Previous studies revealed a cardioprotective potential of Panax notoginseng to relieve acute myocardial infarction and focal cerebral ischemia-reperfusion. However, whether P. notoginseng protects endothelial function in diabetes and the underlying mechanisms remain to be explored. P. notoginseng contains several chemical components including saponins, which are commonly believed as the major bioactive ingredients. The present study was aimed to examine and compare the vaso-protective effects of the ethanolic extract of P. notoginseng (PNE) and total saponin (PNS). Both aortas and carotid arteries were isolated from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) with and without the presence of PNS and PNE. Diabetic model was established by feeding the mice with a high-fat diet (45% kcal% fat) for 12 weeks, while PNS and PNE were administrated by oral gavage at 20 mg/kg/day for another 4 weeks. Ex vivo exposure to high glucose impaired acetylcholine-induced endothelium-dependent relaxations in mouse aortas, decreased phosphorylation of AMPK and eNOS, and induced endoplasmic reticulum (ER) stress and oxidative stress. These effects were reversed by cotreatment of PNS and PNE with PNS being more potent. Furthermore, the vaso-protective effects were abolished by Compound C (AMPK inhibitor). Chronic treatment with PNS and PNE improved endothelium-dependent relaxations and alleviated ER stress and oxidative stress in aortas from high-fat diet-induced obese mice. PNE was more effective to improve glucose sensitivity and normalize blood pressure in diabetic mice. The present results showed that PNS and PNE reduced ER stress and oxidative stress and, subsequently, improved endothelial function in diabetes through AMPK activation. This study provides new inspiration on the therapeutic potential of P. notoginseng extract against vascular diseases associated with metabolic disorders.

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三七预防糖尿病相关的内皮功能障碍：乙醇提取物和总皂苷的比较

以前的研究表明，三七对缓解急性心肌梗死和局灶性脑缺血再灌注具有心脏保护作用。然而，三七是否保护糖尿病患者的内皮功能及其潜在机制仍有待探索。三七含有几种化学成分，包括皂苷，通常被认为是主要的生物活性成分。本研究旨在检查和比较三七乙醇提取物(PNE) 和总皂苷 (PNS) 的血管保护作用。主动脉和颈动脉均从雄性 C57BL/6J 小鼠体外分离在存在和不存在 PNS 和 PNE 的情况下使用危险因素（高葡萄糖或衣霉素）进行治疗。通过给小鼠喂食高脂饮食（45% kcal% 脂肪）12 周建立糖尿病模型，同时以 20 mg/kg/天的剂量口服管饲法给予 PNS 和 PNE 4 周。离体暴露于高葡萄糖会损害乙酰胆碱诱导的小鼠主动脉内皮依赖性舒张，降低 AMPK 和 eNOS 的磷酸化，并诱导内质网 (ER) 应激和氧化应激。PNS 和 PNE 的共同治疗可以逆转这些影响，PNS 更有效。此外，化合物C（AMPK抑制剂）消除了血管保护作用。PNS 和 PNE 的慢性治疗改善了高脂饮食诱导的肥胖小鼠的内皮依赖性松弛，并减轻了主动脉中的 ER 应激和氧化应激。PNE 对改善糖尿病小鼠的葡萄糖敏感性和使血压正常化更有效。目前的结果表明，PNS 和 PNE 降低了 ER 应激和氧化应激，随后通过 AMPK 激活改善了糖尿病患者的内皮功能。三七提取物对抗与代谢紊乱相关的血管疾病。