psoralidin and Sepsis

Myocardial injury is a severe complication of sepsis, resulting in substantial morbidity and mortality. Psoralidin (PSO), derived from the seeds of Psoralea corylifolia L., has garnered considerable attention due to its potent pharmacological effects, including anti-inflammatory and antibacterial effects.. Our previous work conducted affirmed that PSO has a protective effect on sepsis and septic myocardial injury, however the specific molecular mechanisms need further clarification.. This objective of this study was to use three analytic modalities and bioinformatics methods to identify potential targets, followed by experimental verification.. A series of experiments methods (including echocardiography, HE, western blot, qPCR, RNA-seq, network pharmacology) were used to evaluate the effects of PSO against sepsis and septic myocardial injury in cecal ligation and puncture (CLP)-injured BALB/c mice and lipopolysaccharide (LPS)-injured HL-1 cardiomyocytes.. Firstly, a group of sepsis-related genes were identified by integrating database surveys, RNA-seq analysis, and weighted gene co-expression network analysis (WCGNA). Subsequently, the pharmacological targets of PSO were predicted. Furthermore, the identification of phosphoinositide 3- kinase regulatory subunit 5 (PIK3R5) as a crucial hub gene was accomplished via protein-protein interaction network and molecular docking approach. In vivo experiments showed that PSO treatment alleviated septic myocardial injury, as evidenced by improved cardiac function indicators and inflammation response. Similar results were obtained in vitro experiments. Importantly, the expression of PI3KR5 was decreased in the myocardium and cardiomyocytes, and the effect was reversed by PSO treatment.. This study systematically revealed the key targets of PSO in the treatment of septic myocardial injury. These findings offer valuable insights into disease-drug targets, which have certain clinical significance to exploring disease biomarkers and potential therapeutic targets for septic patients.

Topics: Animals; Humans; Mice; Molecular Docking Simulation; Myocardium; Sepsis; Transcription Factors

Sepsis can cause various organ dysfunction, which heart failure may be associated with significant mortality. Recently, natural plant extracts have gradually attracted people's attention in the clinical treatment of cardiovascular diseases. Psoralidin (PSO) is one of the main bioactive compounds from the seeds of Psoralea corylifolia L and exhibits remarkable protective effects in diseases, including cancer, osteoporosis, and depression. Recently, NR1H3 is one of the emerging nuclear receptors targets for the various drugs. This study first reported the porotective role of PSO in septic myocardial injury, which was mainly attributed to the NR1H3-dependent manner. NR1H3 knockout mice subjected to cecal ligation and puncture (CLP) were used to investigate the involvement of NR1H3 in PSO protection. Our results showed that PSO prominently improved cardiac function, attenuated inflammation, inhibited oxidative stress, improved mitochondrial function, regulated ERS, suppressed apoptosis, and particularly increased NR1H3 and p-AMPK levels. However, NR1H3 knockout reversed the positive role of PSO in septic mice. Furthermore, activation of NR1H3 by T0901317 also increased the activity of AMPK and ACC in the HL-1 cardiomyocytes, indicating the regulatory relationship between NR1H3 and AMPK signaling. Together, this study demonstrated the beneficial effect of PSO in septic myocardial injury through activation of NR1H3/AMPK pathway.

Topics: AMP-Activated Protein Kinases; Animals; Heart Injuries; Mice; Mice, Knockout; Myocardium; Sepsis; Signal Transduction