Exploring the potential molecular targets and therapeutic mechanisms of Cyperi Rhizoma in treating diabetic cardiomyopathy: a computational approach

Abstract

Diabetic cardiomyopathy (DCM) is a major contributor to heart failure in diabetic patients, characterized by complex pathophysiological mechanisms and a lack of effective targeted therapies. Cyperi Rhizoma (CR), a traditional Chinese medicinal herb, has shown potential in regulating Qi and improving metabolic disorders, yet its therapeutic mechanisms in DCM remain unclear. This study systematically explored the bioactive components and underlying mechanisms of CR in the treatment of DCM by integrating network pharmacology, molecular docking, molecular dynamics simulation (MDS), and in vitro experiments. Active compounds of CR were identified, and DCM-related targets were obtained from GEO, DisGeNET, OMIM, and GeneCards databases. Quercetin, luteolin, and patchoulenone were identified as key compounds, while AKT1, IL6, TNF, IL1B, and TP53 emerged as core targets. Functional enrichment analysis indicated that the AGE-RAGE and TNF signaling pathways may play critical roles in the protective effects of CR against DCM. Molecular docking and MDS demonstrated a stable binding interaction between luteolin and AKT1. Furthermore, in vitro validation confirmed the protective effect of luteolin against high glucose and palmitic acid-induced injury in H9c2 cardiomyocytes. Collectively, this study elucidates the multi-level pharmacological basis and molecular mechanisms of CR in mitigating DCM, providing a theoretical and experimental foundation for its potential therapeutic application.