Protein network module-based identification of key pharmacological pathways of Curcuma phaeocaulis Val. acting on hepatitis

Ethnopharmacological relevance: Curcuma phaeocaulis Val. (CP), as the vital medicines for blood-breaking and disorder-eliminating, has been widely used for hepatitis with good curative effects. Owing to the complexity of traditional Chinese medicine, the pharmacological mechanism of CP remains unclear. To solve this problem, a protein network module-based approach was proposed in this study. Materials and methods: Firstly, the content of active components of CP was detected based on HPLC-DAD. Then the liver protection of CP on Con A-induced hepatitis was validated via the analysis of serum levels of ALT, AST and LDH and histological findings. Next, the targets of CP components obtained from TCMD database were predicted by STITCH and ChEMBL retrieval. In addition, the protein interaction network (PIN) of CP was constructed by Cytoscape based on protein-protein interaction of targets obtained from STRING database. Following the topological analysis of CP PIN, it showed to exhibit the properties of scale-free, small world, and modularity matched with the property of complex biological networks. Finally, the functional modules were identified by gene ontology enrichment analysis based on Molecular Complex Detection algorithm. Results: The functional modules indicated that the mechanism of CP acting on the hepatitis is significantly associated with NF-kappa B and TGF-beta signaling pathway. More interestingly, curcumin, demethoxycurcumin and bisdemethoxycurcumin were the main active components of CP acting on the hepatitis, which were demonstrated to be associated with the inflammatory process that occurs during the progression of hepatitis. Conclusion: The protein network module-based approach is an efficient way to investigate the pharmacological mechanisms of CP.