Protective effects of triptolide against oxidative stress in retinal pigment epithelium cells via the PI3K/AKT/Nrf2 pathway: a network pharmacological method and experimental validation

作者全名："Pan, Fuying; Shu, Qinxin; Xie, Hao; Zhao, Long; Wu, Ping; Du, Yong; Lu, Jing; He, Yuxia; Wang, Xing; Peng, Hui"

作者地址："[Pan, Fuying; Shu, Qinxin; Xie, Hao; Zhao, Long; Wu, Ping; Du, Yong; Lu, Jing; He, Yuxia; Wang, Xing; Peng, Hui] Chongqing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Pan, Fuying; Shu, Qinxin; Xie, Hao; Zhao, Long; Wu, Ping; Du, Yong; Lu, Jing; He, Yuxia; Wang, Xing; Peng, Hui] Chongqing Key Lab Ophthalmol, Chongqing Eye Inst, Chongqing 400016, Peoples R China"

通信作者："Wang, X; Peng, H (通讯作者)，Chongqing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Wang, X; Peng, H (通讯作者)，Chongqing Key Lab Ophthalmol, Chongqing Eye Inst, Chongqing 400016, Peoples R China."

来源：AGING-US

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001179364200019

JCR分区：Q2

影响因子：5.2

年份：2024

卷号：16

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：triptolide; oxidative stress; PI3K/Akt/Nrf2 pathway; network pharmacological analysis

摘要："Purpose: Among aging adults, age-related macular degeneration (AMD), is a prevalent cause of blindness. Nevertheless, its progression may be halted by antioxidation in retinal pigment epithelium (RPE). The primary effective constituent of Tripterygium wilfordii Hook. F., triptolide (TP), has demonstrated anti-inflammatory, antiproliferative, and antioxidant properties. The mechanics of the protective effect of triptolide against the oxidative damage in retinal pigment epithelial (RPE) were assessed in this study. Methods: ARPE-19 cells were pretreated with TP, and then exposed to sodium iodate (SI). First, cell viability was assessed using CCK-8. Subsequently, we measured indicators for cell oxidation including reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Then, we used network pharmacological analysis and molecular docking to explore the signaling pathway of TP. Last, we used western blot, ELISA, and immunofluorescence assays to clarify the potential mechanistic pathways. Results: The network pharmacology data suggested that TP may inhibit AMD by regulating the PI3K/Akt signaling pathway. Experimental results showed that the potential mechanism is that it regulates the PI3K/Akt pathway and promotes Nrf2 phosphorylation and activation, thereby raising the level of antioxidant factors (HO-1, NQO1) and reducing the generation of ROS, which inhibit oxidative damage. Conclusion: Our findings suggested that the effect of TP on SI-exposed RPE cells principally relies on the regulation of oxidative stress through the PI3K/Akt/Nrf2 signaling pathway."

基金机构：National Natural Science Foundation of China [81670881]

基金资助正文：This study was supported by funds from the National Natural Science Foundation of China (81670881).