Carvacrol

Wikiipedia

Carvacrol, or cymophenol, C6H3CH3(OH)(C3H7), is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano.

Carvacrol is present in the essential oil of Origanum vulgare (oregano), oil of thyme, oil obtained from pepperwort, and wild bergamot. The essential oil of Thyme subspecies contains between 5% and 75% of carvacrol, while Satureja (savory) subspecies have a content between 1% and 45%. Origanum majorana (marjoram) and Dittany of Crete are rich in carvacrol, 50% and 60-80% respectively.

It is also found in tequila.

Biological properties and use

Carvacrol inhibits the growth of several bacteria strains, e.g. Escherichia coli and Bacillus cereus. Its low toxicity together with its pleasant taste and smell suggests its use as a food additive to prevent bacterial contamination.In Pseudomonas aeruginosa it causes damages to the cell membrane of these bacteria and, unlike other terpenes, inhibits their proliferation.The cause of the antimicrobial properties is believed to be disruption of the bacteria membrane.

It is a potent activator of the human ion channels transient receptor potential V3 (TRPV3) and A1 (TRPA1). Application of carvacrol on the human tongue, as well as activation of TRPV3, causes a sensation of warmth. In addition, carvacrol also activates, but then rapidly desensitizes, the pain receptor TRPA1; this explains its pungency.

It activates PPAR and suppresses COX-2 inflammation. PPARs are master regulators of genes involved in glucose and lipid metabolism.

In rats, carvacrol is quickly metabolized and excreted. The main metabolic route is esterification of the phenolic group with sulfuric acid and glucuronic acid. A minor pathway is oxidation of the terminal methyl groups to primary alcohols. After 24 hours, only very small amounts of carvacrol or its metabolites could be found in urine, indicating an almost complete excretion within one day.

A study led by Supriya Bavadekar reports that carvacrol stimulates apoptosis in prostate cancer cells.

Synthesis and derivatives

Carvacrol may be synthetically prepared by the fusion of cymol sulfonic acid with caustic potash; by the action of nitrous acid on 1-methyl-2-amino-4-propyl benzene; by prolonged heating of five parts of camphor with one part of iodine; or by heating carvol with glacial phosphoric acid or by performing a dehydrogenation of carvone with a Pd/C catalyst. It is extracted from Origanum oil by means of a 50% potash solution. It is a thick oil that sets at 20 °C to a mass of crystals of melting point 0 °C, and boiling point 236–237 °C. Oxidation with ferric chloride converts it into dicarvacrol, whilst phosphorus pentachloride transforms it into chlorcymol.

List of the plants that contain the chemical

• Monarda didyma
• Nigella sativa
• Origanum compactum
• Origanum dictamnus
• Origanum microphyllum
• Origanum onites
• Origanum scabrum
• Origanum vulgare
• Thymus glandulosus
• Lavandula multifida

Toxicology

Carvacrol does not have many long-term genotoxic risks. The cytotoxic effect of carvacrol can make it an effective antiseptic and antimicrobial agent. Carvacrol has been found to show antioxidant activity.

Antimicrobial activity:

• 25 Different periodontopathic bacteria and strains
• Cladosporium herbarum
• Penicillium glabrum
• Fungi such as F. moniliforme, R. solani, S. sclerotirum, and P. capisci

Articles/Studies

• The bioactivity and toxicological actions of carvacrol

Antibacterial

Antimicrobial and antibiofilm activities of essential oils against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus. - EOs from, chemotypes thymol, and carvacrol, displayed the highest antibacterial activity againstO157:H7 (MIC= 0.9 and 0.3 mg/mL, respectively) and MRSA (MIC= 1.2 and 0.6 mg/mL, respectively). These compounds from EOs had also the highest antibiofilm activity (inhibition percentage>70.3%).

• Citrus fruit extracts with carvacrol and thymol eliminated 7-log acid-adapted *Escherichia coli* O157:H7, *Salmonella* typhimurium, and *Listeria monocytogenes*: A potential of effective natural antibacterial agents
• Enhancement in site-specific delivery of carvacrol against methicillin resistant Staphylococcus aureus induced skin infections.
• Efficacy of poly(lactic acid)/carvacrol electrospun membranes against Staphylococcus aureus and Candida albicans in single and mixed cultures
• Carvacrol, cinnamaldehyde, thymol, or oregano oil inhibit Clostridum prefringens in beef.
• Thymol and carvacrol are highly promising candidates for the development of effective and safe drugs in the fight against visceral leishmaniasis.
• * Virulence of Pseudomonas aeruginosa exposed to carvacrol: alterations of the Quorum sensing at enzymatic and gene levels.
• Carvacrol reduces Clostridium difficile sporulation and spore outgrowth in vitro
• Effects of Carvacrol on Survival, Mesenteric Blood Flow, Aortic Function and Multiple Organ Injury in a Murine Model of Polymicrobial Sepsis
• Evaluation of the antibacterial activity and efflux pump reversal of thymol and carvacrol against Staphylococcus aureus.
• Carvacrol enhances the antimicrobial potency of berberine in Bacillus subtilis.
• Carvacrol exhibited rapid bactericidal action against S. pyogenes.
• Antibacterial and antibiofilm activity of carvacrol against oral pathogenic bacteria.
• Antimicrobial activity of carvacrol and its derivatives on Mycobacterium.
• Inhibitory effects of Carvacrol on biofilm formation in Colistin Heteroresistant Acinetobacter baumannii clinical isolates.

