Yang Ping, Zhou Yuping, Xia Qing, Yao Lipeng, Chang Xiuchun
Ningbo College of Health Sciences.
The Affiliated Hospital of Medical School of Ningbo University.
Biol Pharm Bull. 2019 May 1;42(5):721-727. doi: 10.1248/bpb.b18-00854. Epub 2019 Mar 13.
Astragaloside IV (AS-IV) is one of the main pharmacologically active compounds found in Astragalus membranaceus. AS-IV has protective effects against ischemia-reperfusion injury (IRI), but its mechanism of action has not yet been determined. This study aims to investigate the effect of AS-IV on IRI and its effect on the phosphadylinositol 3-kinase (PI3K)/Akt/heme oxygenase (HO-1) signaling pathway through in vitro experiments. Firstly, a cell culture model of myocardiocyte hypoxia-reoxygenation (H/R) injury was replicated. After AS-IV treatment, cell viability, reactive oxygen species (ROS) levels, as well as the content or activity of the cellular factors lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), were measured to evaluate the effect of treatment with AS-IV. The effect of AS-IV on HO-1 protein expression and nuclear factor E2-related factor 2 (Nrf2) and Bach1 protein expression was determined by Western blotting. Finally, a reversal of the effect of AS-IV treatment was observed following co-incubation with a PI3K inhibitor. Our results show that AS-IV has good protective effect on H/R injury and has anti-oxidative stress and anti-inflammatory effects. It can regulate the expression of Nrf2 and Bach1 proteins in the nucleus and promote the expression of HO-1 protein, while a PI3K inhibitor can partially reverse the above effects. This study suggests that the PI3K/Akt/HO-1 signaling pathway may be a key signaling pathway for the anti-IRI effect of AS-IV.
黄芪甲苷IV(AS-IV)是黄芪中发现的主要药理活性化合物之一。AS-IV对缺血再灌注损伤(IRI)具有保护作用,但其作用机制尚未确定。本研究旨在通过体外实验探讨AS-IV对IRI的影响及其对磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/血红素加氧酶(HO-1)信号通路的影响。首先,复制心肌细胞缺氧复氧(H/R)损伤的细胞培养模型。AS-IV处理后,检测细胞活力、活性氧(ROS)水平以及细胞因子乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)的含量或活性,以评估AS-IV处理的效果。通过蛋白质印迹法测定AS-IV对HO-1蛋白表达以及核因子E2相关因子2(Nrf2)和Bach1蛋白表达的影响。最后,在与PI3K抑制剂共同孵育后观察到AS-IV处理效果的逆转。我们的结果表明,AS-IV对H/R损伤具有良好的保护作用,具有抗氧化应激和抗炎作用。它可以调节细胞核中Nrf2和Bach1蛋白的表达,促进HO-1蛋白的表达,而PI3K抑制剂可以部分逆转上述作用。本研究表明,PI3K/Akt/HO-1信号通路可能是AS-IV抗IRI作用的关键信号通路。