Qiju Dihuang Pill protects the lens epithelial cells via alleviating cuproptosis in diabetic cataract

• Published in: Journal of ethnopharmacology 2024-10, Vol.333, p.118444, Article 118444
• Main Authors: Yang, Jun, Gao, Yichen, Mao, Han, Kuang, Xinqi, Tian, Fang
• Format: Article
• Language: English
• Subjects: Cuproptosis; Diabetic cataract; Diabeties mellitus; Qiju Dihuang Pill; SLC31A1
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118444

Qiju Dihuang Pill (QDP) is a traditional Chinese medicine prescription for the treatment of eye diseases. Novel literature reports that copper-induced cell death, called as cuproptosis, is a copper-dependent and differs distinctly from other types of cell death. The present study aims to investigate whether QDP could protect lens epithelial cells via alleviating copper-induced death in diabetic cataract. The different concentration of QDP medicated serum was administrated on high glucose (HG)-induced human lens epithelial cells (HLECs). The copper concentration was tested using Elabscience Copper Assay kit. The proliferation was detected using CCK-8 and EdU assays. The molecular binding was identified using RIP-PCR and luciferase reporter assay. Results indicated that HG culture condition triggered the copper concentration and repressed the proliferation of HLECs. Then, the elesclomol-Cu (Es–Cu) administration up-regulated the copper concentration and inhibited the proliferation, and cuproptosis inhibitor tetrathiomolybdate (TTM) could specifically reverse the consequence. QDP treatment reduced the copper concentration and cuproptosis-related genes (SLC31A1, FDX1). MeRIP-Seq and RIP-PCR confirmed that QDP reduced the stability of SLC31A1 mRNA through m6A modified site, and copper actually synergized the molecular binding efficiency. Rescue assay verified the role of QDP and SLC31A1 on HLECs’ cuproptosis characteristic. This research identified the protective role of QDP on HG-induced HLECs in DC through decreasing m6A/SLC31A1-mediated cuproptosis in DC. This finding provides novel insights into mechanisms for QDP and sheds light on the multifaceted role of traditional prescription on DC. [Display omitted] •HG culture condition triggered the copper concentration and repressed the proliferation of HLECs.•The elesclomol-Cu administration up-regulated the copper concentration and inhibited the proliferation, and TTM could specifically reverse the consequence.•QDP treatment reduced the copper concentration and cuproptosis-related genes (SLC31A1, FDX1).•QDP reduced the stability of SLC31A1 mRNA through m6A modified site, and copper actually synergized the molecular binding efficiency.•Rescue assay verified the role of QDP and SLC31A1 on HLECs' cuproptosis characteristic.