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绿南非钩麻(Aspalathus linearis)提取物补充对缺血性糖尿病前期大鼠离体心脏的心脏保护作用。

Cardioprotective Function of Green Rooibos (Aspalathus linearis) Extract Supplementation in Ex Vivo Ischemic Prediabetic Rat Hearts.

机构信息

Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Republic of South Africa.

Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Republic of South Africa.

出版信息

Planta Med. 2022 Jan;88(1):62-78. doi: 10.1055/a-1239-9236. Epub 2020 Dec 7.

Abstract

Diabetic patients develop ischemic heart disease and strokes more readily. Following an ischemic event, restoration of blood flow increases oxidative stress resulting in myocardial damage, termed ischemia/reperfusion injury. Aspalathus linearis (rooibos), rich in the antioxidant phenolic compound aspalathin, has been implicated as cardioprotective against ischemia/reperfusion injury with undefined mechanism in control rats. Primarily, the therapeutic potential of Afriplex green rooibos extract to prevent ischemia/reperfusion injury in cardiovascular disease-compromised rats was investigated. Additionally, Afriplex Green rooibos extract's cardioprotective signaling on metabolic markers and stress markers was determined using western blotting. Three hundred male Wistar rats received either 16-wk standard diet or high-caloric diet. During the final 6 wk, half received 60 mg/kg/day Afriplex green rooibos extract, containing 12.48% aspalathin. High-caloric diet increased body weight, body fat, fasting serum triglycerides, and homeostatic model assessment of insulin resistance - indicative of prediabetes. High-caloric diet rats had increased heart mass, infarct size, and decreased heart function. Afriplex green rooibos extract treatment for 6 wk lowered pre-ischemic heart rate, reduced infarct size, and improved heart function pre- and post-ischemia, without significantly affecting biometric parameters. Stabilized high-caloric diet hearts had decreased insulin independence via adenosine monophosphate activated kinase and increased inflammation (p38 mitogen-activated protein kinase), whereas Afriplex green rooibos extract treatment decreased insulin dependence (protein kinase B) and conferred anti-inflammatory effect. After 20 min ischemia, high-caloric diet hearts had upregulated ataxia-telangiectasia mutated kinase decreased insulin independence, and downregulated insulin dependence and glycogen synthase kinase 3 inhibition. In contrast, Afriplex green rooibos extract supplementation downregulated insulin independence and inhibited extracellular signal-regulated kinase 1 and 2. During reperfusion, all protective signaling was decreased in high-caloric diet, while Afriplex green rooibos extract supplementation reduced oxidative stress (c-Jun N-terminal kinases 1 and 2) and inflammation. Taken together, Afriplex green rooibos extract supplementation for 6 wk preconditioned cardiovascular disease-compromised rat hearts against ischemia/reperfusion injury by lowering inflammation, oxidative stress, and heart rate.

摘要

糖尿病患者更容易发生缺血性心脏病和中风。在发生缺血事件后,血流恢复会增加氧化应激,导致心肌损伤,称为缺血/再灌注损伤。富含抗氧化酚类化合物 aspalathin 的 Aspalathus linearis(罗布斯塔茶)被认为对缺血/再灌注损伤具有保护作用,但在对照大鼠中其作用机制尚不清楚。本研究主要探讨 Afriplex 绿罗布斯塔提取物在心血管疾病受损大鼠中预防缺血/再灌注损伤的治疗潜力。此外,还使用 Western blot 测定了 Afriplex 绿罗布斯塔提取物对代谢标志物和应激标志物的心脏保护信号。300 只雄性 Wistar 大鼠分别给予 16 周标准饮食或高热量饮食。在最后 6 周,一半大鼠给予 60mg/kg/天的 Afriplex 绿罗布斯塔提取物,其中含有 12.48% aspalathin。高热量饮食增加了体重、体脂肪、空腹血清甘油三酯和稳态模型评估的胰岛素抵抗 - 表明存在前驱糖尿病。高热量饮食大鼠的心脏质量增加、梗死面积增加、心功能降低。Afriplex 绿罗布斯塔提取物治疗 6 周可降低缺血前心率、减少梗死面积并改善缺血前和缺血后的心功能,而对生物计量参数无显著影响。稳定的高热量饮食心脏通过单磷酸腺苷激活的蛋白激酶降低了胰岛素独立性并增加了炎症(p38 丝裂原激活蛋白激酶),而 Afriplex 绿罗布斯塔提取物治疗降低了胰岛素依赖性(蛋白激酶 B)并发挥了抗炎作用。缺血 20 分钟后,高热量饮食心脏上调了共济失调毛细血管扩张突变激酶,降低了胰岛素独立性,并下调了胰岛素依赖性和糖原合酶激酶 3 抑制。相比之下,Afriplex 绿罗布斯塔提取物补充剂下调了胰岛素独立性并抑制了细胞外信号调节激酶 1 和 2。在再灌注期间,所有保护性信号在高热量饮食中均降低,而 Afriplex 绿罗布斯塔提取物补充剂降低了氧化应激(c-Jun N-末端激酶 1 和 2)和炎症。总之,Afriplex 绿罗布斯塔提取物补充剂预处理 6 周可降低炎症、氧化应激和心率,从而使心血管疾病受损的大鼠心脏免受缺血/再灌注损伤。

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