Multi-omics integrative analysis reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function
Background: Renal fibrosis (RF) is a common pathological process in the progression of chronic kidney disease (CKD) to end-stage renal failure and is also a key target for the prevention and treatment of kidney diseases. It is closely associated with mitochondrial dysfunction, particularly impaired oxidative phosphorylation (OXPHOS). Arctigenin (ATG) is the main active component of burdock seed, with pharmacological effects such as anti-inflammatory, antioxidant, anti-fibrotic, and immunoregulatory activities. However, its key molecular targets and underlying mechanisms in treating RF remain unclear. Objective: To systematically screen the key regulatory targets and core signaling pathways of ATG in intervening RF and provide a molecular basis to clarify its mechanism of action.Study Design: A rat RF model was established by inducing unilateral ureteral obstruction (UUO). The rats were then assigned to sham surgery (Sham), UUO model (Model), and treatment groups (Treat) After 14 days of intervention, kidney tissues were collected. Histopathological changes were evaluated by HE and Masson staining. Integrated transcriptomics and proteomics analyses were used to identify differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) regulated by ATG. . Results: Multi-omics enrichment analysis (GO and KEGG) revealed that the core targets are predominantly enriched in NDUFS8 and NDUFS2, with the OXPHOS pathway being the central intersecting pathway. Conclusion: ATG may exert its anti-RF effects by targeting the OXPHOS signaling pathway to inhibit the excessive production of reactive oxygen species (ROS), mitochondrial energy depletion, and oxidative stress.