Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.
A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-kappaB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs). HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-kappaB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs. Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment. Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.
Rajesh
Mohanraj
M
Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institutes of Health/NIAAA, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413, USA
Mukhopadhyay
Partha
P
Bátkai
Sándor
S
Haskó
György
G
Liaudet
Lucas
L
Drel
Viktor R
VR
Obrosova
Irina G
IG
Pacher
Pál
P
D002185:Cannabidiol / Q000008:administration & dosage*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators; D002185:Cannabidiol; D005947:Glucose