Work

Catalpol Research on the Mechanism of Antimyocardial Reperfusion Injury by Regulating the MiR-126/TWEAK-FN14 Pathway: In Vitro and Computer Simulation Studies

Year: 2025

Type: article

Abstract: The objective of this study was to investigate the mechanism through which catalpol (CAT) exerts its protective effects in the context of myocardial ischemia-reperfusion injury. Preliminary results showed that Cat significantly attenuated oxygen-glucose deprivation/reoxygenation (OGD/R) damage to H9C2 cells, inhibited intracellular reactive oxygen species levels, and downregulated the protein expression of TWEAK and Fn14 post-OGD/R. The intracellular level of miR-126 was downregulated after OGD/R, and this effect was reversed by CAT administration. To further elucidate its mechanisms, a miR-126 inhibitor was used in the H9C2 cells, and the inhibitory effect was validated using real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Following CAT treatment, lactate dehydrogenase (LDH) levels within the cells were assessed. The results revealed that CAT not only decreased LDH levels but also modulated the miR-126/TWEAK-FN14 signaling axis and the expression of inflammatory-related mediators, as evidenced through RT-PCR and Western blot. Additionally, molecular docking (MD) studies suggested that CAT exhibited a strong binding affinity to both the signaling pathway and inflammatory-related components. Furthermore, molecular dynamics simulations (MDS) demonstrated that the CAT-protein complex exhibited high stability, flexibility, and low binding free energy under physiological conditions. Additionally, CAT showed favorable absorption, distribution, metabolism, excretion, and toxicity characteristics. In summary, this study, through in vitro experimentation, confirmed that CAT regulates the miR-126 and inflammatory proteins within the signaling pathway, with these results being further supported by MD and MDS analyses.

Source: ACS Omega

DOI: 10.1021/acsomega.4c11357

Authors: Ting Wang, Chongyu Shao, Huiyan An, Guanfeng Xu, Haitong Wan, Jiehong Yang

Institutions: Zhejiang Chinese Medical University, Henan University of Traditional Chinese Medicine

Language: English

Topic: Cardiac Ischemia and Reperfusion

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,935