Laboratorio de Productos Naturales, Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, PO Box 8380492, Santos Dumont 964, Santiago, Chile.
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28925, Madrid, Spain.
Sci Rep. 2019 Jan 24;9(1):599. doi: 10.1038/s41598-018-36555-1.
Infusions of murtilla leaves exhibit antioxidant, analgesic, and anti-inflammatory properties. Several compounds that are structurally similar to madecassic acid (MA), a component of murtilla leaf extract (ethyl acetate extract, EAE), have been shown to inhibit protein tyrosine phosphatase 1B (PTP1P). The aim of this study was to evaluate if EAE and two compounds identified in EAE (MA and myricetin [MYR]) could have a beneficial effect on systemic and vascular insulin sensitivity and endothelial function in a model of diet-induced obesity. Experiments were performed in 5-week-old male C57BL6J mice fed with a standard (LF) or a very high-fat diet (HF) for 4 weeks and treated with EAE, MA, MYR, or the vehicle as control (C). EAE significantly inhibited PTP1B. EAE and MA, but not MYR, significantly improved systemic insulin sensitivity in HF mice and vascular relaxation to Ach in aorta segments, due to a significant increase of eNOS phosphorylation and enhanced nitric oxide availability. EAE, MA, and MYR also accounted for increased relaxant responses to insulin in HF mice, thus evidencing that the treatments significantly improved aortic insulin sensitivity. This study shows for the first time that EAE and MA could constitute interesting candidates for treating insulin resistance and endothelial dysfunction associated with obesity.
悬钩子叶提取物具有抗氧化、镇痛和抗炎作用。已经证明，几种结构上与玛蒂酸（MA）相似的化合物（MA 是悬钩子叶提取物（乙酸乙酯提取物，EAE）的一种成分）能够抑制蛋白酪氨酸磷酸酶 1B（PTP1B）。本研究旨在评估 EAE 以及在 EAE 中鉴定出的两种化合物（MA 和杨梅素[MYR]）是否可以对饮食诱导肥胖模型中的全身和血管胰岛素敏感性以及内皮功能产生有益影响。实验在 5 周龄雄性 C57BL6J 小鼠中进行，这些小鼠喂食标准（LF）或高脂肪饮食（HF）4 周，并接受 EAE、MA、MYR 或作为对照的载体（C）治疗。EAE 显著抑制 PTP1B。EAE 和 MA 但不是 MYR 可显著改善 HF 小鼠的全身胰岛素敏感性，并改善主动脉段对 Ach 的血管舒张作用，这归因于 eNOS 磷酸化的显著增加和一氧化氮可用性的增强。EAE、MA 和 MYR 还导致 HF 小鼠对胰岛素的舒张反应增加，从而表明这些治疗方法显著改善了主动脉胰岛素敏感性。本研究首次表明，EAE 和 MA 可能是治疗与肥胖相关的胰岛素抵抗和内皮功能障碍的有前途的候选药物。
