Mitigation of myocardial ischemia/reperfusion-induced chronic heart failure via Shexiang Baoxin Pill-mediated regulation of the S1PR1 signaling pathway.

BACKGROUND: Well-defined and effective pharmacological interventions for clinical management of myocardial ischemia/reperfusion (MI/R) injury are currently unavailable. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine Previous research on SBP has been confined to single-target treatments for MI/R injury, lacking a comprehensive examination of various aspects of MI/R injury and a thorough exploration of its underlying mechanisms. PURPOSE: This study aimed to investigate the therapeutic potential of SBP for MI/R injury and its preventive effects on consequent chronic heart failure (CHF). Furthermore, we elucidated the specific mechanisms involved, contributing valuable insights into the potential pharmacological interventions for the clinical treatment of MI/R injury. METHODS: We conducted a comprehensive identification of SBP components using high-performance liquid chromatography. Subsequently, we performed a network pharmacology analysis based on the identification results, elucidating the key genes influenced by SBP. Thereafter, through bioinformatics analysis of the key genes and validation through mRNA and protein assays, we ultimately determined the centralized upstream targets. Lastly, we conducted in vitro experiments using myocardial and endothelial cells to elucidate and validate potential underlying mechanisms. RESULTS: SBP can effectively mitigate cell apoptosis, oxidative stress, and inflammation, as well as promote vascular regeneration following MI/R, resulting in improved cardiac function and reduced CHF risk. Mechanistically, SBP treatment upregulates sphingosine-1-phosphate receptor 1 (S1PR1) expression and activates the S1PR1 signaling pathway, thereby regulating the expression of key molecules, including phosphorylated Protein Kinase B (AKT), phosphorylated signal transducer and activator of transcription 3, epidermal growth factor receptor, vascular endothelial growth factor A, tumor necrosis factor-α, and p53. CONCLUSION: This study elucidated the protective role of SBP in MI/R injury and its potential to reduce the risk of CHF. Furthermore, by integrating downstream effector proteins affected by SBP, this research identified the upstream effector protein S1PR1, enhancing our understanding of the pharmacological characteristics and mechanisms of action of SBP. The significance of this study lies in providing compelling evidence for the use of SBP as a traditional Chinese medicine for MI/R injury and consequent CHF prevention.

Effects of omega-3 polyunsaturated fatty acids supplementation for patients with cardiovascular disease risks: a dose-response meta-analysis.

BACKGROUND: Previous studies assessing the impact of omega-3 polyunsaturated fatty acids (ω-3 PUFA) have shown conflicting results in regard to the cardiovascular mortality. It is likely that higher dose of ω-3 PUFA would have a greater effect on the major adverse cardiovascular events (MACEs). Therefore, we performed a dose-response meta-analysis to explore the potential protective effect of ω-3 PUFA, with the increase of daily intake and extension of the intervention period, on patients with cardiovascular disease risks. Outcomes included major adverse cardiovascular events, cardiovascular and all-cause mortality. METHODS: A systematic literature search of PubMed, Embase and the Cochrane Library from inception to September 31, 2019 was conducted to identify the randomized controlled trails (RCTs) of ω-3 PUFA supplementation, which reported cardiovascular events or deaths and recruited no less than 500 participants. We evaluated the effect of ω-3 PUFA through the pooled relative risks (RR) and 95% confidence intervals (95% CI), and further carried out subgroup analysis and dose-response meta-analysis. RESULTS: Fourteen trials including 87718 individuals were reviewed. By conventional statistical significance, there was no apparent difference between the two groups on major adverse cardiovascular effects (RR 0.94, 95% CI 0.84-1.04) and all-cause mortality (RR 0.96, 95% CI 0.91-1.00), but there was an effect on the cardiovascular mortality (RR 0.93, 95% CI 0.88-0.99). However, with the dose increased and intervention period prolonged (daily dose × intervention period > 8 grams/day × years), subgroup analyses showed a more obvious reduction of MACEs (RR 0.79, 95% CI 0.65-0.95) and all-cause mortality (RR 0.93, 95% CI 0.85-1.03). Furthermore, the dose-response meta-analysis presented a 13.05% reduction of MACEs and 8.99% reduction of all-cause mortality with 10 grams/day × years increments. CONCLUSIONS: Updated with the newly published RCTs, this meta-analysis indicated that large dose and long period of interventions with ω-3 PUFA supplementation produce a close association with MACEs and cardiovascular or all-cause mortality. A dose-response beneficial effect was preliminarily established.

Therapeutic effects of Qishen Yiqi Dropping Pill on myocardial injury induced by chronic hypoxia in rats.

The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley (SD) rats were randomly divided into three groups: the control, model, and treatment groups (n = 10 per group). The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill (35 mg·kg(-1)·d(-1)) for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor 1α (HIF-1α) were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1α expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular diseases.