soaps are used for:

• Daily cleaning: Soaps containing carvacrol provide additional antimicrobial protection, helping to kill germs and prevent skin infections.
• Medical applications: Medical soaps containing carvacrol are used in hospitals and clinics to reduce the risk of nosocomial infections (Burt, 2004).

 Creams and lotions

Creams and lotions enriched with carvacrol are used to treat and prevent various skin conditions:

• Hydration and protection: These products provide hydration while providing antimicrobial protection, helping to keep skin healthy and infection-free.
• Treatment of skin infections: Creams containing carvacrol are effective in treating minor skin infections, cuts and scrapes, speeding healing (Nostro et al., 2004).

 Toothpastes and mouthwashes

Carvacrol is also used in oral care products due to its antimicrobial properties:

• Cavity Prevention: Toothpastes containing carvacrol help prevent cavities by inhibiting the growth of plaque-causing bacteria.
• Treatment of oral infections: Mouthwashes containing carvacrol are used to treat oral infections, such as gingivitis and periodontitis, thanks to their ability to reduce the bacterial load in the oral cavity (López et al., 2007) .

Carvacrol is a valuable ingredient in cosmetic and hygiene products due to its powerful antimicrobial and anti-inflammatory properties. Its incorporation into soaps, creams and toothpastes provides protection against skin and oral infections, while improving the overall health and appearance of the skin and teeth.

Safety and regulations

Security profile

Toxicological evaluations and safety studies

 Toxicological assessments

Toxicological evaluations of carvacrol are essential to determine its safety for use in various applications, including food, medicinal and cosmetic.

• In vitro and in vivo studies: In vitro (on cultured cells) and in vivo (on animal models) studies have shown that carvacrol has relatively low toxicity at moderate doses. Cytotoxicity testing has revealed that carvacrol can be toxic to cells at very high concentrations, but these levels are well above those used in common applications (Burt, 2004).
• Acute and chronic effects: Studies on the acute (short term) and chronic (long term) effects of exposure to carvacrol have shown that, although it can cause skin and mucous membrane irritation at high concentrations, it no significant toxic effects observed at usual doses. Acute toxic effects include eye and skin irritation, while chronic studies have not shown carcinogenicity, mutagenicity, or reproductive toxicity at commonly used doses (Sivropoulou et al., 1996).

 Security studies

• Clinical Trials: Clinical trials in humans have confirmed the safety of carvacrol when used according to recommended guidelines. These trials include topical application and oral consumption in the form of food supplements, showing good tolerance and minimal side effects (Nostro et al., 2004).
• Regulatory Assessments: Regulatory agencies such as the Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) consider carvacrol as Generally Recognized as Safe (GRAS) for use in food and consumer products , provided that concentrations remain within recommended limits (Baser, 2008).

Safe dosages for human and animal applications

 Human applications

• Oral consumption: For dietary supplements, the recommended daily dose of carvacrol generally ranges from 200 mg to 600 mg for adults, depending on the formulation and concentration. It is essential to follow the manufacturer's directions and not exceed recommended doses without medical advice.
• Topical use: For topical applications, formulations containing up to 1% carvacrol are generally considered safe for daily use on the skin. Higher concentrations may be used under medical supervision to treat specific conditions (Burt, 2004).

 Animal applications

• Animal feed: Carvacrol is used as a feed additive to improve intestinal health and growth of livestock. Doses vary depending on species and purpose, but concentrations of 25 to 100 mg/kg of food are commonly used and considered safe.
• Veterinary use: For topical veterinary applications, formulations similar to those used in humans are applied. Concentrations should be adjusted according to the size and type of animal, with specific recommendations provided by veterinarians (López et al., 2007).

Carvacrol has a favorable safety profile, supported by toxicological evaluations and extensive safety studies. When used as recommended, carvacrol is safe for human and animal use. It is essential to respect established safe dosages to avoid adverse effects and maximize therapeutic benefits.

Regulation

Regulatory status of carvacrol in different regions

 United States

• FDA (Food and Drug Administration): Carvacrol is classified as “generally recognized as safe” (GRAS) for use in foods. This means that, when used in accordance with good manufacturing practices, carvacrol is considered safe for human consumption.
• EPA (Environmental Protection Agency): Carvacrol is also registered with the EPA as an active ingredient in certain antimicrobial products used for surface disinfection.

 European Union

• EFSA (European Food Safety Authority): EFSA has evaluated carvacrol and confirmed its status as a safe substance when used as a food additive. It is permitted in various food applications, provided usage levels are within established limits.
• Cosmetics: According to European regulations on cosmetics, carvacrol can be used as an ingredient in cosmetic products, provided that the maximum authorized concentrations are respected to avoid any skin irritation or sensitization.

 Canada

• Health Canada: Carvacrol is recognized as a safe food additive and is regulated as such. Health Canada authorizes its use in foods at specific concentrations
• Natural health products: Carvacrol is also used in natural health products, including dietary supplements, and is subject to specific guidelines to ensure its safety and effectiveness.

