Nephrology Department, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, Jiangsu, 215006, China.
Emergency Department, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, Jiangsu 212001, China.
Biosci Rep. 2018 Aug 29;38(4). doi: 10.1042/BSR20180444. Print 2018 Aug 31.
The current study was designed to investigate the protective effect and possible mechanisms of umbelliferone (Umb) on liver injury in diabetic C57BL/KsJ-db/db (dbdb) mice. Mice were divided into five groups: wild-type mice group (WY), dbdb mice group, dbdb mice + Metformin (100 mg/kg) group, dbdb mice + Umb (20, 40 mg/kg) group. Blood glucose regulation was assessed by an oral glucose tolerance test (OGTT). At 28 days after drug administration, blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, including alanine aminotransferase (ALT), aspartate aminotransaminase (AST) and total cholesterol (TC) and triglyceride (TG). Expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and oxidative stress indicators (SOD and MDA) were measured with ELISA kit. The expressions of high-mobility group box 1 (HMGB1), Toll-like receptor (TLR) 4 (TLR4), Myd88, NF-κB, IκB, Nrf2, and HO-1 proteins were also evaluated by Western blotting analysis. The results showed that Umb significantly restored the blood glucose in OGTT, and inhibited the levels of insulin, TG, TC, as well as activities of ALT and AST. Moreover, Umb inhibited diabetic inflammation through down-regulating the expression of HMGB1, TLR4, NF-κB, and IκB. In addition, Umb alleviated oxidative damage in the liver by activating Nrf2-mediated signal pathway. These findings demonstrated that Umb exhibited protective effect against diabetic live injury, which may be through inhibiting HMGB1-induced inflammatory response and activating Nrf2-mediated antioxidant.
本研究旨在探讨伞形酮（Umb）对糖尿病 C57BL/KsJ-db/db（dbdb）小鼠肝损伤的保护作用及其可能机制。将小鼠分为五组：野生型小鼠组（WY）、dbdb 小鼠组、dbdb 小鼠+二甲双胍（100mg/kg）组、dbdb 小鼠+Umb（20、40mg/kg）组。通过口服葡萄糖耐量试验（OGTT）评估血糖调节情况。给药 28 天后，采集血样分析与肝功能相关的血脂和酶，包括丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆固醇（TC）和甘油三酯（TG）。采用 ELISA 试剂盒测定炎症细胞因子（TNF-α、IL-1β 和 IL-6）和氧化应激指标（SOD 和 MDA）的表达水平。还通过 Western 印迹分析评估高迁移率族蛋白 B1（HMGB1）、Toll 样受体 4（TLR4）、髓样分化因子 88（Myd88）、核因子-κB（NF-κB）、核因子κB 抑制蛋白（IκB）、核因子红细胞 2（Nrf2）和血红素加氧酶 1（HO-1）蛋白的表达。结果表明，Umb 显著恢复了 OGTT 中的血糖，并抑制了胰岛素、TG、TC 以及 ALT 和 AST 的活性。此外，Umb 通过下调 HMGB1、TLR4、NF-κB 和 IκB 的表达抑制了糖尿病炎症。此外，Umb 通过激活 Nrf2 介导的信号通路缓解了肝脏的氧化损伤。这些发现表明，Umb 对糖尿病肝损伤具有保护作用，这可能是通过抑制 HMGB1 诱导的炎症反应和激活 Nrf2 介导的抗氧化作用实现的。
