Discovery the Mechanism of Qingdi Mixture for Radiation-Induced Lung Injury Based on Network Pharmacology, Clinical Retrospective Analysis and Experimental Validation.

Radiation-induced lung injury (RILI) can be caused by thoracic tumor radiotherapy. Qingdi mixture (QDM) has been routinely used in preventing RILI during tumor radiotherapy. However, the molecular mechanisms of QDM remain to be fully elucidated. Initially, we employed network pharmacology to identify potential therapeutic targets and their related signaling pathways. Secondly, molecular docking was applied to validate the interactions between the QDM components and hub targets. Furthermore, we retrospectively collected clinical data from RILI patients who received basic therapy combined with QDM. To investigate the therapeutic potential, we established both in vitro RILI cell models and in vivo murine models. We elucidated the molecular mechanisms of QDM's protective effects against RILI. The network pharmacology results showed that 157 common targets were identified for RILI. Enrichment analysis indicated that NF-κB, JAK-STAT, and necroptosis signaling pathways were involved in the QDM treatment of RILI. The molecular docking results indicated that ligands from multiple compounds exhibited strong interactions with inflammatory cytokines, including IL-6, IL-1α, IL-4, and so on. The therapeutic efficacy of QDM was verified by clinical observation of patients with RILI. In vitro experiments demonstrate that QDM promotes cell proliferation after radiation therapy. Meanwhile, in vivo experiments showed that QDM reduced inflammatory factor levels and enhanced the therapeutic effects of basic treatment. Finally, the western blot experiments were conducted to verify the activation of the NF-κB signaling pathway, as predicted by network pharmacology. This study demonstrated that QDM effectively alleviates RILI and holds promise for broad clinical application.