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HU ‐446 and HU ‐465, Derivatives of the Non‐psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells
Author(s) -
Kozela Ewa,
Haj Christeene,
Hanuš Lumir,
Chourasia Mukesh,
Shurki Avital,
Juknat Ana,
Kaushansky Nathali,
Mechoulam Raphael,
Vogel Zvi
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12637
Subject(s) - cannabidiol , experimental autoimmune encephalomyelitis , myelin oligodendrocyte glycoprotein , cannabinoid receptor , cannabinoid receptor type 2 , chemistry , cannabinoid , neuroinflammation , receptor , pharmacology , multiple sclerosis , inflammation , microbiology and biotechnology , immunology , biology , biochemistry , medicine , agonist , cannabis , psychiatry
Cannabidiol ( CBD ), the non‐psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis ( EAE ) model of multiple sclerosis ( MS ). Here we have studied the anti‐inflammatory effects of newly synthesized derivatives of natural (−)‐ CBD ((−)‐8,9‐dihydro‐7‐hydroxy‐ CBD ; HU ‐446) and of synthetic (+)‐ CBD ((+)‐8,9‐dihydro‐7‐hydroxy‐ CBD ; HU ‐465) on activated myelin oligodendrocyte glycoprotein ( MOG )35‐55‐specific mouse encephalitogenic T cells ( T MOG ) driving EAE / MS ‐like pathologies. Binding assays followed by molecular modeling revealed that HU ‐446 has negligible affinity toward the cannabinoid CB 1 and CB 2 receptors while HU ‐465 binds to both CB 1 and CB 2 receptors at the high nanomolar concentrations ( K i = 76.7 ± 5.8 n m and 12.1 ± 2.3 n m , respectively). Both, HU ‐446 and HU ‐465, at 5 and 10 μ m (but not at 0.1 and 1 μ m ), inhibited the MOG 35‐55‐induced proliferation of autoreactive T MOG cells via CB 1/ CB 2 receptor independent mechanisms. Moreover, both HU ‐446 and HU ‐465, at 5 and 10 μ m , inhibited the release of IL ‐17, a key autoimmune cytokine, from MOG 35‐55‐stimulated T MOG cells. These results suggest that HU ‐446 and HU ‐465 have anti‐inflammatory potential in inflammatory and autoimmune diseases.