Qi Huang Granules Attenuate Sodium Iodate-Induced Retinal Injury and Inflammation via Regulation of Mitochondrial Dynamics Homeostasis.
TL;DR
Findings demonstrate that QHG can ameliorate retinal morphology and ultrastructural damage in mitochondria, such as cellular mitochondria, improve mitochondrial function, and attenuate retinal inflammation, thereby exerting a protective effect against NaIO₃-induced retinal injury.
Abstract
Qi Huang Granules (QHG), a traditional Chinese medicine (TCM) formulation, have been applied clinically for over two decades to treat dry age-related macular degeneration (AMD) and associated fundus lesions. Although its retinoprotective effects have been documented, the associated underlying mechanisms are largely unexplored. The present work focused on investigating the therapeutic efficacy of QHG in sodium iodate (NaIO₃)-induced retinal damage, with a particular focus on how the formula regulated the interaction between inflammatory responses and imbalances in mitochondrial dynamics. UPLC-HRMS, network pharmacology, and molecular docking analyses were integrated for identifying mitochondria-associated bioactive constituents and potential targets of QHG. In the experimental model, retinal injury was induced in rats through tail vein injection of NaIO3. Retinal morphological and ultrastructural changes were assessed by HE staining and transmission electron microscopy. To assess mitochondrial function, mitochondrial membrane potential, mtROS levels, and mtDNA integrity were measured. Additionally, ELISA was performed to quantify IL-1β and IL-18 levels. Key marker levels, including p-DRP1, DRP1, OPA1, MFN2, and NLRP3, were determined by Western blotting, IHC, and qRT-PCR. DNM1L (encoding DRP1) and MFN2 were identified as the primary targets of QHG through UPLC-HRMS and computational analyses. In vivo experimental results showed that treatment with QHG alleviated morphological alterations and ultrastructural damage to the retina and mitochondria in model rats. Furthermore, QHG treatment increased mitochondrial membrane potential, reduced mtROS levels, mitigated mtDNA damage, and reduced IL-1β and IL-18 contents. Mechanistically, QHG downregulated p-DRP1, DRP1, and NLRP3, while upregulating MFN2 and OPA1. Collectively, these findings demonstrate that QHG can ameliorate retinal morphology and ultrastructural damage in mitochondria, such as cellular mitochondria, improve mitochondrial function, and attenuate retinal inflammation, thereby exerting a protective effect against NaIO₃-induced retinal injury. The underlying mechanism may involve the mitochondrial dynamics-NLRP3 pathway.