Mechanism identification of an herbal decoction for potential treatment of diffuse large B-cell lymphoma using...

Approximately 30-40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease after standard first-line therapy, highlighting the need for new treatment strategies. Traditional Chinese medicine (TCM) decoctions, such as Fuzheng Jiedu decoction (FZJDD), have shown clinical benefits in DLBCL, but the molecular mechanisms remain unclear. This study aimed to explore the mechanisms of FZJDD in the treatment of DLBCL based on network pharmacology and experimental validation. Potential targets of FZJDD and DLBCL-related genes were collected from multiple databases. The intersection genes between the decoction and DLBCL were identified as the potential therapeutic targets. Network topology analysis was used to identify core active compounds and target genes of FZJDD. Functional enrichment analysis was performed to explore the underlying mechanisms. Molecular docking was used to assess the binding affinities between the key compounds and core proteins. In vivo experiments were conducted to evaluate the effects of FZJDD on tumor growth in the DLBCL xenograft model. Western blot analysis was used to validate the expression of the involved proteins. A total of 274 target genes of FZJDD and 340 DLBCL-related genes were identified, resulting in the identification of 128 overlapping genes as potential therapeutic targets. Topological analysis identified quercetin, luteolin, and isorhamnetin as key active components. STAT3 was identified as the core target in the protein-protein interaction network. Functional enrichment analysis indicated significant enrichment in the JAK-STAT signaling pathway. Molecular docking showed strong binding affinities between the key compounds and the JAK2 and STAT3 proteins. In vivo experiments showed that FZJDD significantly inhibited tumor growth in the DLBCL model. Western blot analysis indicated significant reductions in p-JAK2/JAK2 and p-STAT3/STAT3 ratios in the FZJDD-treated groups compared to controls, with stronger inhibition at higher FZJDD concentrations. This study integrated network pharmacology and experimental validation to identify the core components and target genes of FZJDD in the treatment of DLBCL. The anti-tumor effects of FZJDD were associated with the inhibition of the JAK2/STAT3 signaling pathway. These findings provide a mechanistic basis for the clinical efficacy of FZJDD and lay a foundation for further development of TCM-based therapies for DLBCL management.