title: (-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis.
abstract: (-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination. Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor. Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.
authors.affiliation: Laboratory of Autoimmunity and Immunopharmacology (LAIF), Department of Health Sciences, Center of Araranguá, Federal University of Santa Catarina, Araranguá 88906-072, Brazil. alberti.thais@gmail.com.
authors.forename: Thaís Barbosa
authors.initials: TB
authors.lastname: Alberti
authors.affiliation: Faculty of Pharmaceutical Sciences, Federal University of Pará, Belém 66075-740, Brazil. zweigw@gmail.com.
authors.forename: Wagner Luiz Ramos
authors.initials: WL
authors.lastname: Barbosa
authors.affiliation: Faculty of Pharmaceutical Sciences, Federal University of Pará, Belém 66075-740, Brazil. jvieira@ufpa.br.
authors.forename: José Luiz Fernandes
authors.initials: JL
authors.lastname: Vieira
authors.affiliation: Research and Innovation in Health Sciences (NUPICS), Federal University of Juiz de Fora, Juiz de Fora 36036-900, Brazil. nadiacritt@gmail.com.
authors.forename: Nádia Rezende Barbosa
authors.initials: NR
authors.lastname: Raposo
authors.affiliation: Laboratory of Autoimmunity and Immunopharmacology (LAIF), Department of Health Sciences, Center of Araranguá, Federal University of Santa Catarina, Araranguá 88906-072, Brazil. rafaelcdutra@gmail.com.
authors.forename: Rafael Cypriano
authors.initials: RC
authors.lastname: Dutra
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000517:prevention & control; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000517:prevention & control; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D020078:Neurogenic Inflammation / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010243:Paralysis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000081223:Polycyclic Sesquiterpenes; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D063386:Cannabinoid Receptor Agonists; D016207:Cytokines; D000081223:Polycyclic Sesquiterpenes; D043885:Receptor, Cannabinoid, CB2; D012717:Sesquiterpenes; C024714:caryophyllene
keywords: (−)-β-caryophyllene; CB2 receptor; experimental autoimmune encephalomyelitis; multiple sclerosis; neuroinflammation; phytocannabinoid