Qili Qiangxin capsule attenuates myocardial fibrosis by modulating collagen homeostasis post-infarction in rats.

Myocardial fibrosis (MF) is a major cause of morbidity and mortality worldwide. Qili Qiangxin capsule (QLQX) is a traditional Chinese medicine (TCM) formula used for treating MF, QLQX can affect ventricular remodeling by regulating collagen deposition; however, the specific mechanism by which QLQX modulates collagen homeostasis remains unclear. Thus, this study aimed to explore the effect of QLQX on collagen fibers and its mechanism of action in rats after myocardial infarction (MI). Rats were subjected to left anterior descending artery ligation and then were divided equally into five groups: sham, model, low-dose QLQX, high-dose QLQX and empagliflozin groups. QLQX treatment for 28 days significantly improved cardiac function, as evidenced by decreases in heart mass index, cardiac volume, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, N-terminal B-type natriuretic peptide levels, and high-sensitivity cardiac troponin I levels and increases in left ventricular ejection fraction and left ventricular fraction shortening. Hematoxylin and eosin, Masson, and Picrosirius red staining under a light microscope indicated that QLQX treatment suppressed fibrosis and promoted angiogenesis by decreasing the protein expression levels of proteins related to cardiac remodeling including transforming growth factor-β1, metalloproteinase-9 and α-smooth muscle actin and increasing the expression of tissue inhibitor of matrix metalloproteinase-1 concentration. Picrosirius red staining under the polarized light microscope and western blotting showed that MI increased the contents of collagen I and III, and reduced the contents of collagen II and IV. QLQX treatment improved cardiac function and attenuated MF by modulating collagen homeostasis and promoting angiogenesis. This study provides novel insights into the mechanism of action of QLQX in preventing MF after MI.

Sun M ，Liu C ，Gao K ，Xu X ，Chen K ，Qiu L ，Wang X ... -  《PLoS One》

Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress.

To investigate the pharmacological mechanism of Qili Qiangxin Capsule (QLQX) improvement of heart failure (HF) based on miR133a-endoplasmic reticulum stress (ERS) pathway. A left coronary artery ligation-induced HF after myocardial infarction model was used in this study. Rats were randomly assigned to the sham group, the model group, the QLQX group [0.32 g/(kg·d)], and the captopril group [2.25 mg/(kg·d)], 15 rats per group, followed by 4 weeks of medication. Cardiac function such as left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of increase of left ventricular pressure (+dp/dt max), and the maximal rate of decrease of left ventricular pressure (-dp/dt max) were monitored by echocardiography and hemodynamics. Hematoxylin and eosin (HE) and Masson stainings were used to visualize pathological changes in myocardial tissue. The mRNA expression of miR133a, glucose-regulated protein78 (GRP78), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), X-box binding protein1 (XBP1), C/EBP homologous protein (CHOP) and Caspase 12 were detected by RT-PCR. The protein expression of GRP78, p-IRE1/IRE1 ratio, cleaved-ATF6, XBP1-s (the spliced form of XBP1), CHOP and Caspase 12 were detected by Western blot. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the rate of apoptosis. QLQX significantly improved cardiac function as evidenced by increased EF, FS, LVSP, +dp/dt max, -dp/dt max, and decreased LVEDP (P<0.05, P<0.01). HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent. Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue (P<0.01). Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of miR133a and inhibited the mRNA expressions of GRP78, IRE1, ATF6 and XBP1, as well as decreased the protein expressions of GRP78, cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio (P<0.05, P<0.01). Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12, resulting in a significant reduction in apoptosis rate (P<0.05, P<0.01). The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the miR133a-IRE1/XBP1 pathway.

Ji XD ，Yang D ，Cui XY ，Lou LX ，Nie B ，Zhao JL ，Zhao MJ ，Wu AM ... -  《-》

Qiliqiangxin Attenuates Adverse Cardiac Remodeling after Myocardial Infarction in Ovariectomized Mice via Activation of PPARγ.

This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice. Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice. Masson's Trichrome staining was applied to evaluate myocardial fibrosis. Collagen deposition was determined by the mRNA level of Collagen I, Collagen III and α-SMA using real-time quantitative polymerase chain reaction (qPCR). Myocardial apoptosis was examined by the protein level of Bax, Bcl2 and the Bcl2/Bax ratio using western blotting. These mice displayed a significant reduction in heart function, increased myocardial fibrosis and apoptosis, and decreased expression of peroxisome proliferator activated receptor γ (PPARγ) in the heart tissue, which could be reversed by QLQX treatment. Inhibition of PPAR reduced QLQX-mediated cardio-protective effects, while PPARγ activation did not further enhance the beneficial effect of QLQX. Furthermore, QLQX upregulated 9 genes (Cd36, Fatp, Pdk4, Acadm, Acadl, Acadvl, Cpt1a, Cpt1b and Cpt2) facilitating energy metabolism in the MI hearts of the OVX mice and 5 (Acadm, Acadl, Cpt1a, Cpt1b, Cpt2) of the 9 genes were the downstream targets of PPARγ. The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPARγ, suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.

Shen S ，Jiang H ，Bei Y ，Zhang J ，Zhang H ，Zhu H ，Zhang C ，Yao W ，Wei C ，Shang H ，Li X ... -  《-》

The role of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction rats.

Zhang SX ，Zhuang LL ，Liu J ，Jing YY ，Sun J ，Gong L ，Liu XY ... -  《-》

[Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Heart Failure Rats after Myocardial Infarction and Its Mechanism].

Han AB ，Zhang J ，Zhao MJ ，Zhao YZ ，He YY ，Zhang DD ，Cui XN ... -  《-》