Protective Effect of beta-Caryophyllene, a Natural Bicyclic Sesquiterpene, Against Cerebral Ischemic Injury

Abstract

beta-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 beta-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 beta-caryophyllene. beta-Caryophyllene treatment of cortical cells exposed to oxygen-glucose deprivation revealed a significant protection in a dose-dependent manner. However, beta-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 bcaryophyllene dose-dependently inhibited mRNA expression of inducible nitric oxide synthetase, interleukin (IL)-1 beta, IL-6, and cyclooxygenase 2 in C6 microglial cells, and decreased the level of nitric oxide and prostaglandin E-2 at a 100 mu M concentration. All of these findings suggest that beta-caryophyllene has a potent neuroprotective activity, and its neuroprotection may be partly related to the modulation of inflammatory mediators.