Abstract
Qishen granule (QSG) is a frequently prescribed traditional Chinese medicine formula, which improves heart function in patients with heart failure (HF). However, the cardioprotective mechanisms of QSG have not been fully understood. The current study aimed to elucidate whether the effect of QSG is mediated by ameliorating cytoplasmic calcium (Ca2+) overload in cardiomyocytes. The HF rat model was induced by left anterior descending (LAD) artery ligation surgery. Rats were randomly divided into sham, model, QSG-low dosage (QSG-L) treatment, QSG-high dosage (QSG-H) treatment, and positive drug (diltiazem) treatment groups. 28 days after surgery, cardiac functions were assessed by echocardiography. Levels of norepinephrine (NE) and angiotensin II (AngII) in the plasma were evaluated. Expressions of critical proteins in the calcium signaling pathway, including cell membrane calcium channel CaV1.2, sarcoendoplasmic reticulum ATPase 2a (SERCA2a), calcium/calmodulin-dependent protein kinase type II (CaMKII), and protein phosphatase calcineurin (CaN), were measured by Western blotting (WB) and immunohistochemistry (IHC). Echocardiography showed that left ventricular ejection fraction (EF) and fractional shortening (FS) value significantly decreased in the model group compared to the sham group, and illustrating heart function was severely impaired. Furthermore, levels of NE and AngII in the plasma were dramatically increased. Expressions of CaV1.2, CaMKII, and CaN in the cardiomyocytes were upregulated, and expressions of SERCA2a were downregulated in the model group. After treatment with QSG, both EF and FS values were increased. QSG significantly reduced levels of NE and AngII in the plasma. In particular, QSG prevented cytoplasmic Ca2+ overload by downregulating expression of CaV1.2 and upregulating expression of SERCA2a. Meanwhile, expressions of CaMKII and CaN were inhibited by QSG treatment. In conclusion, QSG could effectively promote heart function in HF rats by restoring cardiac Ca2+ homeostasis. These findings revealed novel therapeutic mechanisms of QSG and provided potential targets in the treatment of HF.
Highlights
Heart failure remains one of the major threats to people’s health, great progress has been made in the understanding of HF pathophysiology and advances in its therapeutic strategies [1]
Scrophularia, Radix Aconiti Lateralis Preparata, and Radix Glycyrrhizae. is formulae is widely manufactured in China in accordance with the China Pharmacopoeia standard of quality control. e fingerprint of QSG was analyzed by highperformance liquid chromatography (HPLC)-IT-TOF-MS, and the typical chromatograms were reported as we described before [20]
The extracted QSG was enriched by 4 times. e fingerprint spectrum was further established by the highperformance liquid chromatography (HPLC) method in our previous studies [20, 22]. e major components are formononetin, tanshinone IIA, tanshinone I, cryptotanshinone, and harpagoside [23]. e Chinese herbs were identified by Professor Jian Ni, School of Chinese Materia Medica, Beijing University of Chinese Medicine. e voucher specimens (Voucher numbers: HQ-2016-007; DQ-2016-008; JYH-2016009; XS-2016-010; FZ-2016-011; and GC-2016-012) were submitted to Department of Chinese Medicine Teaching and Research, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine
Summary
Heart failure remains one of the major threats to people’s health, great progress has been made in the understanding of HF pathophysiology and advances in its therapeutic strategies [1]. It poses the entire medical community a tremendous challenge to further explore HF pathogenesis and the treatment approaches. Free calcium ions are mainly distributed in the extracellular fluid such as blood and intracellular organelles such as sarcoplasmic reticulum. It is the cytosolic Ca2+ concentration that directly determines the myocardial contractility. Activated CaV1.2 or reduced expression of SERCA2a leads to accumulation of Ca2+ in the cytosol, which prevents relaxation and further impairs contractility due to depletion of the Ca2+ available for release during systole [10, 11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Evidence-Based Complementary and Alternative Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
