Lv Xing, Dai Guoying, Lv Gaohong, Chen Yuping, Wu Yunhao, Shen Hongsheng, Xu Huiqin
Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine, Nanjing, Jiangsu 210023, China.
Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine, Nanjing, Jiangsu 210023, China.
J Ethnopharmacol. 2016 Jun 5;185:110-9. doi: 10.1016/j.jep.2016.03.017. Epub 2016 Mar 10.
Rehmanniae Radix (RR) and Cornus officinalis (CO) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic nephropathy. Iridoid glycoside of Cornus officinalis (IGCO), triterpenoid acid of Cornus officinalis (TACO) and iridoid glycoside of Rehmanniae Radix (IGRR) formed an innovative formula named combinatorial bioactive parts (CBP). The aims of the present study were to investigate the renoprotective effects of CBP on DN through the inhibition of AGEs/RAGE/SphK1 signaling pathway activation, and identify the advantage of CBP compared with IGCO, TACO, IGRR.
The db/db diabetic renal injury model was used to examine the renoprotective effects of CBP, IGCO, TACO and IGRR. For mechanistic studies, diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGEs/RAGE/SphK1 pathway were determined.
CBP, IGCO, TACO and IGRR inhibited the decrease in serum insulin levels and the increases in urine volume, food consumption, water intake, TC, TG, glycated serum protein, fasting blood glucose levels, 24h urine protein levels, and serum levels of urea nitrogen and creatinine. It also prevented ECM accumulation and improved the histology of pancreas and kidney, and alleviated the structural alterations in mesangial cells and podocytes in renal cortex. Moreover, CBP, IGCO, TACO and IGRR down-regulated the elevated staining, protein levels of RAGE, SphK1, TGF-β and NF-κB. Among the treatment groups, CBP produced the strongest effects.
These findings suggest that the inhibitory effect of CBP, IGCO, TACO and IGRR on the activation of AGEs/RAGE/SphK1 signaling pathway in db/db diabetic mice kidney is a novel mechanism by which CBP, IGCO, TACO and IGRR exerts renoprotective effects on DN. Among all the groups, CBP produced the strongest effect while IGCO, TACO and IGRR produced weaker effects.
地黄（RR）和山茱萸（CO）是中国广泛用于治疗糖尿病及其并发症（如糖尿病肾病）的两种传统中药。山茱萸的环烯醚萜苷（IGCO）、山茱萸的三萜酸（TACO）和地黄的环烯醚萜苷（IGRR）形成了一种名为组合生物活性成分（CBP）的创新配方。本研究的目的是通过抑制晚期糖基化终末产物/晚期糖基化终末产物受体/鞘氨醇激酶1（AGEs/RAGE/SphK1）信号通路激活来研究CBP对糖尿病肾病的肾脏保护作用，并确定CBP与IGCO、TACO、IGRR相比的优势。
使用db/db糖尿病肾损伤模型来研究CBP、IGCO、TACO和IGRR的肾脏保护作用。对于机制研究，评估糖尿病症状、肾功能以及胰腺和肾脏的病理组织学。检测AGEs/RAGE/SphK1信号通路。
CBP、IGCO、TACO和IGRR抑制血清胰岛素水平的降低以及尿量、食物摄入量、饮水量、总胆固醇（TC）、甘油三酯（TG）、糖化血清蛋白、空腹血糖水平、24小时尿蛋白水平以及血清尿素氮和肌酐水平的升高。它还防止细胞外基质（ECM）积聚，改善胰腺和肾脏的组织学，并减轻肾皮质系膜细胞和足细胞的结构改变。此外，CBP、IGCO、TACO和IGRR下调RAGE、SphK1、转化生长因子-β（TGF-β）和核因子-κB（NF-κB）升高的染色和蛋白水平。在各治疗组中，CBP产生的效果最强。
这些发现表明，CBP、IGCO、TACO和IGRR对db/db糖尿病小鼠肾脏中AGEs/RAGE/SphK1信号通路激活的抑制作用是CBP、IGCO、TACO和IGRR对糖尿病肾病发挥肾脏保护作用的一种新机制。在所有组中，CBP产生的效果最强，而IGCO、TACO和IGRR产生的效果较弱。
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