1.02020-03-18 23:23:57 UTC2020-12-07 19:07:04 UTCCDB000078beta-Caryophyllenebeta-Caryophyllene, also known as caryophyllene or (−)-β-caryophyllene, is a natural bicyclic sesquiterpene. It is usually found as a mixture with isocaryophyllene (the cis double bond isomer) and α-humulene (obsolete name: α-caryophyllene), a ring-opened isomer. beta-Caryophyllene is notable for having both a cyclobutane ring and a trans-double bond in a nine-membered ring, both rarities in nature. It is barely soluble in water and soluble in alcohol and propylene glycol. beta-Caryophyllene, a promising precursor for the production of high density fuels, has been biosynthesized in E.coli from the common terpene precursors dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). First, single units of DMAPP and IPP are reacted via a substitution, nucleophilic (SN)1-type reaction with the loss of pyrophosphate, catalyzed by the enzyme geranyl diphosphate synthetase (GPPS2), to form geranyl pyrophosphate (GPP). This further reacts with a second unit of IPP, also via an SN1-type reaction catalyzed by the enzyme farnesyl diphospahe synthetase (IspA), to form farnesyl pyrophosphate (FPP). Finally, FPP undergoes beta-caryophyllene synthase -catalyzed intramolecular cyclization to form caryophyllene (https://doi.org/10.1016%2Fj.renene.2016.06.061). It is an abundant constituent of many essential oils including that of Syzygium aromaticum (clove bud, up to 19%; ), Cannabis sativa flower (up to 37%; http://www.internationalhempassociation.org/jiha/jiha4208.html; PMID: 6991645), rosemary, and hops. beta-Caryophyllene is also found in cannabis smoke and is volatilized during the combustion of cannabis (https://doi.org/10.1007/978-1-59259-947-9_2). beta-Caryophyllene is a sweet and dry tasting compound that can be found in a number of food items such as allspice, fig, pot marjoram, and roman camomile, which makes beta-caryophyllene a potential biomarker for the consumption of these food products. beta-Caryophyllene can be found in feces and saliva. Beta-caryophyllene is a major sesquiterpene of various plant essential oils that reportedly has antioxidant, anti-inflammatory (PMID: 24484210), anticancer (PMID: 27696789), cardioprotective (PMID: 30343038), hepatoprotective, gastroprotective, nephroprotective, antimicrobial, immune-modulatory activity and neuroprotective effects. It has a role in alleviating pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer's disease and may mediates these effects through interactions with the cannabinoid receptors (CR), especially CBR2 (PMID: 30281175; PMID: 18574142).C15H24204.36204.1878(1S,4Z,9S)-4,11,11-trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene(1S,4Z,9S)-4,11,11-trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene87-44-5C\C1=C\CCC(=C)[C@H]2CC(C)(C)[C@H]2CC1InChI=1S/C15H24/c1-11-6-5-7-12(2)13-10-15(3,4)14(13)9-8-11/h6,13-14H,2,5,7-10H2,1,3-4H3/b11-6-/t13-,14+/m1/s1NPNUFJAVOOONJE-FGHOCRGKSA-N belongs to the class of organic compounds known as sesquiterpenoids. These are terpenes with three consecutive isoprene units.SesquiterpenoidsOrganic compoundsLipids and lipid-like moleculesPrenol lipidsSesquiterpenoidsAliphatic homopolycyclic compoundsBranched unsaturated hydrocarbonsCyclic olefinsPolycyclic hydrocarbonsUnsaturated aliphatic hydrocarbonsAliphatic homopolycyclic compoundBranched unsaturated hydrocarbonCaryophyllane sesquiterpenoidCyclic olefinHydrocarbonOlefinPolycyclic hydrocarbonSesquiterpenoidUnsaturated aliphatic hydrocarbonUnsaturated hydrocarbonlogp5.35logs-4.83logp4.52iupac(1S,4Z,9S)-4,11,11-trimethyl-8-methylidenebicyclo[7.2.0]undec-4-eneaverage_mass204.36mono_mass204.1878smilesC\C1=C\CCC(=C)[C@H]2CC(C)(C)[C@H]2CC1formulaC15H24inchiInChI=1S/C15H24/c1-11-6-5-7-12(2)13-10-15(3,4)14(13)9-8-11/h6,13-14H,2,5,7-10H2,1,3-4H3/b11-6-/t13-,14+/m1/s1inchikeyNPNUFJAVOOONJE-FGHOCRGKSA-Npolar_surface_area0refractivity67.45polarizability25.96rotatable_bond_count0acceptor_count0donor_count0physiological_charge0formal_charge0number_of_rings2bioavailability1rule_of_fiveYesghose_filterYesveber_ruleYesmddr_like_ruleYes5498518Turner CE, Elsohly MA, Boeren EG: Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod. 1980 Mar-Apr;43(2):169-234. doi: 10.1021/np50008a001.6991645Sain S, Naoghare PK, Devi SS, Daiwile A, Krishnamurthi K, Arrigo P, Chakrabarti T: Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells. Antiinflamm Antiallergy Agents Med Chem. 2014 Mar;13(1):45-55. doi: 10.2174/18715230113129990016.24484210Fidyt K, Fiedorowicz A, Strzadala L, Szumny A: beta-caryophyllene and beta-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Cancer Med. 2016 Oct;5(10):3007-3017. doi: 10.1002/cam4.816. Epub 2016 Sep 30.27696789Youssef DA, El-Fayoumi HM, Mahmoud MF: Beta-caryophyllene protects against diet-induced dyslipidemia and vascular inflammation in rats: Involvement of CB2 and PPAR-gamma receptors. Chem Biol Interact. 2019 Jan 5;297:16-24. doi: 10.1016/j.cbi.2018.10.010. Epub 2018 Oct 19.30343038Machado KDC, Islam MT, Ali ES, Rouf R, Uddin SJ, Dev S, Shilpi JA, Shill MC, Reza HM, Das AK, Shaw S, Mubarak MS, Mishra SK, Melo-Cavalcante AAC: A systematic review on the neuroprotective perspectives of beta-caryophyllene. Phytother Res. 2018 Dec;32(12):2376-2388. doi: 10.1002/ptr.6199. Epub 2018 Oct 3.30281175Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, Altmann KH, Karsak M, Zimmer A: Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9099-104. doi: 10.1073/pnas.0803601105. Epub 2008 Jun 23.18574142