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Cannabidiol Attenuates Cardiac Dysfunction, Oxidative Stress, Fibrosis, Inflammatory and Cell Death Signaling Pathways in Diabetic Cardiomyopathy
Author(s) -
Mohanraj Rajesh,
Mukhopadhyay Partha,
Bátkai Sándor,
Patel Vivek,
Horváth Béla,
Wink David A,
Pacher Pal,
Mechoulam Raphael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.821.46
Cannabidiol (CBD), the most abundant non‐psychoactive constituent of Cannabis Sativa (marijuana) plant, exerts anti‐inflammatory effects in various disease models. Here, we have investigated the effects of cannabidiol (CBD) on myocardial dysfunction, inflammation, oxidative/nitrative stress, cell death and interrelated signaling pathways, using a mouse model of type I diabetic cardiomyopathy and primary human cardiomyocytes (HCM) exposed to high glucose (HG). Diabetic cardiomyopathy was characterized by declined diastolic and systolic myocardial performance associated with increased oxidative‐nitrative stress, NF‐κB and MAPK (JNK and p‐38, p38α)activation, enhanced expression of adhesion molecules (ICAM‐1, VCAM‐1), TNF‐α, markers of fibrosis (TGF‐β, CTGF, fibronectin, collagen‐1, MMP‐2 and MMP‐9), enhanced cell death (caspase 3/7 and PARP activity, chromatin fragmentation and TUNEL) and diminished Akt phosphorylation. Remarkably, CBD attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrosative stress, inflammation, cell death, and interrelated signaling pathways. Furthermore, CBD also attenuated the HG‐induced increased ROS generation, NF‐κB activation and cell death in HCM. Owing to excellent safety and tolerability of CBD in humans, our findings underscore its tremendous therapeutic potential for the treatment of diabetic cardiovascular complications. This work was supported by intramural funds from NIH/NIAAA.