目的:内源性大麻素系统(ECS)参与调节体内多种生理活动,比如新陈代谢和能量吸收,大麻素受体2(CNR2)是主要分布在外周的这些受体之一。β-石竹烯(BCP)是CNR2的激动剂,已知其具有药理活性,例如抗炎和抗氧化特性。在这项研究中,我们想研究BCP对肥胖小鼠是否具有药理作用及其机制。
方法:反向摄食节奏,丙基硫氧嘧啶腹膜内给药,BCP每天一次,连续四周,建立高脂血症肥胖小鼠模型。葡萄糖耐量试验,血脂水平测量,肝脏,腹膜,去除皮下脂肪,肝脏HE和油红O染色,用抗CNR2抗体进行免疫组织化学(IHC)染色。使用GO和KEGG数据库等工具检查肝脏的差异表达基因和与药物有效性相关的信号通路。
结果:BCP对减肥和改善血脂异常有显著作用。更重要的是,它显著降低了体内脂肪百分比,改善脂肪变性和肝细胞膨胀,减少脂肪积累,同时抑制腹周脂肪细胞的增殖。BCP可能通过昼夜节律调节和胆固醇代谢途径发挥其改善血脂异常和减轻体重的作用。最后,其改善血脂异常和降低体重的功效可能主要通过激活CNR2、激活SIRT1/PGC-1α/PPARγ和SIRT1/AMPK通路。
结论:BCP激活CNR2、SIRT1/PGC-1α/PPARγ信号通路,和SIRT1/AMPK信号通路发挥改善血脂异常和减轻体重的作用。
OBJECTIVE: The endogenous cannabinoid system (ECS) is involved in the regulation of a variety of physiological activities in the body, such as metabolism and energy uptake, and cannabinoid receptor 2 (CNR2) is one of these receptors that is predominantly distributed in the periphery. β-caryophyllene (BCP) is an agonist of CNR2 which is known to possess pharmacological activities such as anti-inflammatory and antioxidant properties. In this study, we wanted to investigate whether BCP possesses pharmacological effects on obese mice and its mechanism.
METHODS: Reversed feeding rhythm, propylthiouracil was delivered intraperitoneally, and BCP was gavaged once daily for four weeks to establish a hyperlipidemic obese mouse model. A glucose tolerance test, lipid level measurements, liver, peritoneal, and subcutaneous fat removal, HE and Oil Red O staining of the liver, and immunohistochemistry (IHC) staining with an anti-CNR2 antibody were all carried out. The liver was examined using tools like GO and KEGG databases for differentially expressed genes and signaling pathways linked to medication effectiveness.
RESULTS: BCP had significant effects on weight reduction and improvement of dyslipidemia. What\'s more, it significantly reduced body fat percentage, improved steatosis and ballooning of liver cells, and reduced fat accumulation, while inhibiting the proliferation of peri-abdominal adipocytes. BCP exerted its effects to improve dyslipidemia and reduce body weight probably through circadian regulation and cholesterol metabolic pathways. Finally, and its efficacy in improving dyslipidemia and reducing body weight may be mainly through activating CNR2, activating SIRT1/PGC-1α/PPARγ and SIRT1/AMPK pathways.
CONCLUSIONS: BCP activates the CNR2, SIRT1/PGC-1α/PPARγ signaling pathway, and SIRT1/AMPK signaling pathway to exert dyslipidemia-improving and weight-loss effects.