Lycium barbarum alleviates oxidative stress-induced ferroptosis and enhances mitophagy in intervertebral disc degeneration

Abstract

Lycium barbarum is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. The therapeutic effect of Lycium barbarum on intervertebral disc degeneration (IVDD) has not been conclusively established. In our study, we investigated the mechanisms of Lycium barbarum extract (LBE) using Network pharmacology and bioinformatic analyses. In vitro experiments, the levels of ferroptosis were assessed using Western blot analysis and detection kits for MDA, Ferric iron and GSH. Transmission electron microscopy and Mitotracker were used to detect mitochondrial morphology. Immunofluorescence and Western blot were employed to detect the levels of mitophagy and lysosomal permeability. In vivo experiments, X-ray imaging, morphological staining, and immunohistochemical staining were used to assess the degree of intervertebral disc degeneration. As a result of the intersection between target genes of complex compounds and disease-related genes, 61 overlapping genes were identified, with PTGS2 ranking as the top overlapping gene. Molecular docking revealed that six compounds were highly stable in the Cys41 active site pocket of PTGS2. Moreover, LBE exhibited potential therapeutic effects through inhibiting mitochondrial dysfunction and ferroptosis. Besides, LBE can reduce lysosomal membrane permeability and enhance mitophagy caused by oxidative stress via regulating phosphatidylinositol metabolism. The administration of LBE in vivo can effectively slow the progression of intervertebral disc degeneration. The findings of this study suggest that LBE exhibits maybe a potential therapeutic candidate for intervertebral disc degeneration.