Activation of NR1H3 signaling pathways by psoralidin attenuates septic myocardial injury.

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.

Kudzu Celery Decoction Exerts Protection against Sepsis-Induced Myocardial Injury.

Myocardial dysfunction is well-recognized manifestations of organ dysfunction in sepsis, which is the leading cause of death in critically ill patients. The underlying mechanisms associated with sepsis-induced myocardial injury (SIMI) include cardiac contractility, inflammatory response, oxidative stress, and apoptosis. Kudzu celery decoction (KCD) is composed of a variety of traditional Chinese medicine (TCM) such as kudzu and celery. The previous study found that the main ingredients in kudzu and celery have also been proved to have anti-inflammatory, antioxidative, and other biological activities. In this study, the therapeutic effects of KCD were evaluated in the cecal ligation and puncture (CLP) model of BALB/c mice. The effects of KCD on cardiac function, myocardium damage, inflammation, and fibrosis in CLP-injured mice were analyzed with echocardiography, histological staining, and quantitative real-time PCR. The results showed that KCD treatment improved the anal temperature, sepsis score, blood routine parameters, and blood biochemical parameters in CLP-injured mice. Then, we observed that KCD could remarkably alleviate cardiac dysfunction, myocardial fibrosis, oxidative stress, and inflammation in CLP-injured mice. In this study, we confirmed that KCD has a significant protective effect on SIMI, which may favor KCD a potential cardioprotective drug candidate to alleviate SIMI and further amplify the application of TCM prescription in clinic.