QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53 signaling pathway

Abstract

The ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the treatment of heart failure (HF) in China. Previous studies have shown that QSKL has definite effects on HF. The purpose of this study is to identify the regulation of QSKL on apoptosis and clarify the underlying mechanism. An apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery (OGD/R). An animal model of HF was induced by ligation of left anterior descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular ROS generation, increased mitochondrial membrane potential and protected H9C2 cells against OGD/R-induced apoptosis. In vivo results showed that QSKL administration could improve cardiac functions, decrease fibrotic area, infarct size and apoptotic rate in HF model. QSKL regulated the expressions of key apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated the phosphorylated expressions of PI3K and Akt without significantly affecting PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.

Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

“…QSG has been demonstrated to improve myocardial energy metabolism by regulating FA and glucose metabolism in the rat model of HF induced by AMI in this study. In our previous studies, we have established stable injury models of cardiomyocytes and fibroblasts in vitro [15,43]. We will explore the regulatory mechanism of QSG on the energy metabolism of cardiomyocytes and myocardial fibroblasts, and endeavor to find out which compounds in QSG can regulate the targets of myocardial energy metabolism in the future study.…”

“…QSG is a frequently prescribed formula with impressive cardio-protective properties for many years in China [13]. Previous studies reported that QSG could improve microcirculation by exerting anti-inflammatory, anti-apoptosis and anti-fibrosis effects [14][15][16][17][18][19]. In our previous study, mRNA transcriptomic analysis was used to investigate the regulatory pathway of QSG on HF rat model [20].…”

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF‐α–induced injury via inhibiting NF‐κB and JNK signals

“…22,23 In addition, previous studies showed that Lonicerae Japonicae Flos, which was used in traditional Chinese formula, had significant benefits in the treatment of heart failure in clinical as well as animal research. 24,25 The effects of Lonicerae Japonicae Flos may be associated with its major active ingredient chlorogenic acid (5-caffeoylquinic acid, CGA). Earlier studies indicated that CGA has anti-inflammatory, 26 anti-oxidant, 27 anti-apoptotic, 28 analgesic, 29 antihyperalgesic 30 and antidiabetic effects.…”

Antiapoptosis and Antifibrosis Effects of Qishen Granules on Heart Failure Rats via Hippo Pathway

“…Qishen granules (QSG), composed of Radix Astragali, Radix Salvia Miltiorrhizae, Flos Lonicerae, Radix Scrophulariae, Radix Aconiti Lateralis Preparata, and Radix Glycyrrhizae (Table 1), are a famous formula with cardioprotective properties prescribed to HF for many years. e previous studies have demonstrated that QSG could inhibit myocardial inflammation injury, cardiomyocyte apoptosis, and myocardial fibrosis [18][19][20][21] while its underlying mechanism remains to be further defined. Transcriptomics is a potent tool that offers convenient and reliable access to changes in the expression of genes, which could shed light into multiplexed mechanisms of drugs [22].…”