Mechanisms and Molecular Targets of the Tao‐Hong‐Si‐Wu‐Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study

Abstract

The Tao-Hong-Si-Wu-Tang (THSWT) formula, a classic prescription of traditional Chinese medicine, has long been used for the treatment of osteonecrosis of femoral head (ONFH). However, its mechanisms of action and molecular targets are not comprehensively clear. In the present study, the Traditional Chinese Medicine System Pharmacology (TCMSP) database was employed to retrieve the active compounds of each herb included in the THSWT formula. After identifying the drug targets of active compounds and disease targets of ONFH, intersection analysis was conducted to screen out the shared targets. The protein-protein network of the shared targets was built for further topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were then carried out. A gene pathway network was constructed to screen the core target genes. We identified 61 active compounds, 155 drug targets, and 5443 disease targets. However, intersection analysis only screened out 37 shared targets. Kaempferol, luteolin, and baicalein regulated the greatest number of targets associated with ONFH. The THSWT formula may regulate osteocyte function through specific biological processes, including responses to toxic substances and oxidative stress. The regulated pathways included the relaxin, focal adhesion, nuclear factor-κB, toll-like receptor, and AGE/RAGE signaling pathways. RELA, VEGFA, and STAT1 were the important target genes in the gene network associated with the THSWT formula for the treatment of ONFH. Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH.

Exploring the target and signaling pathway of Epimedium in the treatment of steroid-induced avascular necrosis of femoral head based on network pharmacology and molecular docking

“…Quercetin inhibits LPS-induced osteoblast apoptosis, promotes BMSC proliferation, enhances osteoblast differentiation through the MAPK signaling pathway [21][22][23] . Studies have shown that luteolin can exert anti-apoptotic effects through mitochondrial pathways in osteoblasts [24] , and luteolin has been found to have strong anti-inflammatory effects and help inhibit bone resorption induced by mature osteoclasts [25][26][27] . Kaempferol inhibits osteoclasts and promotes osteoblast differentiation [28] .…”

Network-Based Pharmacology and Bioinformatics Study on the Mechanism of Action of Gujiansan in the Treatment of Steroid-Induced Avascular Necrosis of the Femoral Head

“…It is gradually accepted in clinical applications and medical institutes worldwide [7][8][9][10]. Numerous basic and clinical experiments show that compound TCM is economical and has multiplicity and low side effects in treating SANFH [10,11]. Gujiansan is a formula created by Professor Wei Guikang, a master of TCM, based on the theory of traditional Chinese therapeutics and medication as well as his accumulated experience in the past decades.…”