Article title: Impact of Qi-Invigorating Traditional Chinese Medicines on Diffuse Large B Cell Lymphoma Based on Network Pharmacology and Experimental Validation
Journal: Frontiers in Pharmacology
Background: It has been verified that deficiency of Qi, a fundamental substance supporting daily activities according to the Traditional Chinese Medicine theory, is an important symptom of cancer. Qi-invigorating herbs can inhibit cancer development through promoting apoptosis and improving cancer microenvironment. In this study, we explored the potential mechanisms of Qi-invigorating herbs in diffuse large B cell lymphoma (DLBCL) through network pharmacology and in vitro experiment.
Methods: Active ingredients of Qi-invigorating herbs were predicted from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets were obtained via the SwissTargetPrediction and STITCH databases. Target genes of DLBCL were obtained through the PubMed, the gene-disease associations and the Malacards databases. Overlapping genes between DLBCL and each Qi-invigorating herb were collected. Hub genes were subsequently screened via Cytoscape. The Gene Ontology and pathway enrichment analyses were performed using the DAVID database. Molecular docking was performed among active ingredients and hub genes. Hub genes linked with survival and tumor microenvironment were analyzed through the GEPIA 2.0 and TIMER 2.0 databases, respectively. Additionally, in vitro experiment was performed to verify the roles of common hub genes.
Results: Through data mining, 14, 4, 22, 22, 35, 2, 36 genes were filtered as targets of Ginseng Radix et Rhizoma, Panacis Quinquefolii Radix, Codonopsis Radix, Pseudostellariae Radix, Astragali Radix, Dioscoreae Rhizoma, Glycyrrhizae Radix et Rhizoma for DLBCL treatment, respectively. Then besides Panacis Quinquefolii Radix and Dioscoreae Rhizoma, 1,14, 10, 14,13 hub genes were selected, respectively. Molecular docking studies indicated that active ingredients could stably bind to the pockets of hub proteins. CASP3, CDK1, AKT1 and MAPK3 were predicted as common hub genes. However, through experimental verification, only CASP3 was considered as the common target of Qi-invigorating herbs on DLBCL apoptosis. Furthermore, the TIMER2.0 database showed that Qi-invigorating herbs might act on DLBCL microenvironment through their target genes. Tumor-associated neutrophils may be main target cells of DLBCL treated by Qi-invigorating herbs.
Conclusion: Our results support the effects of Qi-invigorating herbs on DLBCL. Hub genes and immune infiltrating cells provided the molecular basis for each Qi-invigorating herb acting on DLBCL.
IGURE 1. A Venn diagram for common hub genes. The red part represents Codonopsis Radix; the green part represents Ginseng Radix et Rhizoma; the yellow part represents Glycyrrhizae Radix et Rhizoma; the brown part represents Pseudostellariae Radix; the blue part represents Astragali Radix.
In a word, this study systematically explored the active ingredients, potential targets, hub genes and the impact of immune cells in Qi-invigorating herbs for DLBCL treatment. Hub genes and immune infiltrating cells provided the molecular basis for each Qi-invigorating herb acting on DLBCL. Study on common mechanisms revealed that CASP3 might be the common target of Qi-invigorating herbs on DLBCL apoptosis. Tumor-associated neutrophils may be main target cells of DLBCL treated by Qi-invigorating herbs. Although this study provided preliminary predictions, it was important for the modernization of TCM. Such researches would undoubtedly increase our understanding of DLBCL pathogenesis. However, the conclusions still need to be verified with subsequent wet lab experiments.
Huang Q, Lin J, Huang S, Shen J. Impact of Qi-Invigorating Traditional Chinese Medicines on Diffuse Large B Cell Lymphoma Based on Network Pharmacology and Experimental Validation. Front Pharmacol. 2021 Dec 9;12:787816. doi: 10.3389/fphar.2021.787816. https://www.frontiersin.org/articles/10.3389/fphar.2021.787816/full