Beta-caryophyllene protects against diet-induced dyslipidemia and vascular inflammation in rats: Involvement of CB2 and PPAR-γ receptors

• Published in: Chemico-biological interactions 2019-01, Vol.297, p.16-24
• Main Authors: Youssef, Dareen A., El-Fayoumi, Hassan M., Mahmoud, Mona F.
• Format: Article
• Language: English
• Subjects: Beta-caryophyllene; Cannabinoid receptor 2; High fat/fructose diet; Insulin resistance; PPAR-γ; Vascular inflammation
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2018.10.010

Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-α (PPAR-α). However, few studies reported the contribution of PPAR-γ receptors in BCP effects. The aim of this study was to investigate the BCP effects on diet-induced dyslipidemia and vascular inflammation as well as the involvement of CB2R and PPAR-γ receptors. Wistar rats were fed a high-fat diet and administered 10% fructose for 12 weeks. Treatment with pioglitazone, BCP, BCP + CB2R antagonist, AM630, or BCP + PPAR-γ antagonist, BADGE was started from the 9th week and continued till the 12th week. BCP significantly ameliorated all diet-induced alterations in a CB2R-dependant manner as it improved glycemic parameters, dyslipidemia, and vascular oxidative stress and inflammation. It also downregulated proatherogenic adhesion molecule (VCAM-1) and restored vascular eNOS/iNOS expression balance. PPAR-γ was involved in BCP-evoked suppression of vascular inflammation, VCAM-1 and restoration of normal vascular eNOS/iNOS balance thus normal NO level. Furthermore, part of BCP hypolipidemic effects (lowering total cholesterol, LDL, VLDL) involved both CB2R and PPAR-γ receptors. BCP treatment was superior to pioglitazone in anti-inflammatory and anti-atherosclerotic measures. BCP may represent a more potent alternate to pioglitazone avoiding its side effects in the treatment of insulin resistance and vascular inflammation. [Display omitted] •BCP modulates diet-induced dyslipidemia and insulin resistance.•BCP increases antioxidant potential and elevate HDL via CB2 receptors.•BCP mitigates vascular inflammation via both CB2 and PPAR-γ receptors.•BCP normalizes aortic NO level by increasing eNOS while decreasing iNOS expression.•BCP improves diet-induced aortic histopathological alterations.