Search

Mudan granules (MuD), a time-honored traditional Chinese patent medicine (TCPM), are widely utilized in the clinical treatment of diabetic peripheral neuropathy (DPN). In the field of biomedical diagnostics, both diabetic retinopathy (DR) and DPN are recognized as critical microvascular complications associated with diabetes. According to the principles of traditional Chinese medicine (TCM), these conditions are primarily attributed to a deficiency in Qi and the obstruction of collaterals. Despite this, the protective effects of MuD on DR and the underlying mechanisms remain to be comprehensively elucidated. The purpose of this study was to investigate the effect of MuD on DR and to further explore the promising therapeutic targets. A diabetic mouse model was established by administering 60 mg/kg of streptozotocin (STZ) via intraperitoneal injection for five consecutive days. The therapeutic efficacy of MuD was evaluated using a comprehensive approach, which included electroretinogram (ERG) analysis, histopathological examination, and assessment of serum biochemical markers. Then, the pharmacodynamic mechanisms of MuD were systematically analyzed using Tandem Mass Tags-based proteomics. Meanwhile, the candidate compounds of MuD were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and molecular docking was applied to estimate the affinity of the active ingredient to their potential key targets. In addition, the functional mechanisms identified through bioinformatics analysis were confirmed by molecular biological methods. We demonstrated that MuD provided significant protection to retinal function and effectively mitigated the reduction in retinal thickness observed in the animal model. Through proteomic analysis, we identified a substantial regulation by MuD of 70 biomarkers associated with diabetic retinal damage. These proteins were notably enriched in the tumor necrosis factor (TNF) signaling pathway, a critical mediator in inflammatory processes. A particularly intriguing finding was the significant downregulation of fibrillin-2 (FBN2) in the diabetic retina compared to the control group (0.36 times the level), and its most pronounced upregulation (3.26 times) in the MuD treatment group. This suggests that FBN2 may play a pivotal role in the protective effects of MuD. Molecular docking analyses have unveiled a robust interplay between the components of MuD and TNF-α. Further corroboration was provided by molecular biological methods, which confirmed that MuD could suppress TNF-mediated inflammation and prevent retinal neovascularization and fibrogenesis. MuD have the potential to alleviate diabetic retinal dysfunction by effectively curbing the fibrogenesis-associated neoangiogenesis and mitigating the inflammatory response, thereby restoring retinal health and function. [Display omitted] • MuD could serve as a promising alternative candidate for DR treatment. • MuD exerts anti-inflammatory, anti-fibrogenic and anti-angiogenic effects on DR. • MuD combats inflammation by inhibiting the TNF-α/NFκB/IL-6 axis. • MuD mitigates fibrosis through modulation of the FBN2/TGF-β1/VEGFA pathway. [ABSTRACT FROM AUTHOR]