Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression

Ethnopharmacological relevance: The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF). The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro. Materials and methods: The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF. From this, electrocardiographic parameters and exterior signs of rat hearts were recorded. Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured. Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle. Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control. Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-kappa B activity luciferase reporter assay systems. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-kappa B inhibitors from YQFM. Results: The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) in CHF rats. Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed. Among these compounds, ginsenoside Ro was revealed as a new NF-kappa B inhibitor. Conclusion: The results suggested that NF-kappa B inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF. (C) 2013 Elsevier Ireland Ltd. All rights reserved.