Investigation of the mechanism of Isobavachalcone in treating rheumatoid arthritis through a combination strategy of network pharmacology and experimental verification

This study aimed at investigating the therapeutic efficacy and mechanism of IBC in treating RA through a combined strategy of network pharmacology, in vitro, and in vivo evaluation. Materials and

In short, this study explored the effect of IBC by combining network pharmacology prediction with in vitro and in vivo experimentation. The results indicated that IBC exerts its anti-rheumatoid arthritis effect by regulating cell proliferation and survival via PI3K/AKT and JAK/STAT signaling pathways. This may open a new horizon and provide a theoretical foundation for further development and utilization of IBC in RA management.

The Swiss Target Prediction and GeneCards databases were consulted to predict the potential targets of IBC and RA. Additionally, the potential targets for IBC in treating RA were predicted by consulting databases such as String, Cytoscape, MCODE, and Cytohubba. R software was utilized for enrichment analysis of GO and KEGG pathways, followed by in vitro experimentation using cell lines and in vivo experimentation using animals to explore the potential mechanism of IBC in RA treatment.

By integrating the results of network pharmacological analysis, 17 genes were found to be strongly associated with RA, such as TNF, MAPK13, EGFR, PTGS2, MMP3, etc. The enrichment analysis indicated that IBC possessed tremendous therapeutic efficacy in managing RA through PI3K-AKT, rheumatoid arthritis, and TNF signaling pathways. The in vitro experimentation indicated that IBC inhibited the proliferation, migration, and invasion, and promoted apoptosis and inhibition of inflammation of MH7A cell lines stimulated with TNF-α. The IBC might also have an increasing effect on the intracellular ROS and reducing effect on the mitochondrial membrane potential. The western blotting results indicated that IBC markedly inhibited the expression of p-PI3K, p-AKT, p-JAK1, p-STAT3 and SOCS3 proteins in TNF-α stimulated MH7A cells. Furthermore, we found that IBC also significantly reduced paw swelling and arthritis severity in CIA model rats through in vivo animal studies. Conclusions: In short, this study explored the effect of IBC by combining network pharmacology prediction with in vitro and in vivo experimentation. The results indicated that IBC exerts its anti-rheumatoid arthritis effect by regulating cell proliferation and survival via PI3K/AKT and JAK/STAT signaling pathways. This may open a new horizon and provide a theoretical foundation for further development and utilization of IBC in RA management.