Integrating Transcriptomics and Network Pharmacology to Explore the Mechanism of Rhizoma Corydalis in Preventing DOX-Induced Acute myocardial Injury in Mice

Ethnopharmacological relevance Acute myocardial infarction (AMI) significantly increases the global health and economic burden. Although Western drug therapies have successfully reduced mortality in patients with acute myocardial injury, they are not without drawbacks, including a range of adverse effects. Although Rhizoma Corydalis (YHS) has been used in China for over a thousand years to prevent cardiac conditions, its precise preventive and therapeutic effects on AMI areremain unclear, necessitating further research into its mechanisms of action. Aim of the study To assess the therapeutic potential of YHS against AMI, this study seeks to identify its active components and thereby establish its pharmacological basis. Materials and methods In this study, an AMI model was established in mice by tail vein injection of doxorubicin (DOX). Network pharmacology and UHPLC-Q Exactive Orbitrap HRMS technology were used to predict the active constituents, target molecules, and mechanisms of action of YHS against AMI. Echocardiography, histopathological examination, and serum biochemical assays were utilized to assess the therapeutic benefits of YHS and its main active component TP on the AMI mice model. The effects of YHS on the signaling pathways and gene expression profile in AMI were investigated by transcriptome analysis. ROS staining, Western blotting, PCR, and immunofluorescence were utilized to validate the mechanisms of YHS in preventing AMI. Results According to our research, DOX-induced changes in body weight and cardiac indices were considerably improved by both YHS and its main active component TP, which also successfully decreased levels of lactate dehydrogenase (LDH) and creatine kinase MB isoenzyme (CK-MB). YHS and TP significantly improved the low EF and FS levels brought on by DOX overdose, according to echocardiography. Myofibrillar disarray, myocardial cell nuclear atrophy, and inflammatory cell infiltration in the heart were all improved by YHS and TP, according to histological study. The NOD-like receptor pathway, which included important proteins like Nox2, TXNIP, NLRP3, and Caspase-1, may be the basis for YHS's ACT-improving mechanism, according to network pharmacology prediction and transcriptomics research. In addition, DHE staining, immunofluorescence detection, PCR, and Western blot experiments demonstrated that YHS improved AMI in mice by inhibiting DOX-activated Nox2, lowering excessive ROS production, suppressing TXNIP translocation, and reducing inflammasome expression (including NLRP3 and Caspase-1). Conclusion According to research, YHS successfully reduced doxorubicin-induced acute myocardial injury by blocking the NOD-like receptor pathway, lowering levels of reactive oxygen species (ROS) and the important oxidative stress gene Cybb , and decreasing the production of inflammasomes. This work offered fresh perspectives on the pharmacological activities of traditional Chinese medicine in treating AMI from a variety of angles by first revealing the intricate processes by which YHS prevented AMI at the levels of oxidative stress and inflammasome.