caryophyllene and Atherosclerosis

Hypercholesterolemia and cardiac oxidative damage have been implicated in the pathophysiology of atherosclerosis. In earlier studies, treatment using natural phytocannabinoid β-caryophyllene caused a hypolipemic effect, as well as ameliorated hepatic oxidative damage. In this regard, the present study aimed to investigate whether β-caryophyllene treatment was able to protect the cardiac tissue against hypercholesterolemic atherosclerosis, and to investigate the involvement of antioxidant mechanisms in this effect using a model of hypercholesterolemia induced by Triton WR-1339. The hypercholesterolemic animals exhibited a significant increase in the cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) contents in cardiac tissue, as well as showed significant increase on atherogenic index (AI) and coronary risk index (CRI). Moreover, cardiac levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were increased in hypercholesterolemic animals, while the glutathione reduced (GSH) levels and glutathione peroxidase (GPx) activity were decreased. β-caryophyllene treatment reduced the cardiac lipid content, as well as decreased the AI and CRI. Moreover, the treatment was able to improve the antioxidant/oxidant status in heart tissue of hypercholesterolemic animals. In summary, β-caryophyllene possesses antioxidant properties, preventing lipidic oxidative damage and ameliorating the GPx activity, an important enzyme linked to the prevention of atherosclerosis. Thus, this compound can be used as an attempt to prevent or reduce atherosclerosis in hypercholesterolemic rats.

Topics: Animals; Atherosclerosis; Cholesterol; Coronary Disease; Disease Models, Animal; Female; Oxidative Stress; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Reactive Oxygen Species; Risk Factors; Sesquiterpenes

trans-Caryophyllene (TC) is a major component found in the essential oils of many spices and foods/medicinal plants. It is a natural sesquiterpene and has been the subject of numerous studies. However, the effects of TC on vascular inflammation remain unknown. In this study, we reported that TC treatment in human umbilical vein endothelial cells (HUVECs) prevented attachment of monocytic leukemia cell line THP-1 cells to endothelial cells. In addition, in vivo results indicate that TC inhibited macrophage infiltration to the aortic surface and reduced total serum levels of cholesterol and triglycerides. Importantly, administration of TC could inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1) both in vitro and in vivo. Notably, our data indicate that the inhibitory effects of TC on the expression of VCAM-1 are mediated by the JAK2/STAT1/IRF-1 pathway. TC is a specific agonist of the type 2 cannabinoid receptor (CB2R). Importantly, we further verified that the inhibitory effects of TC on the expression of IRF-1 and VCAM-1 are dependent on activation of CB2R. Inhibition of CB2R by either specific inhibitors or RNA interference abolished the inhibitory effects of TC on the expression of IRF-1 and VCAM-1. Our results suggest that TC might have a capacity to suppress the development of atherosclerosis.

Topics: Animals; Anti-Inflammatory Agents; Aorta; Aortic Diseases; Atherosclerosis; Cell Adhesion; Cell Line; Cholesterol; Coculture Techniques; Disease Models, Animal; Dose-Response Relationship, Drug; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Interferon Regulatory Factor-1; Janus Kinase 2; Leukocytes; Macrophages; Male; Mice, Inbred C57BL; Plaque, Atherosclerotic; Polycyclic Sesquiterpenes; Receptor, Cannabinoid, CB2; RNA Interference; Sesquiterpenes; Signal Transduction; STAT1 Transcription Factor; Transendothelial and Transepithelial Migration; Transfection; Triglycerides; Vascular Cell Adhesion Molecule-1