Molecular mechanism of celastrol in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking technology

Background: Network pharmacology uses bioinformatics to broaden our understanding of drug actions and thereby advance drug discovery. Here we apply network pharmacology to generate testable hypotheses about the multi-target mechanism of celastrol against systemic lupus erythematosus (SLE). Methods: We reconstructed drug-target pathways and networks to predict the likely protein targets of celastrol and the main interactions between those targets and the drug. Then we validated our predictions of candidate targets by performing docking studies with celastrol. Results: The results suggest that celastrol acts against SLE by regulating the function of several signaling proteins, such as interleukin 10, tumor necrosis factor, and matrix metalloprotein 9, which regulate signaling pathways involving mitogen-activated protein kinase and tumor necrosis factor as well as apoptosis pathways. Celastrol is predicted to affect networks involved mainly in cytokine activity, cytokine receptor binding, receptor ligand activity, receptor regulator activity, and cofactor binding. Molecular docking analysis showed that hydrogen bonding and Tc-Tc stacking were the main forms of interaction. Conclusions: This network pharmacology strategy may be useful for discovery of multi-target drugs against complex diseases, specifically, it provides protein targets associated with SLE that may be further tested for therapeutic potential by celastrol.