Carvacrol

Carvacrol[1]
IUPAC name 5-isopropyl-2-methylphenol[citation needed]
Identifiers
CAS number	499-75-2 Y
PubChem	10364
ChemSpider	21105867 Y
UNII	9B1J4V995Q Y
KEGG	C09840 Y
ChEMBL	CHEMBL281202 Y
Jmol-3D images	Image 1
SMILES Cc1ccc(cc1O)C(C)C
InChI InChI=1S/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4-7,11H,1-3H3 Y Key: RECUKUPTGUEGMW-UHFFFAOYSA-N Y InChI=1/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4-7,11H,1-3H3 Key: RECUKUPTGUEGMW-UHFFFAOYAI
Properties
Molecular formula	C10H14O
Molar mass	150.217 g/mol
Density	0.9772 g/cm3 at 20 °C
Melting point	1 °C, 274 K, 34 °F
Boiling point	237.7 °C, 511 K, 460 °F
Solubility in water	slightly soluble
Solubility	soluble in ethanol, diethyl ether, carbon tetrachloride, acetone[2]
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Carvacrol, or cymophenol, C₆H₃CH₃(OH)(C₃H₇), is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano and a pizza-like taste.^[3]

Natural occurrence

Carvacrol is present in the essential oil of Origanum vulgare, 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%. The Origanum species majorana and Dittany of Crete are rich in carvacrol, 50% resp. 60-80%.^[4]

Biological properties and use

Carvacrol inhibits the growth of several bacteria strains, e.g. Escherichia coli^[5] and Bacillus cereus. Its low toxicity together with its pleasant taste and smell suggests its use as a food additive to prevent bacterial contamination.^[6] In Pseudomonas aeruginosa it causes damages to the cell membrane of these bacteria and, unlike other terpenes, inhibits the proliferation of this germ.^[7] The cause of the antimicrobial properties is believed to be disruption of the bacteria membrane.^[8][9]
It is a potent activator of the human ion channels transient receptor potential V3 (TRPV3) and A1 (TRPA1).^[10] Application of carvacrol on the human tongue, as well as activation of TRPV3, causes a sensation of warmth. In addition carvacrol also activates, but rapidly desensitizes the pain receptor TRPA1 explaining its pungency.^[10]

It activates PPAR and suppresses COX-2 inflammation ^[11].

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.^[12]

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 which 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

• Origanum compactum ^{[13][clarification needed]}
• Origanum dictamnus ^{[14][clarification needed]}
• Origaum microphyllum ^{[15][clarification needed]}
• Origanum onites ^{[16], [17][clarification needed]}
• Origanum scabrum ^{[15][clarification needed]}
• Origanum vulgare ^{[18], [19][clarification needed]}
• Thymus glandulosus ^{[13][clarification needed]}

Toxicology

Carvacrol, like other essential oils, does not have many long-term genotoxic risks. The cytotoxic ability of carvacrol on prooxidant activity can make it an effective antiseptic and antimicrobial agent. ^{[20][clarification needed]} Carvacrol has been found to show antioxidant activity.

Antimicrobial activity:

• 25 different periodontopathic bacteria and strains^{[21][clarification needed]}
• Cladosporium herbarum ^{[21][clarification needed]}
• Penicillium glabrum^{[21][clarification needed]}
• Fungi such as F. moniliforme, R. solani, S. sclerotirum, and P. capisci^{[21][clarification needed]}

Compendial status

• British Pharmacopoeia ^[22]

See also

• Acceptable daily intake
• Thymol
• Essential Oils

Notes & references

•  This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed (1911). Encyclopædia Britannica (11th ed.). Cambridge University Press. 

