Title:A Network Pharmacology Approach and Validation Experiments to
Investigate the Mechanism of Wen-Dan Decoction in the Treatment of
SINFH
Volume: 27
Issue: 11
Author(s): Baochuang Qi, Minzheng Guo, Xiangwen Shi, Mingjun Li, Yipeng Wu, Yi Wang, Qian Lv, Xinyu Fan, Chuan Li*Yongqing Xu*
Affiliation:
- Department of Orthopedics,
920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Kunming, 650032,
Yunnan, China
- Department of Orthopedics,
920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Kunming, 650032,
Yunnan, China
Keywords:
Wen-dan decoction, steroid-induced necrosis of the femoral head, network pharmacology, traditional Chinese medicine, target identification, GO.
Abstract:
Introduction: Steroid-induced necrosis of the femoral head (SINFH) is a femoral
head necrotic disease caused by prolonged use of hormones. Wen-Dan decoction is used in
Chinese clinical practice for the treatment of steroid-induced necrosis of the femoral head
(SINFH). However, the mechanism and active compounds of Wen-Dan decoction used to treat
SINFH are not well understood.
Objectives: We studied the mechanism of action of Wen-Dan decoction in treating steroidinduced
necrosis of the femoral head (SINFH) via network pharmacology and in vivo experiments.
Methods: The active compounds of Wen-Dan decoction and SINFH-related target genes were
identified through public databases. Then, network pharmacological analysis was conducted to
explore the potential key active compounds, core targets and biological processes of Wen-Dan
decoction in SINFH. The potential mechanisms of Wen-Dan decoction in SINFH obtained by
network pharmacology were validated through in vivo experiments.
Results: We identified 608 DEGs (differentially expressed genes) (230 upregulated, 378 downregulated)
in SINFH. GO analysis revealed that the SINFH-related genes were mainly involved
in neutrophil activation and the immune response. KEGG (Kyoto Encyclopedia of Genes and
Genomes) pathway analysis showed that the SINFH-related genes were mainly associated with
cytokine receptor interactions, lipids, atherosclerosis, and tuberculosis. We identified 147 active
ingredients of Wen-Dan decoction; the core ingredient was quercetin, and licorice was an active
ingredient. Moreover, 277 target genes in the treatment of SINFH with Wen-Dan decoction
were identified, and NCF1, PTGS2, and RUNX2 were selected as core target genes. QRT-PCR
of peripheral blood from SINFH patients showed higher levels of PGTS2 and NCF1 and
showed lower levels of RUNX2 compared to controls. QRT-PCR analysis of peripheral blood
and femoral bone tissue from a mouse model of SINFH showed higher levels of PGTS2 and
NCF1 and lower levels of RUNX2 in the experimental animals than the controls, which was
consistent with the bioinformatics results. HE, immunohistochemistry, and TUNEL staining
confirmed a significant reduction in hormone-induced femoral head necrosis in the quercetintreated
mice. HE, immunohistochemistry, and TUNEL staining confirmed significant improvement
in hormone-induced femoral head necrosis in the quercetin-treated mice.
Conclusion: We provide new insights into the genes and related pathways involved in SINFH
and report that PTGS2, RUNX2, and NCF1 are potential drug targets. Quercetin improved
SINFH by promoting osteogenesis and inhibiting apoptosis.
