Beta-caryophyllene protects against diet-induced dyslipidemia and vascular inflammation in rats: Involvement of CB2 and PPAR-γ receptors
Beta-caryophyllene protects against diet-induced dyslipidemia and vascular inflammation in rats: Involvement of CB2 and PPAR-γ receptors
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DOI：
10.1016/j.cbi.2018.10.010
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发表时间：
2019-01-05
影响因子：
5.1
通讯作者：
Mahmoud, Mona F.
中科院分区：
文献类型：
--
作者：
Youssef, Dareen A.;El-Fayoumi, Hassan M.;Mahmoud, Mona F.
β-香芹烯（BCP）是一种植物大麻素，对大麻素2型受体（CB 2 R）和过氧化物酶体增殖物激活受体-α（PPAR-alpha）具有选择性激动活性。然而，很少有研究报告的贡献，PPAR-gamma受体的BCP效应。本研究的目的是研究BCP对饮食诱导的血脂异常和血管炎症的影响以及CB 2 R和PPAR-gamma受体的参与。Wistar大鼠喂食高脂饮食，并给予10%果糖12周。从第9周开始给予吡格列酮、BCP、BCP + CB 2 R拮抗剂、AM 630或BCP + PPAR-gamma拮抗剂、BADGE治疗，并持续至第12周。BCP以CB 2 R依赖性方式显著改善了所有饮食诱导的改变，因为它改善了血糖参数、血脂异常、血管氧化应激和炎症。下调促动脉粥样硬化粘附分子（VCAM-1），恢复血管eNOS/iNOS表达平衡。PPAR-gamma参与BCP诱导的血管炎症、VCAM-1的抑制和正常血管eNOS/iNOS平衡的恢复，从而使NO水平正常。此外，BCP的部分降血脂作用（降低总胆固醇、LDL、VLDL）涉及CB 2 R和PPAR-gamma受体。BCP治疗在抗炎和抗动脉粥样硬化方面上级吡格列酮。BCP可能是吡格列酮的一种更有效的替代药物，可避免其在治疗胰岛素抵抗和血管炎症方面的副作用。
Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-alpha (PPAR-alpha). However, few studies reported the contribution of PPAR-gamma 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-gamma 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-gamma 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-gamma 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-gamma 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.