Hordenine protects against hyperglycemia-associated renal complications in streptozotocin-induced diabetic mice
Hordenine protects against hyperglycemia-associated renal complications in streptozotocin-induced diabetic mice
复制标题
大麦芽碱可预防链脲佐菌素诱导的糖尿病小鼠的高血糖相关肾脏并发症
DOI：
10.1016/j.biopha.2018.05.036
复制
发表时间：
2018-08-01
影响因子：
7.5
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Su, Shuhao;Cao, Meng;Wang, Xin
糖尿病和相关代谢疾病的全球流行率急剧增加。糖尿病的药物治疗仍然有限。大麦碱（HOR）是一种苯乙胺生物碱，是许多植物中的天然成分。本研究旨在探讨HOR对链脲佐菌素（STZ）诱导的糖尿病小鼠的抗糖尿病作用。HOR和胰岛素联合治疗显著降低糖尿病小鼠的空腹和餐后血糖水平。HOR和胰岛素对胰腺结构和功能损伤均无明显保护作用。HOR或胰岛素治疗可明显改善肾组织学和功能损伤。此外，HOR和胰岛素联合治疗导致糖尿病小鼠肾脏组织学和功能损伤的更显着改善。HOR可诱导糖尿病小鼠肾脏IL-1 α/β和IL-6表达减少，Col 1 α 1和MMP 9表达减少，PAS染色肾小球系膜扩张。HOR显著降低糖尿病小鼠肾脏Nrf 2的表达，增加hnRNPF和hnRNPK的表达。此外，HOR与胰岛素对这些调节因子的表达具有协同作用。HOR能降低糖尿病小鼠肾脏ROS水平和TBARS含量。HOR和胰岛素可抑制糖尿病小鼠肾脏抗氧化酶表达的减少。此外，HOR和胰岛素协同发挥抗氧化作用，对抗糖尿病肾病的氧化损伤。总之，据我们所知，我们首次发现HOR与胰岛素联合具有抗糖尿病、抗炎和抗纤维化作用。HOR与胰岛素协同作用，预防糖尿病肾病。然而，HOR和胰岛素协同作用的分子机制需要阐明。
The worldwide prevalence of diabetes and associated metabolic diseases has dramatically increased. Pharmacological treatment of diabetes is still limited. Hordenine (HOR), a phenethylamine alkaloid, is a natural constituent in many plants. The present study was designed to explore the possible anti-diabetic effect of HOR in streptozotocin (STZ)-induced diabetic mice. Combined treatment of HOR and insulin significantly reduced fasting and postprandial blood glucose level in diabetic mice. HOR and insulin did not show evident protective effect against structural and functional injuries of pancreas. Renal histological and functional injuries were significantly improved by HOR or insulin treatment. Moreover, combined treatment of HOR and insulin resulted in a more significant amelioration of renal histological and functional injuries in diabetic mice. HOR induced a decrease of renal IL-1 alpha/beta and IL-6 expression, and a reduction of Col1 alpha 1 and MMP9 expression and PAS-stained mesangial expansion in glomeruli of diabetic mice. In diabetic mice, HOR significantly decreased Nrf2 expression and increased hnRNPF and hnRNPK expression in kidney. Moreover, HOR showed a synergistic effect with insulin on the expression of these regulators. Renal ROS level and TBARS content in diabetic mice were decreased by HOR. The reduction of renal expression of antioxidant enzymes in diabetic mice was inhibited by HOR and insulin. Furthermore, HOR and insulin function synergistically to play an antioxidant role against oxidative injury in diabetic nephropathy. In conclusion, to the best of our knowledge, we, for the first time, found the anti-diabetic, anti-inflammatory, and anti-fibrotic role of HOR in combination with insulin. HOR functions synergistically with insulin and prevents diabetic nephropathy. However, the molecular mechanism of the synergistic effect of HOR and insulin needs to be elucidated.