title: β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 Mice through CB2 receptor activation and the PPARγ pathway.
abstract: OBJECTIVE
  The activation of cannabinoid receptor 2 (CB2) has the beneficial effect of reducing neuroinflammatory response in the treatment of Alzheimer's disease (AD) and is suggested to trigger the peroxisome proliferator-activated receptor-γ (PPARγ) pathway; agonists of both receptors improve AD. Recently, the plant metabolite β-caryophyllene was shown to selectively bind to CB2 receptor and act as a full agonist.
  
  
  METHODS
  In this study, we examined the anti-inflammatory effect of β-caryophyllene in a transgenic APP/PS1 AD model and analyzed whether this effect was mediated by CB2 and PPARγ.
  
  
  RESULTS
  β-Caryophyllene, given orally, prevented cognitive impairment in APP/PS1 mice, and this positive cognitive effect was associated with reduced β-amyloid burden in both the hippocampus and the cerebral cortex. Moreover, β-caryophyllene reduced astrogliosis and microglial activation as well as the levels of COX-2 protein and the mRNA levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the cerebral cortex. The use of the CB2 antagonist AM630 or the PPARγ antagonist GW9662 significantly reversed the protective effects of β-caryophyllene on APP/PS1 mice.
  
  
  CONCLUSIONS
  These results demonstrate that the anti-inflammatory effect of the sesquiterpene β-caryophyllene involves CB2 receptor activation and the PPARγ pathway and suggest β-caryophyllene as an attractive molecule for the development of new drugs with therapeutic potential for the treatment of AD.
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Chongqing, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dong
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D053764:Presenilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D047495:PPAR gamma; D000081223:Polycyclic Sesquiterpenes; D053764:Presenilin-1; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C024714:caryophyllene