Caryophyllene (/ˌkærioʊˈfɪliːn/), more formally(−)-β-caryophyllene (BCP), is a natural bicyclicsesquiterpene that occurs widely in nature. Caryophyllene is notable for having acyclobutane ring, as well as atrans-double bond in a 9-membered ring, both rarities in nature.[3]
Caryophyllene can be produced synthetically,[4] but it is invariably obtained from natural sources because it is widespread. It is a constituent of manyessential oils, especially clove oil, the oil from the stems and flowers ofSyzygium aromaticum (cloves), the essential oil ofCannabis sativa,copaiba,rosemary, andhops.[3] It is usually found as a mixture withisocaryophyllene (thecis double bond isomer) andα-humulene (obsolete name: α-caryophyllene), a ring-opened isomer.
Caryophyllene is one of the chemical compounds that contributes to thearoma ofblack pepper.[5]
β-Caryophyllene is underbasic research for its potential action as an agonist of thecannabinoid receptor type 2 (CB2 receptor).[6] In other basic studies, β-caryophyllene has a binding affinity of Ki = 155 nM at the CB2 receptors.[7]
β-Caryophyllene has the highest cannabinoid activity compared to the ring opened isomer α-caryophyllenehumulene which may modulate CB2 activity.[8] To compare binding,cannabinol binds to the CB2 receptors as a partial agonist with an affinity of Ki = 126.4 nM,[9] while delta-9-tetrahydrocannabinol binds to the CB2 receptors as a partial agonist with an affinity of Ki = 36 nM.[10]
Caryophyllene has been givengenerally recognized as safe (GRAS) designation by the FDA and is approved by the FDA for use as a food additive, typically for flavoring.[11][12] Rats given up to 700 mg/kg daily for 90 days did not produce any significant toxic effects.[13] Caryophyllene has anLD50 of 5,000 mg/kg in mice.[14][15]
14-Hydroxycaryophyllene oxide (C15H24O2) was isolated from the urine ofrabbits treated with (−)-caryophyllene (C15H24). TheX-raycrystal structure of 14-hydroxycaryophyllene (as itsacetate derivative) has been reported.[16]
Themetabolism of caryophyllene progresses through (−)-caryophyllene oxide (C15H24O) since the latter compound also afforded 14-hydroxycaryophyllene (C15H24O) as ametabolite.[17]
Caryophyllene oxide,[18] in which thealkene group of caryophyllene has become anepoxide, is the component responsible for cannabis identification bydrug-sniffing dogs[19][20] and is also an approved food additive, often as flavoring.[12] Caryophyllene oxide may have negligible cannabinoid activity.[21]
^Corey, E. J.; Mitra, R. B.; Uda, H. (1964). "Total Synthesis ofd,l-Caryophyllene andd,l-Isocaryophyllene".Journal of the American Chemical Society.86 (3):485–492.Bibcode:1964JAChS..86..485C.doi:10.1021/ja01057a040.
^abJirovetz, L.; Buchbauer, G.; Ngassoum, M. B.; Geissler, M. (November 2002). "Aroma compound analysis ofPiper nigrum andPiper guineense essential oils from Cameroon using solid-phase microextraction–gas chromatography, solid-phase microextraction–gas chromatography–mass spectrometry and olfactometry".Journal of Chromatography A.976 (1–2):265–275.doi:10.1016/S0021-9673(02)00376-X.PMID12462618.
• Asakawa, Y.; Taira, Z.; Takemoto, T.; Ishida, T.; Kido, M.; Ichikawa, Y. (June 1981). "X-Ray Crystal Structure Analysis of 14-Hydroxycaryophyllene Oxide, a New Metabolite of (—)-Caryophyllene, in Rabbits".Journal of Pharmaceutical Sciences.70 (6):710–711.Bibcode:1981JPhmS..70..710A.doi:10.1002/jps.2600700642.PMID7252830.S2CID38358882.
^Yang, Depo; Michel, Laura; Chaumont, Jean-Pierre; Millet-Clerc, Joëlle (1999). "Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis".Mycopathologia.148 (2):79–82.doi:10.1023/a:1007178924408.PMID11189747.S2CID24242933.
^Stahl, E.; Kunde, R. (1973). "Die Leitsubstanzen der Haschisch-Suchhunde" [The tracing substances of hashish search dogs].Kriminalistik (in German).27:385–389.
^Singh, G.; Marimuthu, P.; De Heluani, C. S.; Catalan, C. A. (January 2006). "Antioxidant and biocidal activities ofCarum nigrum (seed) essential oil, oleoresin, and their selected components".Journal of Agricultural and Food Chemistry.54 (1):174–181.Bibcode:2006JAFC...54..174S.doi:10.1021/jf0518610.hdl:11336/99544.PMID16390196.
^Zheljazkov, V. D.; Cantrell, C. L.; Tekwani, B.; Khan, S. I. (January 2008). "Content, composition, and bioactivity of the essential oils of three basil genotypes as a function of harvesting".Journal of Agricultural and Food Chemistry.56 (2):380–5.Bibcode:2008JAFC...56..380Z.doi:10.1021/jf0725629.PMID18095647.
^Calvo Irabién, L. M.; Yam-Puc, J. A.; Dzib, G.; Escalante Erosa, F.; Peña Rodríguez, L. M. (July 2009). "Effect of postharvest drying on the composition of Mexican oregano (Lippia graveolens) essential oil".Journal of Herbs, Spices & Medicinal Plants.15 (3):281–287.doi:10.1080/10496470903379001.S2CID86208062.
^Umezu, T.; Nagano, K.; Ito, H.; Kosakai, K.; Sakaniwa, M.; Morita, M. (December 2006). "Anticonflict effects of lavender oil and identification of its active constituents".Pharmacology Biochemistry and Behavior.85 (4):713–721.doi:10.1016/j.pbb.2006.10.026.PMID17173962.S2CID21779233.
^Kaul, Pran N; Bhattacharya, Arun K; Rajeswara Rao, Bhaskaruni R; Syamasundar, Kodakandla V; Ramesh, Srinivasaiyer (1 January 2003). "Volatile constituents of essential oils isolated from different parts of cinnamon (Cinnamomum zeylanicum Blume)".Journal of the Science of Food and Agriculture.83 (1):53–55.Bibcode:2003JSFA...83...53K.doi:10.1002/jsfa.1277.
