Uncovering the molecular mechanisms of Curcumae Rhizoma against myocardial fibrosis using network pharmacology and experimental validation

Abstract

Ethnopharmacological relevance: Myocardial fibrosis leads to cardiac remodeling and dysfunction. Curcumae Rhizoma has been utilized in clinical trials to treat a variety of cardiovascular illnesses, although its role in myocardial fibrosis is unknown.

Aim of the study: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with Curcumae Rhizoma.

Materials and methods: The chemical components in the aqueous extract from Curcumae Rhizoma were identified using GC-MS analysis. A prediction network describing the relationship between Curcumae Rhizoma and MF was established based on information collected from multiple databases. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate Curcumae Rhizoma targets acting on MF, which were further validated by vivo experiments.

Results: There were 444 targets obtained from the 39 active ingredients in Curcumae Rhizoma, and 5691 disease targets related to MF were identified. Then, 41 key targets were determined with the PPI interaction network, which was structured from 324 overlapping gene targets. GO and KEGG analyses revealed that the p38 MAPK/NF-κB and TGF-β1/Smad2/3 signaling pathways might play crucial roles in the therapeutic mechanism of MF. According to the results of molecular docking, the binding activity between core components and targets was marvelous (affinity < -6 kcal/mol). Take it a step further, the experimental validation data affirmed that Curcumae Rhizoma substantially decreased myocardial fibrosis and recovered cardiac function in the ISO-induced rats. The associated proteins expression data implied that the p38 MAPK/NF-κB and TGF-β1/Smad2/3 pathways might be vital in the anti-fibrosis effect of Curcumae Rhizoma.

Conclusion: The findings suggested that Curcumae Rhizoma diminished myocardial fibrosis by suppressing fibrosis multiplication and collagen deposition through inhibiting p38 MAPK/NF-κB and TGF-β1/Smad2/3 pathways, which might be a promising therapeutic medicament for alleviating myocardial fibrosis.

Keywords: Curcumae rhizoma; Myocardial fibrosis; NF-κB; Network pharmacology; TGF-β.