Saha Sukanya, Sadhukhan Pritam, Sinha Krishnendu, Agarwal Namrata, Sil Parames C
Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.
Biochem Biophys Rep. 2016 Jan 14;5:313-327. doi: 10.1016/j.bbrep.2016.01.011. eCollection 2016 Mar.
Mangiferin is a polyphenolic xanthonoid with remarkable antioxidant activity. Oxidative stress plays the key role in tert-butyl hydroperoxide (tBHP) induced renal cell damage. In this scenario, we consider mangiferin, as a safe agent in tBHP induced renal cell death and rationalize its action systematically, in normal human kidney epithelial cells (NKE).
NKE cells were exposed to 20 µM mangiferin for 2 h followed by 50 µM tBHP for 18 h. The effect on endogenous ROS production, antioxidant status (antioxidant enzymes and thiols), mitochondrial membrane potential, apoptotic signaling molecules, PI3K mediated signaling cascades and cell cycle progression were examined using various biochemical assays, FACS and immunoblot analyses.
tBHP exposure damaged the NKE cells and decreased its viability. It also elevated the intracellular ROS and other oxidative stress-related biomarkers within the cells. However, mangiferin dose dependently, exhibited significant protection against this oxidative cellular damage. Mangiferin inhibited tBHP induced activation of different pro-apoptotic signals and thus protected the renal cells against mitochondrial permeabilization. Further, mangiferin enhanced the expression of cell proliferative signaling cascade molecules, Cyclin d1, NFκB and antioxidant molecules HO-1, SOD2, by PI3K/Akt dependent pathway. However, the inhibitor of PI3K abolished mangiferin's protective activity.
Results show Mangiferin maintains the intracellular anti-oxidant status, induces the expression of PI3K and its downstream molecules and shields NKE cells against the tBHP induced cytotoxicity.
Mangiferin can be indicated as a therapeutic agent in oxidative stress-mediated renal toxicity. This protective action of mangiferin primarily attributes to its potent antioxidant and antiapoptotic nature.
芒果苷是一种具有显著抗氧化活性的多酚类呫吨酮。氧化应激在叔丁基过氧化氢（tBHP）诱导的肾细胞损伤中起关键作用。在这种情况下，我们认为芒果苷在tBHP诱导的肾细胞死亡中是一种安全的药物，并在正常人肾上皮细胞（NKE）中系统地阐明其作用机制。
将NKE细胞暴露于20μM芒果苷中2小时，然后再暴露于50μM tBHP中18小时。使用各种生化分析、流式细胞术和免疫印迹分析来检测对内源性活性氧生成、抗氧化状态（抗氧化酶和硫醇）、线粒体膜电位、凋亡信号分子、PI3K介导的信号级联反应和细胞周期进程的影响。
tBHP暴露会损伤NKE细胞并降低其活力。它还会升高细胞内的活性氧和其他与氧化应激相关的生物标志物。然而，芒果苷呈剂量依赖性地对这种氧化细胞损伤表现出显著的保护作用。芒果苷抑制了tBHP诱导的不同促凋亡信号的激活，从而保护肾细胞免受线粒体通透性改变的影响。此外，芒果苷通过PI3K/Akt依赖性途径增强了细胞增殖信号级联分子Cyclin d1、NFκB以及抗氧化分子HO-1、SOD2的表达。然而，PI3K抑制剂消除了芒果苷的保护活性。
结果表明，芒果苷维持细胞内抗氧化状态，诱导PI3K及其下游分子的表达，并保护NKE细胞免受tBHP诱导的细胞毒性。
芒果苷可作为氧化应激介导的肾毒性的治疗药物。芒果苷的这种保护作用主要归因于其强大的抗氧化和抗凋亡特性。
