Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways

作者：Meiling Shi, Hong Kan, Yijia Tang, Lanshi Tian, Xiangjuan Guo, Weijia Chen, Jianan Geng, Ying Zong, Yunfeng Bi, Zhongmei He · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms26104838 · 被引用次数：8 · 研究领域：Cancer-related cognitive impairment studies、Medicinal Plant Pharmacodynamics Research、MicroRNA in disease regulation

Chemotherapy-induced renal encephalopathy (RE) is a disease characterized by cognitive impairment of the brain caused by impaired kidney function for which there is no definitive treatment. Icariin (ICA), the main active component of Epimedium, has a good nervous system protection and anti-neuroinflammation effect, but its effect on the brain injury caused by renal insufficiency as a result of chemotherapy remains unclear. In this study, we demonstrated that 100 mg/kg ICA can not only successfully interface with serotonin and regulate hormone levels but also ameliorates kidney damage and cognitive impairment in cyclophosphamide (CTX)-induced RE mouse models and inhibits inflammation, oxidation, and apoptosis by regulating NF-κB, keap1-Nrf2, and apoptosis pathways. In order to further study the protective effect of ICA on RE, we used CTX-induced HT22 and HEK293 cell injury models, and the ICA intervention showed that ICA could prevent apoptosis by regulating the expression of the apoptosis-related proteins caspase-3, Bcl-2, Bax and BDNF. Overall, our study provides a basis for further investigation of the therapeutic potential of ICA in the treatment of neurodegenerative diseases in the context of renal dysfunction, and further studies are needed at a later stage to fully elucidate the underlying molecular mechanisms.