The Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, China.
The Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, China.
Biomed Pharmacother. 2018 Mar;99:422-430. doi: 10.1016/j.biopha.2018.01.051.
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 TNFɑ 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.
糖尿病影响着全世界很大一部分人群，肾脏是糖尿病并发症的主要靶器官。姜酮是一种从干姜根茎中提取的稳定的活性成分。我们研究了姜酮对糖尿病肾病的影响，并探讨了其可能的机制。结果表明，姜酮降低了血清胰岛素、C 肽和糖化血红蛋白 A1c 的水平。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，姜酮减轻了肾脏的病理损伤，减少了鲍曼囊、鲍曼腔、肾小球簇的表面积，并降低了 db/db 小鼠肾脏中胶原 IV 和纤维连接蛋白的表达。甘油三酯和胆固醇水平升高，TNFɑ 和 IL-6 表达升高，均被姜酮降低。此外，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 小鼠肾脏和高糖暴露后的 HK-2 细胞中表达显著增加。姜酮显著降低了体内和体外的 NOX4 表达。NOX4 的上调显著抑制了姜酮对高糖细胞毒性的保护作用。NOX4 的下调是姜酮发挥药理学作用和减轻糖尿病肾病的原因。总的来说，姜酮是一种有前途的治疗方法，可减轻糖尿病肾病。
