Shi Jinghong, Yan Jianqun, Lei Qi, Zhao Junjie, Chen Ke, Yang Dejun, Zhao Xiaolin, Zhang Yuan
Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China.
Brain Res. 2009 Jan 9;1247:71-8. doi: 10.1016/j.brainres.2008.09.091. Epub 2008 Oct 15.
Evodiamine (Evo), an alkaloidal component extracted from the fruit of Evodiae fructus (Evodia rutaecarpa Bentham, Rutaceae), decreases the body weight of rats through a poorly defined mechanism. The hypothalamus is one of the areas in the brain linked to the control of food intake and energy expenditure. We postulate that Evo mediates this activity by modulating feeding-related peptides in the hypothalamus. We investigated the effects of Evo on food intake, body weight, the mRNA expression and peptide level of feeding-related peptides in the hypothalamus, in male rats. The juvenile rats of 5 weeks old were used at the start of the experiment. Evo (40 mg/kg or 4 mg/kg) was administered intragastrically for 25 days, and food intake and body weight of rats were recorded daily. Blood samples were collected for leptin radioimmunoassay (RIA). Real-Time PCR was used to analyze the mRNA expression. Western Blotting and immunohistochemistry were used to analyze the peptide. Our results show that intragastric administration of Evo (40 mg/kg) decreased rate of food intake and body weight increase following rat growth, reduced orexigenic neuropeptide Y (NPY) and agouti-gene related protein (AgRP) mRNA levels and NPY peptide level in the arcuate nucleus (ARC) of the hypothalamus, but it increases the circulating level of leptin. Intragastric administration of a smaller dose of Evo (4 mg/kg) was ineffective. These data suggest that Evo decreases food intake, and therefore body weight, partly by down-regulating NPY and AgRP mRNA expression and peptide expression in the ARC of the hypothalamus.
吴茱萸碱（Evo）是从吴茱萸（Evodia rutaecarpa Bentham，芸香科）果实中提取的一种生物碱成分，其通过一种尚不明确的机制降低大鼠体重。下丘脑是大脑中与食物摄入和能量消耗控制相关的区域之一。我们推测Evo通过调节下丘脑中与进食相关的肽来介导这一活动。我们研究了Evo对雄性大鼠食物摄入、体重、下丘脑中与进食相关肽的mRNA表达和肽水平的影响。实验开始时使用5周龄的幼鼠。Evo（40mg/kg或4mg/kg）灌胃给药25天，每天记录大鼠的食物摄入量和体重。采集血样进行瘦素放射免疫分析（RIA）。采用实时定量PCR分析mRNA表达。采用蛋白质免疫印迹法和免疫组织化学法分析肽。我们的结果表明，灌胃给予Evo（40mg/kg）可降低大鼠生长后食物摄入率和体重增加，降低下丘脑弓状核（ARC）中促食欲神经肽Y（NPY）和刺鼠基因相关蛋白（AgRP）的mRNA水平以及NPY肽水平，但会增加瘦素的循环水平。灌胃给予较小剂量的Evo（4mg/kg）无效。这些数据表明，Evo部分通过下调下丘脑ARC中NPY和AgRP的mRNA表达及肽表达来减少食物摄入，进而降低体重。
