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Tumor Discovery Mechanism of Buddleja officinalis against ESCC

1. Introduction 2. Materials and methods

The incidence of esophageal cancer (EC), one of the 2.1. Identification of dominant ingredients in BO
most common malignancies worldwide, has dramatically The dominant ingredients of BO were determined from
increased over the past 30 years, especially in developed the TCM systematic pharmacology database (TCMSP,
countries. The primary pathological variants of EC http://tcmspw.com/tcmsp.php) and HERB database
1-3
are esophageal squamous cell carcinoma (ESCC) and (http://herb.ac.cn). The parameters were set as follows: oral
adenocarcinoma, of which ESCC accounts for the vast bioavailability (OB) ≥30% and drug-likeness ≥0.18.
4,5
majority (90%) of the EC cases. Although various factors
have been identified to contribute to the development of 2.2. Establishment of BO active component
ESCC, the specific molecular mechanism of the disease database
remains elusive. Since obvious symptoms are hardly
discoverable in the early stage, most of the ESCC cases are The targets were identified from the PharmMapper
usually diagnosed at an advanced stage, prompting the database (http://www.lilab-ecust.cn/pharmmapper/).
6,7
urgent need for effective treatments. The species in the PharmMapper database was set as
“Homo sapiens” and filtered by ≥0.6 of the norm fit. The
Buddleja officinalis (BO) is an indigenous traditional BO-associated targets were converted to standardized
Chinese medicine (TCM) used in traditional formulations names shown in the UniProt database (https://www.
to treat inflammation, vascular disease, conjunctivitis, uniprot.org/), with the status set to “reviewed” and the
headache, and stroke. 8-10 For example, some studies have species set to “human.”
extensively reported the pharmacologic profiles and
usage of BO in traditional recipes and demonstrated that 2.3. Identification of ESCC-associated targets
flavonoids in BO flower buds possess anti-inflammatory The search term “esophageal squamous cell carcinoma”
and antioxidant activities. In addition, aqueous was used to acquire ESCC-related targets in GeneCards
11
extracts of BO can inhibit high glucose-induced matrix (https://www.genecards.org/) and DisGeNET (https://
metalloproteinase activity in human umbilical vein www.disgenet.org/home/).
endothelial cells. Given that TCM plays a regulatory and
9
synergistic role systematically through multi-target and 2.4. Determination of BO-ESCC shared targets
multi-channel intervention strategies, it holds distinct After obtaining BO component targets (phammapper:
advantages in terms of prevention and personalized http://www.lilab-ecust.cn/pharmmapper/), Venny 2.1
treatment of ESCC. Nevertheless, the underlying (https://bioinfogp.cnb.csic.es/tools/venny/index.html) was
mechanism by which BO exerts its effects on ESCC used to determine the common target of disease and active
remains obscure. ingredients.
Network pharmacology integrates multiple disciplines
to establish network relationships between drugs, targets, 2.5. Establishing the BO-ESCC protein-protein
and diseases, expanding the study of drugs from single- interaction (PPI) network
target research to the entire biological network, thus The PPI network for BO-ESCC shared targets was
providing a more comprehensive understanding of drug constructed using the interaction database platform
mechanisms. This field can assist in discovering new STRING v11.0 (https://cn.string-db.org/). The parameters
drug candidates, optimizing drug design, and predicting are set as follows: the species was set to “Homo sapiens,”
drug efficacy. 12,13 The research methodology of network with the 0.4 of confidence score cutoff.
pharmacology conforms to the basic requirements of the
holistic view of TCM, providing novel ideas and methods 2.6. Visualization of network analysis results
for TCM research. 14-16 The determined BO-ESCC targets were further
Herein, we used the approach of network pharmacology visualized using Cytoscape v3.9.1, and the network
to investigate primary bioactive constituents, targets, analysis plugin was utilized in the software, employing
and putative mechanisms of BO in inhibiting ESCC. The its statistical nodes to analyze the core targets within the
research flowchart is presented in Figure 1. network.

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/td.2312