Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats.
Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats.
复制标题
黄蜀葵总黄酮通过抑制 iRhom2/TACE 信号通路活性改善大鼠糖尿病肾病
DOI：
10.1080/13880209.2017.1412467
复制
发表时间：
2017-12
影响因子：
3.8
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Liu S;Ye L;Tao J;Ge C;Huang L;Yu J
摘要背景：黄蜀葵总黄酮(TFA)已被临床证明能有效改善慢性肾脏疾病(CKD)的肾炎症和肾小球损伤。目的：本研究通过建立糖尿病肾病大鼠模型，评价三七总皂甙对肿瘤坏死因子-α转换酶信号转导的抑制作用，并观察其抗糖尿病肾病的作用。材料和方法：体外培养细胞，加入2 0 0 μg/mL晚期糖基化终产物(AGEs)，再与2 0 μg/mLTFA共培养2 4 h，采用实时荧光定量聚合酶链式反应、免疫印迹和免疫共沉淀等方法。8周龄雄性SD大鼠采用单侧肾切除加链脲佐菌素腹腔注射的方法建立糖尿病肾病模型，分别以3种不同剂量(30 0、135、75 mg/kg/d)灌胃给药12周。4-苯基丁酸(2.5 mg/kg/d)作为阳性对照。结果：TFA对HK2和HRMC的IC50值分别为35.6 μM和39.6 μM。TFA处理(20 μM)可抑制AGEs诱导的IRHOM2/TACE信号的激活。大鼠灌胃LD_(50)26 g/kg和ED_(50)=67 mg/kg时，剂量依赖性地下调促炎细胞因子的表达，并通过抑制IRHOM_2/TACE信号通路的激活而发挥显著的抗炎作用。讨论与结论：我们的结果表明，TFA通过抑制IRHOM2/TACE信号通路的激活和减轻内质网应激，可以剂量依赖性地减轻肾脏炎症。提示TFA在人类糖尿病肾病的治疗中具有潜在的治疗价值。
Abstract Context: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). Objective: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis factor-α converting enzyme) signalling and investigated its anti-DN (diabetic nephropathy) effects in a DN rat model. Materials and methods: In vitro, cells were treated with 200 μg/mL advanced glycation end products (AGEs), and then co-cultured with 20 μg/mL TFA for 24 h. Real time PCR, western blotting and co-immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5 mg/kg/d) was used as a positive control. Results: IC50 of TFA is 35.6 μM in HK2 and 39.6 μM in HRMC. TFA treatment (20 μM) inhibited the activation of iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and ED50=67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the expression of proinflammatory cytokines and exerted anti-inflammatory effects significantly though inhibiting the activation of iRhom2/TACE signalling. Discussion and conclusions: Our results show that TFA could dose-dependently ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE signalling and attenuating ER stress. These results suggest that TFA has potential therapeutic value for the treatment of DN in humans.
登录
查看更多内容
影响因子：
4.6
作者：
Ozcan, Filiz;Ozmen, Asli;Aslan, Mutay
通讯作者：
Aslan, Mutay
DOI：
10.3109/10409231003628015
发表时间：
2010-04
影响因子：
6.5
作者：
Gooz M
通讯作者：
Gooz M
影响因子：
2.1
作者：
Duran-Perez, Edgar G.;Almeda-Valdes, Paloma;Gomez-Perez, Francisco J.
通讯作者：
Gomez-Perez, Francisco J.
影响因子：
7.7
作者：
Christova, Yonka;Adrain, Colin;Bambrough, Paul;Ibrahim, Ashraf;Freeman, Matthew
通讯作者：
Freeman, Matthew
SPE-HPLC法测定口服秋葵提取物后大鼠血浆和尿液中4种黄酮醇的含量
DOI：
10.1016/j.jchromb.2006.12.043
发表时间：
2007-06-01
影响因子：
3
作者：
Lai, Xianyin;Zhao, Yuying;Guo, Dean
通讯作者：
Guo, Dean