iProXProteomicsMing AnRattus Norvegicushttp://www.iprox.org/page/project.html?id=IPX0015616000102009113@btmc.edu.cnBaotou Medical CollegeiProXRenal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.Luo Yiduo Y, Wu Guodong G, Zhao Longshan L, Bo Yukun Y, Yang Dan D, Guo Jingjing J, Zhao Dongdong D, Lv Yanan Y, Tian Yi Y, Wang Mengyang M, Yang Xuemiao X, An Ming MfalseMulti-omics integrative analysis reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation functionRenal 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.Fri Feb 06 00:00:00 GMT 2026PXD0741341011642276167