Araújo Tiago Gomes, de Oliveira Alexandre Gabarra, Vecina Juliana Falcato, Marin Rodrigo Miguel, Franco Eryvelton Souza, Abdalla Saad Mario J, de Sousa Maia Maria Bernadete
Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil; Department of Internal Medicine, State University of Campinas, 13081-970 Campinas, SP, Brazil.
Department of Internal Medicine, State University of Campinas, 13081-970 Campinas, SP, Brazil; Department of Physical Education, São Paulo State University (UNESP), 13506-900 Rio Claro, SP, Brazil.
J Ethnopharmacol. 2016 May 13;183:95-102. doi: 10.1016/j.jep.2016.02.048. Epub 2016 Mar 3.
The search for natural agents that minimize obesity-associated disorders is receiving special attention. Parkinsonia aculeata L. (Caesalpineaceae) has long been used in Brazil as a hypoglycaemic herbal medicine, without any scientific basis.
In this context, we aimed to use molecular and physiological methods to study the effect of a hydroethanolic extract partitioned with ethyl acetate from the aerial parts of Parkinsonia aculeata (HEPa/EtOAc) on insulin resistance in a mouse model of diet-induced obesity (DIO).
Firstly, C57BL/6J mice were fed either with standard rodent chow diet or a high-fat diet (HFD) for 12 consecutive weeks. Then, the animals were treated with HEPa/EtOAc at two doses (125 and 250mg/kg/day) or metformin (200mg/kg/day) for 16 days. At the end of the experiment, body weight, fat pad weight, fasting serum glucose (FSG), insulin (FSI) and leptin were measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. Glucose, insulin and pyruvate tolerance tests were performed. The expression and phosphorylation of IRβ(tyr), Akt(ser473), AMPKα and PGC1α in liver, muscle and adipose tissue were determined by Western blot analyses.
Herein we demonstrate for the first time an improvement in insulin resistance following HEPa/EtOAc administration in obese mice, as shown by increased glucose, insulin and pyruvate tolerance, as well as an improvement in FSG, FSI, HOMA-IR and circulating leptin levels, which together are in part due to enhancement of the insulin signaling pathway in its main target tissues. Surprisingly, the increase in activation of the AMPKα-PGC1-α axis by HEPa/EtOAc was similar to that produced by metformin treatment in the liver and muscle tissues.
In conclusion, P. aculeata appears to be a source of therapeutic agent against obesity-related complications.
寻找能将肥胖相关疾病降至最低的天然药物受到了特别关注。刺蒺藜（豆科）在巴西长期被用作降血糖草药，但并无任何科学依据。
在此背景下，我们旨在运用分子和生理学方法，研究刺蒺藜地上部分经乙酸乙酯分配的水乙醇提取物（HEPa/EtOAc）对饮食诱导肥胖（DIO）小鼠模型胰岛素抵抗的影响。
首先，将C57BL/6J小鼠连续12周喂食标准啮齿动物饲料或高脂饮食（HFD）。然后，动物分别接受两种剂量（125和250mg/kg/天）的HEPa/EtOAc或二甲双胍（200mg/kg/天）治疗16天。实验结束时，测量体重、脂肪垫重量、空腹血清葡萄糖（FSG）、胰岛素（FSI）和瘦素。还计算了胰岛素抵抗的稳态模型评估（HOMA-IR）。进行了葡萄糖、胰岛素和丙酮酸耐量试验。通过蛋白质免疫印迹分析测定肝脏、肌肉和脂肪组织中IRβ（tyr）、Akt（ser473）、AMPKα和PGC1α的表达及磷酸化。
在此我们首次证明，肥胖小鼠给予HEPa/EtOAc后胰岛素抵抗得到改善，表现为葡萄糖、胰岛素和丙酮酸耐量增加，以及FSG、FSI、HOMA-IR和循环瘦素水平改善，这部分共同归因于其主要靶组织中胰岛素信号通路的增强。令人惊讶的是，HEPa/EtOAc对AMPKα-PGC1-α轴激活的增加与二甲双胍治疗在肝脏和肌肉组织中产生的效果相似。
总之，刺蒺藜似乎是一种治疗肥胖相关并发症的药物来源。
