School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China; Nanjing Institute of Product Quality Inspection, Jiangsu, Nanjing, 210000, PR China.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China.
Biomed Pharmacother. 2019 Sep;117:109088. doi: 10.1016/j.biopha.2019.109088. Epub 2019 Jun 12.
The acute kidney injury(AKI) caused by nephrotoxic drugs contributes to inflammation and oxidative injury in podocytes. Wedelolactone (WED), a natural compound, is found with activities as anti-inflammation, anti-oxidative, anti-free radical,and etc. In this present study, MPC-5 cells were exposed to the nephrotoxic drugs doxorubicin (DOX). The results showed that WED significantly increased the SOD activity, CAT and GSH-Px levels, while significantly decreased the MDA content and ROS levels in DOX-induced MPC-5 cells. WED could also significantly decrease the levels of cytokines IL-6, MCP-1, TNF-α, and TGF-β1. Additionally, the activation and phosphorylation of IκKα, IκBα and NF-κB p65 was inhibited by WED. The co-treatment of PDTC (NF-κB inhibitor) and WED significantly reduced NF-κB p65 phosphorylation. These findings suggested that WED alleviated inflammation and oxidative stress of doxorubicin-induced MPC-5 cells through IκK/IκB/NF-κB signaling pathway.
肾毒性药物引起的急性肾损伤(AKI)导致足细胞发生炎症和氧化损伤。韦德尔内酯(WED)是一种天然化合物，具有抗炎、抗氧化、抗自由基等作用。在本研究中，MPC-5 细胞暴露于肾毒性药物阿霉素(DOX)中。结果表明，WED 显著增加了 DOX 诱导的 MPC-5 细胞中超氧化物歧化酶(SOD)活性、CAT 和 GSH-Px 水平，同时显著降低了 MDA 含量和 ROS 水平。WED 还可以显著降低细胞因子 IL-6、MCP-1、TNF-α和 TGF-β1 的水平。此外，WED 抑制了 IκKα、IκBα 和 NF-κB p65 的激活和磷酸化。用 NF-κB 抑制剂 PDTC 和 WED 共同处理可显著降低 NF-κB p65 的磷酸化。这些结果表明，WED 通过 IKK/IkB/NF-κB 信号通路减轻了 DOX 诱导的 MPC-5 细胞的炎症和氧化应激。
