Zingerone attenuates diabetic nephropathy through inhibition of nicotinamide adenine dinucleotide phosphate oxidase 4
Zingerone attenuates diabetic nephropathy through inhibition of nicotinamide adenine dinucleotide phosphate oxidase 4
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DOI：
10.1016/j.biopha.2018.01.051
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发表时间：
2018-03-01
影响因子：
7.5
通讯作者：
Liu, Yun
中科院分区：
文献类型：
--
作者：
Cui, Yan;Shi, Yan;Liu, Yun
糖尿病在世界范围内影响着很大比例的人群，肾脏是糖尿病并发症的主要靶器官。姜酮是从干姜中提取的一种稳定的活性成分。我们研究了生姜酮对糖尿病肾病的作用，并探讨了其可能的机制。我们发现姜酮降低了血清胰岛素、c肽和糖化血红蛋白A1c的水平。生姜酮降低了血尿素氮（BUN）、血清肌酐、尿白蛋白含量和白蛋白/肌酐比（ACR）。此外，姜酮还能减轻db/db小鼠肾脏的病理损伤，减少Bowman's被囊、Bowman's间隙、肾小球簇的表面积，降低肾脏IV型胶原和纤维连接蛋白的表达。姜酮降低了高水平的甘油三酯和胆固醇以及高表达的TNF α和IL-6。此外，生姜酮降低了MDA水平，增加了谷胱甘肽（GSH）的含量。NADPH氧化酶4 （NOX4）在db/db小鼠肾脏和HK-2细胞中的表达显著增加。姜酮可显著降低NOX4在体内和体外的表达。NOX4的上调可显著抑制姜酮诱导的抗高糖细胞毒性的保护作用。NOX4的下调是姜酮表现出药理活性和减少糖尿病肾病的原因。综上所述，生姜酮是一种很有前景的治疗糖尿病肾病的药物。
Diabetes affects a large proportion of population wide across the world and kidney is a main target organ of diabetic complications. Zingerone is a stable active component derived from dry ginger rhizome. We investigated the effect of zingerone on diabetic nephropathy and explored the possible mechanisms. We showed that zingerone decreased the levels of serum insulin, C-peptide and glycosylated hemoglobin A1c. The levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR) were reduced by zingerone. Moreover, zingerone attenuated the pathological injuries of kidneys, reduced the surface area of Bowman's capsule, Bowman's space, glomerular tuft, and decreased the expression of collagen IV and fibronectin in kidneys in db/db mice. The high levels of triglyceride and cholesterol, and high expression of TNF alpha and IL-6 were decreased by zingerone. Furthermore, zingerone decreased the level of MDA and increased the content of glutathione (GSH). NADPH oxidase 4 (NOX4) expression was significantly increased in kidneys of db/db mice and in HK-2 cells after exposure to high glucose. Zingerone significantly decreased the expression of NOX4 in vivo and in vitro. Upregualtion of NOX4 significantly inhibited zingerone-induced protective effects against the cytotoxicity of high glucose. Downregulation of NOX4 was responsible for zingerone-exhibited pharmacological activities and reduction of diabetic nephropathy. Overall, zingerone is a promising therapeutic treatment to attenuate diabetic nephropathy.