Page 279 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology QGJSF multi-target mechanisms in osteoporosis

1. Introduction In the field of TCM research, network pharmacology has
emerged as a novel methodology. By merging techniques
Osteoporosis (OP) is a systemic skeletal disease from systems biology, bioinformatics, and computational
characterized by reduced bone mass and degeneration of chemistry, network pharmacology allows for a holistic
bone microstructure, which significantly increases the risk elucidation of the mechanisms of action of TCM formulas.
of fractures and severely affects patients’ quality of life and Previous studies utilizing network pharmacology have
life expectancy. With the acceleration of global population made progress in deciphering the mechanisms of TCM
aging, OP has become an important public health challenge. compound formulas. However, limitations remain, such as
According to data from the International OP Foundation, limited depth in target-disease association analyses and a
over 200 million people worldwide were affected by lack of comprehensive analysis across multiple databases. 5-7
OP as of 2020, with an OP-induced fracture occurring
approximately every 3 s. Since 1990, the global incidence This study employs integrated network pharmacology
of hip fracture has steadily increased, with projections and bioinformatics approach to systematically investigate
estimating a 240% rise among women and a 310% increase the multidimensional therapeutic mechanism of the
among men by 2050. Furthermore, approximately 50% QGJSF against OP. The active components in QGJSF and
of individuals who experience osteoporotic fractures are their potential targets were identified using the TCMSP
likely to suffer a subsequent fracture. 1,2 and BATMAN-TCM databases, while OP-related targets
Clearly, as the degree of global population aging deepens were retrieved from GeneCards, OMIM, and DisGeNET
further, the incidence of OP has risen to become the third databases. A compound-disease target interaction network
most common chronic disease following cardiovascular was constructed using the bioinformatics platform,
diseases and diabetes, becoming one of the ten important followed by a protein-protein interaction (PPI) network
chronic diseases threatening human health. Traditional through the STRING database. Core therapeutic targets
treatment methods mainly rely on pharmacological were identified through topological analysis through
interventions, such as bisphosphonates and selective Cytoscape. Functional annotation through the DAVID
estrogen receptor modulators. However, these treatments database facilitated comprehensive gene ontology (GO)
come with certain side effects and limitations, including and Kyoto Encyclopedia of Genes and Genomes (KEGG)
gastrointestinal discomfort and kidney damage, especially pathway enrichment analyses, elucidating key biological
with prolonged use. Therefore, the exploration of safe and processes (BP) and signaling pathways involved in the
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effective alternative therapies is essential. anti-osteoporotic effects of QGJSF. Molecular docking
using AutoDock tools validated binding affinities
In recent years, traditional Chinese medicine (TCM) between bioactive components and core targets, while
formulas have received considerable attention for their GEO database-derived clinical data verification and gene
application in preventing and treating OP. Due to their set enrichment analysis (GSEA) further deciphered the
multi-target and multi-level mechanisms of action, TCM has regulatory networks of pivotal genes. Overall, this study
shown unique advantages in improving bone metabolism offers scientific evidence supporting the multi-component,
and enhancing bone density. The Qiang-gu-jian-shen multi-target, multi-pathway mechanisms underlying
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formula (QGJSF) is composed of six medicinal herbs, QGJSF’s therapeutic efficacy against OP and establishes
including Cortex Eucommiae (Du Zhong, DZ), Fructus Lycii an innovative methodological framework for modernizing
(Gou Qi, GQ), Radix Achyranthis Bidentatae (Niu Xi, NX),
Radix Astragali (Huang Qi, HQ), Chuanxiong Rhizoma TCM formulations through systems biology approaches.
(Chuanxiong, CX) and Rehmanniae Radix Praeparata (Shu 2. Materials and methods
Di Huang, SDH), has demonstrated significant efficacy in
clinical treatments for OP. Based on TCM principles that 2.1. Screening for targets related to QGJSF
“the kidneys govern the bones” and “the liver and kidneys Targets associated with QGJSF were identified through
share a common origin,” QGJSF aims to replenish kidneys searches using the TCMSP (https://old.tcmsp-e.com/
and essence, promote blood circulation, resolve stasis, and disease.php?qd=421) and BATMAN-TCM (http://bionet.
strengthen muscles and bones. Although its clinical success, ncpsb.org/batman-tcm/) databases. The identified targets
the specific mechanisms of action underlying QGJSF have were converted using the UniProt database, and duplicate
not been fully elucidated. entries were removed. For TCMSP data, targets were

In recent years, the development of systems biology screened using criteria of oral bioavailability ≥30% and
has brought new perspectives for studying complex drug-likeness ≥0.18. In the BATMAN-TCM database,
diseases by enabling the integration of multi-omics data to screening was based on a score cutoff of 0.84, an adjusted
facilitate a deeper understanding of disease mechanisms. p-value (Benjamin-Hochberg correction) ≤0.05, and

Volume 9 Issue 2 (2025) 271 doi: 10.36922/EJMO025150103