Mechanism of Qiling Fuzheng Qingjie granules in alleviating doxorubicin-induced T cell immune dysfunction via mitochondrial energy metabolism

Abstract This study investigates the mechanism by which Qiling Fuzheng Qingjie Granule (QFQ) regulates immune function following doxorubicin (DOX) chemotherapy. Network pharmacology analysis was employed to explore the relationship between QFQ and the immune system. A mouse model of DOX-induced immune dysfunction was established and treated with QFQ. Techniques including histological staining, peripheral complete blood count analysis, flow cytometry, and seahorse metabolic analysis were used to systematically evaluate the effects of QFQ on immune organs, bone marrow hematopoiesis, T-cell subset distribution and function, mitochondrial metabolism, and antitumor efficacy. The results demonstrated that QFQ significantly alleviated DOX-induced atrophy of the thymus and spleen, preserved bone marrow hematopoietic function, and reduced peripheral blood cell loss. Mechanistically, QFQ improved mitochondrial membrane potential and oxidative phosphorylation, thereby restoring T-cell metabolic capacity, enhancing T-cell activation and proliferation, and restoring cytotoxic T lymphocyte (CTL) function. Consequently, QFQ rebalanced the dynamics among Th1/Th2/Th17/Treg, Effector Memory T/Effector T cells (Tem/Teff), and Central Memory T cells (Tcm) subsets, ameliorated DOX-induced immune dysregulation. In addition, QFQ intervention not only enhanced antitumor efficacy in the A20 lymphoma mouse model but also significantly alleviated the exhaustion phenotype in CD8 + T cells. In summary, this investigation establishes that QFQ enhances T-cell functional performance primarily through the regulation of mitochondrial energy metabolism. By restoring metabolic homeostasis in T lymphocytes, QFQ effectively counteracts DOX-induced immune dysfunction, highlighting its potential as a promising adjunctive therapy in chemotherapy-induced immunosuppression.