Zhang Lei, Chen Zhiquan, Gong Wenyan, Zou Yezi, Xu Futian, Chen Lihao, Huang Heqing
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Front Pharmacol. 2018 May 18;9:512. doi: 10.3389/fphar.2018.00512. eCollection 2018.
Diabetic nephropathy (DN) is rapidly becoming the leading cause of end-stage renal disease worldwide and a major cause of morbidity and mortality in patients of diabetes. The main pathological change of DN is renal fibrosis. Paeonol (PA), a single phenolic compound extracted from the root bark of Cortex Moutan, has been demonstrated to have many potential pharmacological activities. However, the effects of PA on DN have not been fully elucidated. In this study, high glucose (HG)-treated glomerular mesangial cells (GMCs) and streptozotocin (STZ)-induced diabetic mice were analyzed in exploring the potential mechanisms of PA on DN. Results showed that: (1) PA inhibited HG-induced fibronectin (FN) and ICAM-1 overexpressions; (2) PA exerted renoprotective effect through activating the Nrf2/ARE pathway; (3) Sirt1 mediated the effects of PA on the activation of Nrf2/ARE pathway. What is more, in accordance with the results, significant elevated levels of Sirt1, Nrf2 and downstream proteins related to Nrf2 were observed in the kidneys of PA treatment group compared with model group. Taken together, our study shows that PA delays the progression of diabetic renal fibrosis, and the underlying mechanism is probably associated with regulating the Nrf2 pathway. The effect of PA on Nrf2 is at least partially dependent on Sirt1 activation.
糖尿病肾病（DN）正迅速成为全球终末期肾病的主要原因，也是糖尿病患者发病和死亡的主要原因。DN的主要病理变化是肾纤维化。丹皮酚（PA）是从牡丹皮根皮中提取的一种单一酚类化合物，已被证明具有许多潜在的药理活性。然而，PA对DN的影响尚未完全阐明。在本研究中，通过分析高糖（HG）处理的肾小球系膜细胞（GMCs）和链脲佐菌素（STZ）诱导的糖尿病小鼠，探讨PA对DN的潜在作用机制。结果表明：（1）PA抑制HG诱导的纤连蛋白（FN）和细胞间黏附分子-1（ICAM-1）的过度表达；（2）PA通过激活Nrf2/ARE通路发挥肾脏保护作用；（3）沉默调节蛋白1（Sirt1）介导PA对Nrf2/ARE通路激活的作用。此外，与模型组相比，PA治疗组小鼠肾脏中Sirt1、Nrf2及Nrf2下游相关蛋白水平显著升高。综上所述，我们的研究表明，PA可延缓糖尿病肾纤维化的进展，其潜在机制可能与调节Nrf2通路有关。PA对Nrf2的作用至少部分依赖于Sirt1的激活。