1. ^ "Carvacrol data sheet from Sigma-Aldrich". http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/W224502. 
2. ^ Lide, David R. (1998). Handbook of Chemistry and Physics (87 ed.). Boca Raton, FL: CRC Press. pp. 3–346. ISBN 0-8493-0594-2 
3. ^ Ultee A, Slump RA, Steging G, Smid EJ (2000). "Antimicrobial activity of carvacrol toward Bacillus cereus on rice". J. Food Prot. 63 (5): 620–4. PMID 10826719. 
4. ^ De Vincenzi M, Stammati A, De Vincenzi A, Silano M (2004). "Constituents of aromatic plants: carvacrol". Fitoterapia 75 (7–8): 801–4. doi:10.1016/j.fitote.2004.05.002. PMID 15567271. 
5. ^ Du WX, Olsen CE, Avena-Bustillos RJ, McHugh TH, Levin CE, Friedman M (2008). "Storage Stability and Antibacterial Activity against Escherichia coli O157:H7 of Carvacrol in Edible Apple Films Made by Two Different Casting Methods". J. Agric. Food Chem. 56 (9): 3082–8. doi:10.1021/jf703629s. PMID 18366181. 
6. ^ Ultee A, Smid EJ (2001). "Influence of carvacrol on growth and toxin production by Bacillus cereus". Int. J. Food Microbiol. 64 (3): 373–8. doi:10.1016/S0168-1605(00)00480-3. PMID 11294360. 
7. ^ Cox SD, Markham JL (2007). "Susceptibility and intrinsic tolerance of Pseudomonas aeruginosa to selected plant volatile compounds". J. Appl. Microbiol. 103 (4): 930–6. doi:10.1111/j.1365-2672.2007.03353.x. PMID 17897196. 
8. ^ Di Pasqua R, Betts G, Hoskins N, Edwards M, Ercolini D, Mauriello G (2007). "Membrane toxicity of antimicrobial compounds from essential oils". J. Agric. Food Chem. 55 (12): 4863–70. doi:10.1021/jf0636465. PMID 17497876. 
9. ^ Cristani M, D'Arrigo M, Mandalari G, et al. (2007). "Interaction of four monoterpenes contained in essential oils with model membranes: implications for their antibacterial activity". J. Agric. Food Chem. 55 (15): 6300–8. doi:10.1021/jf070094x. PMID 17602646. 
10. ^ ^{a b} Xu H, Delling M, Jun JC, Clapham DE (2006). "Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels". Nat. Neurosci. 9 (5): 628–35. doi:10.1038/nn1692. PMID 16617338. 
11. ^ Hotta, M.; Nakata, R.; Katsukawa, M.; Hori, K.; Takahashi, S.; Inoue, H. (2010). "Carvacrol, a Component of Thyme Oil, Activates PPAR and Suppresses COX-2 Expression". Journal of Lipid Research, 51: 132–9. doi:10.1194/jlr.M900255-JLR200. 
12. ^ Austgulen LT, Solheim E, Scheline RR (1987). "Metabolism in rats of p-cymene derivatives: carvacrol and thymol". Pharmacol. Toxicol. 61 (2): 98–102. doi:10.1111/j.1600-0773.1987.tb01783.x. PMID 2959918. 
13. ^ ^{a b} Bouchra, Chebli et al.; Achouri, Mohamed; Idrissi Hassani, L.M; Hmamouchi, Mohamed (2003). "Chemical composition and antifungal activity of essential oils of seven Moroccan Labiatae against Botrytis cinerea Pers: Fr". Journal of Ethnopharmacology 89 (1): 165–169. doi:10.1016/S0378-8741(03)00275-7. PMID 14522450. 
14. ^ Liolios, C.C. et al.; Gortzi, O; Lalas, S; Tsaknis, J; Chinou, I (2009). "Liposomal incorporation of carvacrol and thymol isolated from the essential oil of Origanum dictamnus L. and in vitro antimicrobial activity". Food Chemistry 112 (1): 77–83. doi:10.1016/j.foodchem.2008.05.060. 
15. ^ ^{a b} Aligiannis, N. et al.; Kalpoutzakis, E.; Mitaku, Sofia; Chinou, Ioanna B. (2001). "Composition and Antimicrobial Activity of the Essential Oils of Two Origanum Species". J. Agric. Food Chem. 49 (9): 4168–4170. doi:10.1021/jf001494m. PMID 11559104. 
16. ^ Coskun, Sevki et al.; Girisgin, O; Kürkcüoglu, M; Malyer, H; Girisgin, AO; Kirimer, N; Baser, KH (2008). "Acaricidal efficacy of Origanum onites L. essential oil against Rhipicephalus turanicus (Ixodidae)". Parasitology Research 103 (2): 259–261. doi:10.1007/s00436-008-0956-x. PMID 18438729. 
17. ^ Ruberto, Giuseppe et al.; Biondi, Daniela; Meli, Rosa; Piattelli, Mario (2006). "Volatile flavour components of Sicilian Origanum onites L". Flavour and Fragrance Journal 8 (4): 197–200. doi:10.1002/ffj.2730080406. 
18. ^ Kanias, G. D. et al.; Souleles, C.; Loukis, A.; Philotheou-Panou, E. (1998). "Trace elements and essential oil composition in chemotypes of the aromatic plant Origanum vulgare". Journal of Radioanalytical and Nuclear Chemistry 227 (1 – 2): 23–31. doi:10.1007/BF02386426. 
19. ^ Figiel, Adam et al.; Szumny, Antoni; Gutiérrez-Ortíz, Antonio; Carbonell-Barrachina, ÁNgel A. (2010). "Composition of oregano essential oil (Origanum vulgare) as affected by drying method". Journal of Food Engineering 98 (2): 240–247. doi:10.1016/j.jfoodeng.2010.01.002. 
20. ^ Bakkali, F.; S. Averbeck, D. Averbeck, M. Idaomar (2007). "Biological effects of essential oils - A review". Food and Chemical Toxicology (Elsevier Ltd.) 46: 446–475. doi:10.1016/j.fet.2007.09.107. 
21. ^ ^{a b c d} American College of Toxicology, A (2006). "Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol". International Journal of Toxicology 25: 29–127. doi:10.1080/10915810600716653. PMID 16835130. 
22. ^ The British Pharmacopoeia Secretariat (2009). "Index, BP 2009". http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf. Retrieved 29 March 2010.