Anti-inflammatory

• Carvacrol reduced inflammatory cytokine and chemokine while increased anti-inflammatory cytokines in veterans exposed to mustard gas.
• Anti-inflammatory and antioxidant activity of carvacrol in the respiratory system.

Antifungal

• Antifungal activity of thymol and carvacrol against postharvest pathogens Botrytis cinerea.
• Carvacrol derivatives as antifungal agents.

Antioxidant

• Natural compounds rosmarinic acid and carvacrol counteract aluminium-induced oxidative stress.

Bronchial Asthma

• Carvacrol may be a promising protective agent against bronchial asthma.

Cancer

• Carvacrol (found in oregano, savory, thymbra, thyme, corydothymus) is a potent inhibitor of cell growth in non-small cell carcinoma lines.
• Antitumor effects of carvacrol and thymol: A systematic review.
• Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2
• Both curcumin and carvacrol showed a great efficacy against hepatocellular carcinoma.
• The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2)
• In vitro pro-oxidant/antioxidant role of carvacrol, thymol and their mixture in the intestinal Caco-2 cell line
• Antiproliferative and anti-invasion effects of carvacrol on PC3 human prostate cancer cells.
• Dietary flavonoid carvacrol triggers the apoptosis of human breast cancer MCF-7 cells via the p53/Bax/Bcl-2 axis.
• Carvacrol treatment suppressed the growth of HPV-C33A cervical cancer cells.
• Carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve.

Cardiovascular

• Carvacrol has a hypotensive effect in normotensive rats.
• Carvacrol protects against diabetes-induced hypercontractility in the aorta through activation of the PI3K/Akt pathway.
• Anti-inflammatory activity of carvacrol protects the heart from lipopolysaccharide-induced cardiac dysfunction.
• Protective effects of carvacrol on lipid profiles, oxidative stress, hypertension, and cardiac dysfunction.

COVID-19

Would carvacrol be a supporting treatment option effective in minimizing the deleterious effects of COVID-19?

Diabetes

• Carvacrol is potential molecule for diabetes treatment.
• Carvacrol exerted an anti-hyperglycemic effect in streptozotocin-induced diabetes.
• Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus.

Gastroprotective

• Carvacrol and pomegranate decrease methotrexate related damage and apoptotic activity in intestinal tissue.

Hepatoprotective

• Carvacrol normalizes elevated liver enzymes induced by d-galactosamine-induced hepatotoxicity in rats.
• Carvacrol obtained from oregano oil significantly increases the liver regeneration rate in rats undergoing partial hepatectomy.
• Beneficial Effects of Carvacrol on In Vitro Models of metabolically-associated liver steatosis and endothelial dysfunction.
• Carvacrol protects rat liver exposed to formaldehyde by regulating oxidative stress, and asprosin and subfatin hormones.
• Carvacrol may be a promising protective agent in λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity.
• Carvacrol prevents acrylamide-induced oxidative and inflammatory liver damage and dysfunction.
• Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma.

Lungs

• Carvacrol can be used as a protective agent against benzo(a)pyrene-induced lung toxicity and inflammation.

Migraine

• Pharmacological evaluation of carvacrol anti-migraine potential.

Neuroprotective

• The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress.
• Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine
• Carvacrol has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.
• Carvacrol reduces hippocampal cell death and improves learning and memory deficits following lead-induced neurotoxicity via antioxidant activity.
• This study provided the evidence regarding the protective effects of carvacrol and thymol against Aβ25–35-induced cytotoxicity in PC12 cells.
• Carvacrol attenuated neuroinflammation, oxidative stress and depression and anxiety like behaviors.
• Neuroprotective potential and underlying pharmacological mechanism of carvacrol for Alzheimer's and Parkinson's diseases.
• Effect of carvacrol on histological analysis and expression of genes involved in an animal model of multiple sclerosis.
• Neuroprotective role of carvacrol in Parkinson's disease.
• Anti-cholinesterase and anti-α-amylase activities and neuroprotective effects of carvacrol.

Radiation Protection

Radioprotective effects of carvacrol and/or thymol against gamma irradiation-induced acute nephropathy.

Renoprotective

Carvacrol preserves antioxidant status and attenuates kidney fibrosis.

Other Effects

• Carvacrol and Zataria multiflora influenced the PPARγ agonist effects on systemic inflammation and oxidative stress induced by inhaled paraquat.
• Carvacrol promotes angiogenic paracrine potential and endothelial differentiation of human mesenchymal stem cells at low concentrations
• Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion.
• Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment.
• Carvacrol prodrugs with antimicrobial activity loaded on clay nanocomposites.
• Carvacrol reduces mercuric chloride-induced testicular toxicity.