Effect of QSKL on MAPK and RhoA Pathways in a Rat Model of Heart Failure

Abstract

Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery. Cardiac functions were measured by echocardiography and collagen deposition was assessed by Masson staining. Expressions of the key molecules involved in the RhoA and MAPK pathways were also measured. Twenty-one days after surgery, cardiac functions were severely impaired and collagen deposition was remarkable, while QSKL treatment could improve heart functions and alleviate collagen deposition. Further results demonstrated that the effects may be mediated by suppressing expressions of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Moreover, expressions of RhoA, Rho-associated protein kinase 1/2 (ROCK1/2), and phosphorylated myosin light chain (p-MLC) were also downregulated by QSKL compared with the model group. The cardioprotective mechanism of QSKL on heart failure is probably mediated by regulating both the MAPK and RhoA signaling pathways.

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

“…All experimental procedures were conducted according to the National Institute of Health Guide for the Care and Use of Laboratory Animals, and approved by the Animal Care Committee of Beijing University of Chinese Medicine. The drug used in this study was the same batch as the previously published study [16]. The fingerprint spectrum was established by the high performance liquid chromatography method to control the quality of the QSG.…”

“…The fingerprint spectrum was established by the high performance liquid chromatography method to control the quality of the QSG. The results of the quality control of QSG were described in detail in our previous study [16].…”

“…QSG and fosinopril (Bristol-Myers Squibb, China) were dissolved in sterile saline. The rats in the QSG group were treated with QSG at a daily dose of 18.66 g/kg for 28 days as previous study [16]. The rats in the positive control group were treated with fosinopril at a daily dose of 1.2 mg/kg as previous study [16].…”

“…The rats in the QSG group were treated with QSG at a daily dose of 18.66 g/kg for 28 days as previous study [16]. The rats in the positive control group were treated with fosinopril at a daily dose of 1.2 mg/kg as previous study [16]. Rats in the sham group and model group were administered with normal saline (10 ml/kg/day).…”

“…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].…”