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苦瓜中一种葫芦烷型三萜类化合物对四氧嘧啶诱导的糖尿病小鼠的抗糖尿病活性

Antidiabetic activities of a cucurbitane‑type triterpenoid compound from Momordica charantia in alloxan‑induced diabetic mice.

作者信息

Jiang Bowen, Ji Mingli, Liu Wei, Chen Lili, Cai Zhiyu, Zhao Yuqing, Bi Xiuli

机构信息

College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China.

Department of Physiology, College of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.

出版信息

Mol Med Rep. 2016 Nov;14(5):4865-4872. doi: 10.3892/mmr.2016.5800. Epub 2016 Oct 5.

Abstract

Momordica charantia has been used to treat a variety of diseases, including inflammation, diabetes and cancer. A cucurbitane‑type triterpenoid [(19R,23E)‑5β, 19‑epoxy‑19‑methoxy‑cucurbita‑6,23,25‑trien‑3 β‑o‑l] previously isolated from M. charantia was demonstrated to possess significant cytotoxicity against cancer cells. The current study investigated the effects of this compound (referred to as compound K16) on diabetes using an alloxan‑induced diabetic mouse model. C57BL/6J mice were intraperitoneally injected with alloxan (10 mg/kg body weight), and those with blood glucose concentration higher than 10 mM were selected for further experiments. Diabetic C57BL/6J mice induced by alloxan were administered 0.9% saline solution, metformine (10 mg/kg body weight), or K16 (25 or 50 mg/kg body weight) by gavage for 4 weeks, followed by analysis of blood glucose level, glucose tolerance, serum lipid levels and organ indexes. The results demonstrated that compound K16 significantly reduced blood glucose (31‑48.6%) and blood lipids (13.5‑42.8%; triglycerides and cholesterol), while improving glucose tolerance compared with diabetic mice treated with saline solution, suggesting a positive improvement in glucose and lipid metabolism following K16 treatment. Furthermore, similarly to metformine, compound K16 markedly upregulated the expression of a number of insulin signaling pathway‑associated proteins, including insulin receptor, insulin receptor substrate 1, glycogen synthase kinase 3β, Akt serine/threonine kinase, and the transcript levels of glucose transporter type 4 and AMP‑activated protein kinase α1. The results of the current study demonstrated that compound K16 alleviated diabetic metabolic symptoms in alloxan‑induced diabetic mice, potentially by affecting genes and proteins involved in insulin metabolism signaling.

摘要

苦瓜已被用于治疗多种疾病,包括炎症、糖尿病和癌症。先前从苦瓜中分离出的一种葫芦烷型三萜类化合物[(19R,23E)-5β,19-环氧-19-甲氧基-葫芦-6,23,25-三烯-3β-醇]被证明对癌细胞具有显著的细胞毒性。本研究使用四氧嘧啶诱导的糖尿病小鼠模型研究了该化合物(称为化合物K16)对糖尿病的影响。将C57BL/6J小鼠腹腔注射四氧嘧啶(10mg/kg体重),选择血糖浓度高于10mM的小鼠进行进一步实验。对四氧嘧啶诱导的糖尿病C57BL/6J小鼠通过灌胃给予0.9%生理盐水、二甲双胍(10mg/kg体重)或K16(25或50mg/kg体重),持续4周,随后分析血糖水平、葡萄糖耐量、血脂水平和器官指数。结果表明,与用生理盐水治疗的糖尿病小鼠相比,化合物K16显著降低了血糖(31%-48.6%)和血脂(13.5%-42.8%;甘油三酯和胆固醇),同时改善了葡萄糖耐量,表明K16治疗后糖脂代谢有积极改善。此外,与二甲双胍类似,化合物K16显著上调了一些胰岛素信号通路相关蛋白的表达,包括胰岛素受体、胰岛素受体底物1、糖原合酶激酶3β、Akt丝氨酸/苏氨酸激酶,以及葡萄糖转运蛋白4和AMP激活蛋白激酶α1的转录水平。本研究结果表明,化合物K16可能通过影响胰岛素代谢信号相关的基因和蛋白,减轻了四氧嘧啶诱导的糖尿病小鼠的糖尿病代谢症状。

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