title: Protective effect of β-caryophyllene, a natural bicyclic sesquiterpene, against cerebral ischemic injury.
abstract: β-Caryophyllene (trans-4,11,11-trimethyl-8-methylenebicyclo[7,2,0]undec-4-ene), found in various plants, is a natural bicyclic sesquiterpene with a low toxicity. Here, we show that a single intraperitoneal injection of β-caryophyllene (10 mg/kg) significantly reduced the cortical infarct volume by 67% when given immediately before middle cerebral artery occlusion (MCAO). Neurological deficits caused by MCAO were also significantly decreased by β-caryophyllene. β-Caryophyllene treatment of cortical cells exposed to oxygen-glucose deprivation revealed a significant protection in a dose-dependent manner. However, β-caryophyllene neither suppressed N-methyl-D-aspartate excitotoxicity in cultured cortical cells nor markedly decreased the oxidative stress measured in the cellular or acellular systems. By contrast, treatments with β-caryophyllene dose-dependently inhibited mRNA expression of inducible nitric oxide synthetase, interleukin (IL)-1β, IL-6, and cyclooxygenase 2 in C6 microglial cells, and decreased the level of nitric oxide and prostaglandin E₂ at a 100 μM concentration. All of these findings suggest that β-caryophyllene has a potent neuroprotective activity, and its neuroprotection may be partly related to the modulation of inflammatory mediators.
authors.affiliation: Korea Food Research Institute, Sungnam, Kyonggi-do, Republic of Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Chang
authors.forename: Ji-Myung
authors.initials: JM
authors.lastname: Kim
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Chun
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D010944:Plants / Q000737:chemistry; D000081223:Polycyclic Sesquiterpenes; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D010936:Plant Extracts; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C024714:caryophyllene; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2