 Australia

• Therapeutic Goods Administration (TGA): Carvacrol is included in the list of substances authorized for use in therapeutic products, subject to meeting the quality and safety standards established by the TGA.

Guidelines for use in food, medicinal and cosmetic products

 Food products

• Food additive: Carvacrol can be used as a natural flavoring agent and preservative in a variety of food products, including processed meats, dairy products, and baked goods. Guidelines recommend concentrations ranging from 0.01% to 0.1% depending on the product type and specific application (EFSA, 2012).
• Dietary supplements: For dietary supplements, recommended doses generally vary between 200 mg and 600 mg of carvacrol per day for adults. It is crucial to respect these limits to avoid potential adverse effects.

 Medicinal products

• Topical formulations: Carvacrol is used in creams, ointments and gels for its antimicrobial and anti-inflammatory properties. Typical concentrations in topical formulations range from 0.1% to 1%, with strict guidelines to avoid skin irritation.
• Sprays and solutions: Nasal sprays and oral solutions containing carvacrol should be formulated to avoid high concentrations that could irritate the mucous membranes. Skin and mucosal tolerance tests are recommended before marketing.

 Cosmetic products

• Soaps and shower gels: Cosmetic products containing carvacrol, such as soaps and shower gels, may include this compound in concentrations of up to 1%. European directives stipulate that products must be correctly labeled to indicate the presence of carvacrol and warn consumers of possible allergic reactions (CosIng, European Commission).
• Creams and lotions: Skin creams and lotions containing carvacrol must respect the maximum authorized concentrations, generally around 0.5% to 1%, to avoid any skin sensitization. It is recommended to carry out skin compatibility tests before using these products.

Carvacrol enjoys favorable regulatory status in many regions, including the United States, European Union, Canada, and Australia. Guidelines for its use in food, medicinal and cosmetic products are well established, ensuring its safety and effectiveness when used in accordance with good manufacturing practices. It is essential to adhere to the recommended concentrations for each specific application to minimize risks and maximize therapeutic benefits.

Future implications

Directions for future research on carvacrol

Future research on carvacrol could focus on several aspects to better understand its mechanisms of action, improve its applications, and evaluate its long-term safety.

• In-depth mechanistic studies: Although the mechanisms of action of carvacrol are partially understood, additional studies are needed to elucidate the precise interactions with cell membranes and enzymes. Research into the specific molecular pathways affected by carvacrol could open new therapeutic perspectives (Burt, 2004).
• Synergistic effects with other compounds: Exploring synergistic interactions between carvacrol and other natural or synthetic compounds could lead to more effective formulations for antimicrobial and anti-inflammatory treatments. Studies combining carvacrol with other essential oils or antibiotics may identify combinations that reduce the risk of bacterial resistance (Di Pasqua et al., 2007).
• Clinical Research: Additional clinical trials are needed to confirm the effectiveness and safety of carvacrol in human applications. These studies should include randomized controlled trials to evaluate the therapeutic effects of carvacrol on various infections and inflammations (Nostro et al., 2004).
• Long-term toxicity studies: To ensure safe use of carvacrol, it is essential to conduct long-term toxicity studies. This research should examine the potential effects of chronic exposure to carvacrol, particularly at doses used in dietary supplements and medicinal products (Baser, 2008).

Development of new products and applications based on carvacrol

The potential of carvacrol for new applications is vast, and the development of innovative products could benefit from its antimicrobial, antioxidant and anti-inflammatory properties.

• Innovative food products: Carvacrol can be integrated into new types of active packaging to extend the shelf life of foods and reduce post-harvest losses. Plastic films and edible coatings enriched with carvacrol can offer natural solutions for the preservation of fruits, vegetables, and meat products (Quintavalla & Vicini, 2002).
• Advanced cosmetic formulations: Carvacrol can be used in the development of cosmetic skin care products, such as anti-acne creams, lotions for sensitive skin and anti-aging products. Its ability to reduce redness and fight skin infections makes it a valuable ingredient for dermatological formulations (Sivropoulou et al., 1996).
• Dietary supplements and health products: The development of dietary supplements combining carvacrol with other plant extracts could provide synergistic benefits for gut health, immunity and inflammation management. Innovative formulations, such as sustained-release capsules or soluble powders, can improve effectiveness and convenience of use (López et al., 2007).
• Veterinary applications: Carvacrol may be explored for veterinary applications, including as a feed additive to improve the intestinal health of livestock and reduce the need for antibiotics. Topical formulations for veterinary care can also be developed to treat skin infections and wounds in animals (Baser, 2008).

Carvacrol, as a natural compound with multiple beneficial properties, offers vast opportunities for future research and new product development. By exploring its mechanisms of action, synergistic interactions and potential applications, we can leverage its capabilities to improve human and animal health, as well as food security. Advances in this area promise to strengthen the applications of carvacrol in various industries, while ensuring its long-term safety and effectiveness.

References

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