Geniposide reduces development of streptozotocin-induced diabetic nephropathy via regulating nuclear factor-kappa B signaling pathways

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• 作者：Xiaolei Hu ; Xiaomei Zhang ; Guoxi Jin ; Zhaoming Shi ; Weihua Sun and Fengling Chen
• 刊名：Fundamental & Clinical Pharmacology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：31
• 期：1
• 页码：54-63
• 全文大小：1136K
• ISSN：1472-8206

文摘

Renal pathology was a commonly seen complication in patients with diabetes. Geniposide (GPO) was previously demonstrated to modulate glucose metabolism in diabetes. This study was to investigate effects of GPO in streptozotocin-induced diabetic rats and its underlying mechanism. Renal function in diabetic rats was evaluated by levels of serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin. Renal inflammation was appraised by inflammatory cells infiltration and pro-inflammatory cytokines production. Renal monocytes, T lymphocytes infiltration, and intercellular adhesion molecule-1 (ICAM-1) expression were quantitated by immunohistochemistry. Moreover, renal nuclear factor-kappa B (NF-κB) was assayed by Western blotting. Diabetic rats showed renal dysfunction as evidenced by increased levels of Scr, BUN, urinary albumin, and elevator renal index. Histological examination revealed significant glomerular basement membrane (GBM) thickening. However, GPO notably improved renal function and diabetes-induced GBM changes. Additionally, diabetic rats showed noteworthy renal inflammation,as reflected by enhancement of monocytes and T lymphocytes infiltration, increased expression of ICAM-1, tumor necrosis factor-α, interleukin-1 (IL-1), and IL-6. Interestingly, the level of monocytes infiltration positively correlated with the severity of GBM. Further study indicated diabetic rats displayed increased activation of NF-κB, indicated by increased expression of NF-κB p65, IKKα, and p-IκBα in renal tissue. However, all the changes in renal inflammation and NF-κB pathway were obviously reversed in GPO-treated diabetic rats. Our works indicate GPO ameliorates structural and functional abnormalities of kidney in diabetic rats, which is associated with its suppression of NF-κB-mediated inflammatory response.