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马齿苋提取物通过激活糖尿病肥胖小鼠的AMPK减轻内质网应激和氧化应激来保护内皮功能。

L. (Purslane) Extract Protects Endothelial Function by Reducing Endoplasmic Reticulum Stress and Oxidative Stress through AMPK Activation in Diabetic Obese Mice.

作者信息

Miao Lingchao, Zhou Chunxiu, Zhang Haolin, Cheong Meng Sam, Tan Yi, Wang Yuehan, Zhang Xutao, Yu Hua, Cheang Wai San

机构信息

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macau 999078, China.

出版信息

Antioxidants (Basel). 2023 Dec 18;12(12):2132. doi: 10.3390/antiox12122132.

Abstract

L. (purslane) is a food and a traditional drug worldwide. It exhibits anti-inflammatory, anti-oxidative, anti-tumor, and anti-diabetic bioactivities; but its activity on diabetic-associated endothelial dysfunction is unknown. This study aimed to investigate the effect of purslane on endothelial function and the underlying mechanisms. Male C57BL/6 mice had 14-week ad libitum access to a high-fat rodent diet containing 60% kcal% fat to induce obesity and diabetes whereas purslane extract (200 mg/kg/day) was administered during the last 4 weeks via intragastric gavage. Primary rat aortic endothelial cells and isolated mouse aortas were cultured with a risk factor, high glucose or tunicamycin, together with purslane extract. By ESI-QTOF-MS/MS, flavonoids and their glycoside products were identified in the purslane extract. Exposure to high glucose or tunicamycin impaired acetylcholine-induced endothelium-dependent relaxations in aortas and induced endoplasmic reticulum (ER) stress and oxidative stress with the downregulation of 5' AMP-activated protein kinase (AMPK)/ endothelial nitric oxide synthase (eNOS) signaling. Co-incubation with purslane significantly ameliorated these impairments. The effects of purslane were abolished by Compound C (AMPK inhibitor). Four-week purslane treatment ameliorated aortic relaxations, ER stress, and oxidative stress in diabetic obese mice. This study supported that purslane protected endothelial function, and inhibited ER stress and oxidative stress in vasculature through AMPK/eNOS activation, revealing its therapeutic potential against vascular complications in diabetes.

摘要

马齿苋在全球范围内既是一种食物,也是一种传统药物。它具有抗炎、抗氧化、抗肿瘤和抗糖尿病的生物活性;但其对糖尿病相关内皮功能障碍的活性尚不清楚。本研究旨在探讨马齿苋对内皮功能的影响及其潜在机制。雄性C57BL/6小鼠自由摄取含60%千卡脂肪的高脂啮齿动物饮食14周以诱导肥胖和糖尿病,而在最后4周通过灌胃给予马齿苋提取物(200mg/kg/天)。将原代大鼠主动脉内皮细胞和分离的小鼠主动脉与危险因素、高糖或衣霉素以及马齿苋提取物一起培养。通过电喷雾四极杆飞行时间串联质谱(ESI-QTOF-MS/MS),在马齿苋提取物中鉴定出黄酮类化合物及其糖苷产物。暴露于高糖或衣霉素会损害主动脉中乙酰胆碱诱导的内皮依赖性舒张,并诱导内质网(ER)应激和氧化应激,同时下调5'腺苷酸活化蛋白激酶(AMPK)/内皮型一氧化氮合酶(eNOS)信号通路。与马齿苋共同孵育可显著改善这些损伤。Compound C(AMPK抑制剂)消除了马齿苋的作用。四周的马齿苋治疗改善了糖尿病肥胖小鼠的主动脉舒张、ER应激和氧化应激。本研究支持马齿苋通过激活AMPK/eNOS保护内皮功能,并抑制血管中的ER应激和氧化应激,揭示了其对糖尿病血管并发症的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cb7/10741183/6d706a1c4ece/antioxidants-12-02132-g001.jpg

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