Efficacy and Mechanism of Core Traditional Chinese Medicines for Treating Malignant Lymphoma based on Efficacy Studies: A Study Supported by Network Pharmacology and Molecular Docking
Authors: Jin Jiayue , Ren Simeng , Han Baojin , Zhang Wenzheng , Xu Hongkun , Yang Jingqi , Liu Jie 
Published: July 2024

Background:

The burden of malignant lymphoma in China is greater than the global equivalent.
The randomized controlled trials provide medical evidence that TCM can improve the response and survival
in patients with lymphoma. However, the mechanisms underlying remain undefined.

Objective:

Evidence-based data mining for traditional Chinese medicine (TCM) on improving response and
survival in malignant lymphoma treatment was performed in this study. In addition, the mechanisms of TCM
through network pharmacology and molecular docking were explored.

Methods:

The China national knowledge infrastructure, Wanfang Data, China Science and Technology Journal
Database, PubMed, and Web of Science databases were searched to select TCM formulas with response
and survival benefits in the treatment of malignant lymphomas. We then analyzed and visualized the tropism
of taste, frequency of drug use, dosage, clustering, association rules mining (minimum support threshold as
0.20, the minimum confidence threshold as 0.80 and lift >1), and complex networks for potential core herb
compositions using Excel, IBM SPSS Statistics 26, and IBM SPSS Modeler 18. TCM systems pharmacology,
GeneCards, Online Mendelian Inheritance in Man, and other databases were used to screen potential core active
ingredients and malignant lymphoma-related targets. The intersection targets were used to construct a
protein interaction network using Cytoscape to obtain the key targets. Gene Ontology and Kyoto Encyclopedia
of Genes and Genomes pathway enrichment were used to analyze the core target, and molecular docking
of key components and targets was performed using CB-Dock2.

Results:

Twenty-four Chinese herbal formulae were included, encompassing 107 herbs with mainly cold and
warm properties and bitter and sweet flavors. They were associated with the yin meridians of the liver, spleen,
and lungs. The TCMs underwent association rule analysis, identified 27 association rules, including 12 herb
pairs and 13 angle medicine, and clustered into eight classes by clustering analysis. Combined with the results
from mining analysis, Pinelliae (Ban-xia), Poria (Fu-ling), Atractylodis macrocephalae (Bai-zhu), Curcumae
(E-zhu), and Sparganii (San-leng) were the potential core herbs According to network pharmacology and molecular
docking, the main core components of the potential core drugs are hederagenin, cerevisterol, 14-
acetyl-12-senecioyl-2E,8E,10E-atractylentriol, 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid, cavidine,
and baicalein. These core drugs are mainly involved in the pathways of EGFR tyrosine kinase inhibitor resistance,
PD-1/L1, natural killer cell-mediated cytotoxicity, NF-κB, epithelial cell signaling in H. pylori infections,
and Th17 cell differentiation. They aid in regulating the transmembrane receptor protein tyrosine kinase
signaling pathway, ERBB signaling pathway, PI3K signaling pathway, and phosphorylation process. Ten
key components and eight key targets, including baicalein and hederagenin, demonstrated strong binding
activity.

Conclusion:

Collectively, some core herbs exerted anti-tumor effects through immune and inflammatory
pathway modulation, inhibition of immune escape, and induction of cell apoptosis. These findings support future
evidence-based research on malignant lymphoma treatment using TCM.