Mazumdar Suchismita, Marar Thankamani, Devarajan Shine, Patki Jyoti
School of Biotechnology and Bioinformatics, D.Y.Patil Deemed to Be University, CBD Belapur, Navi Mumbai, India.
Biochem Biophys Rep. 2021 Jan 7;25:100904. doi: 10.1016/j.bbrep.2020.100904. eCollection 2021 Mar.
Clinical evidence suggests that type 2 diabetes therapy can greatly benefit from the suppression of reactive oxygen species generation and the activation or restoration of cellular antioxidant mechanisms. In human, NADPH oxidase (NOX) is the main producer of reactive oxygen species (ROS) that supress the activity of endogenous antioxidant enzymes. In the present study, the antioxidant potential of Gedunin was studied. findings reveal its strong binding affinity with NOX5 C terminal HSP90 binding site that disrupts NOX5 stability and its ability to generate ROS, leading to restoration antioxidant enzymes activities. It was found that Gedunin suppressed hyperglycaemia induced oxidative stress in an RBC model and markedly reversed glucose induced changes including haemoglobin glycosylation and lipid peroxidation. A significant restoration of activities of cellular antioxidant enzymes; superoxide dismutase, catalase and glutathione peroxidase in the presence of Gedunin revealed its ability to reduce oxidative stress. These results substantiated Gedunin as a bona fide inhibitor of human NOX5 and a ROS scavenging antioxidant with promising therapeutic attributes including its natural origin and inhibition of multiple diabetic targets.
临床证据表明，2型糖尿病治疗可从抑制活性氧生成以及激活或恢复细胞抗氧化机制中大大获益。在人体中，NADPH氧化酶（NOX）是抑制内源性抗氧化酶活性的活性氧（ROS）的主要产生者。在本研究中，对格杜宁的抗氧化潜力进行了研究。研究结果揭示了它与NOX5 C末端HSP90结合位点具有很强的结合亲和力，这会破坏NOX5的稳定性及其产生活性氧的能力，从而导致抗氧化酶活性恢复。研究发现，格杜宁在红细胞模型中抑制了高血糖诱导的氧化应激，并显著逆转了葡萄糖诱导的变化，包括血红蛋白糖基化和脂质过氧化。在存在格杜宁的情况下，细胞抗氧化酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性显著恢复，这表明其具有减轻氧化应激的能力。这些结果证实格杜宁是一种真正的人NOX5抑制剂，也是一种具有清除活性氧功能的抗氧化剂，具有包括天然来源和抑制多种糖尿病靶点在内的有前景的治疗特性。
