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Aucubin alleviates diabetic nephropathy by inhibiting NF-κB activation and inducing SIRT1/SIRT3-FOXO3a signaling pathway in high-fat diet/streptozotocin-induced diabetic mice
Journal of Functional Foods ( IF 5.6 ) Pub Date : 2019-12-12 , DOI: 10.1016/j.jff.2019.103702
Bo Ma , Zhiming Zhu , Jie Zhang , Chaoxing Ren , Qi Zhang

Oxidative stress and inflammation are two important pathological mechanisms in diabetic nephropathy (DN). Aucubin (AU), a natural iridoid glucoside, possessing remarkable anti-inflammatory and anti-oxidation activity, has been used to treat diabetic complications. However, underlying mechanism of protective action in DN remains unclear. In the present study, AU significantly alleviated albuminuria, glomerular extracellular matrix expansion, renal fibrosis, and inflammation caused by diabetes after ten weeks of treatment. Moreover, AU significantly inhibited oxidative stress markers in kidney tissue. In addition, we demonstrated that AU promoted endogenous antioxidant defenses by triggering Nrf2 and FOXO3a nuclear translocation, respectively, and up-regulation of antioxidant genes, including NQO1, HO-1, Mn-SOD, and CAT. These effects may be, in part, mediated by inducing SIRT1 and SIRT3 activities. Furthermore, AU also attenuated pro-inflammatory cytokines in renal tissue by inhibiting the NF-κB signaling pathway. Taken together, our results suggested that AU is a potential natural agent for the prevention of diabetes-induced DN.



中文翻译:

蜂胶通过抑制高脂饮食/链脲佐菌素诱导的糖尿病小鼠中的NF-κB活化并诱导SIRT1 / SIRT3-FOXO3a信号通路来减轻糖尿病肾病

氧化应激和炎症是糖尿病肾病(DN)的两个重要病理机制。蜂胶(AUCUBIN)是一种天然的鸢尾花糖苷,具有显着的抗炎和抗氧化活性,已被用于治疗糖尿病并发症。但是,尚不清楚DN中保护作用的基本机制。在本研究中,治疗十周后,AU显着缓解了蛋白尿,肾小球细胞外基质扩张,肾纤维化和糖尿病引起的炎症。此外,非盟显着抑制肾脏组织中的氧化应激标志物。此外,我们证明了非盟分别通过触发Nrf2和FOXO3a核易位并上调抗氧化剂基因(包括NQO1,HO-1,Mn-SOD和CAT)来促进内源性抗氧化剂防御。这些影响可能是 部分是通过诱导SIRT1和SIRT3活性介导的。此外,AU还通过抑制NF-κB信号传导途径减弱了肾脏组织中的促炎细胞因子。两者合计,我们的结果表明非盟是一种潜在的天然药物,以预防糖尿病引起的DN。

更新日期:2019-12-13
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