Cardioprotective Effect of Stem-Leaf Saponins From Panax notoginseng on Mice With Sleep Derivation by Inhibiting Abnormal Autophagy Through PI3K/Akt/mTOR Pathway.

Yin Cao,Mingrui Li,Zhengtao Wang,Hui Wu,Xiaojun Wu,Shengqi Chen,Wenjing Fan,Qinglin Li,Zunji Ke,Jinfeng Yuan,Yingbo Yang

doi:10.3389/fcvm.2021.694219

Abstract

Sleep deprivation (SD) may lead to serious myocardial injury in cardiovascular diseases. Saponins extracted from the roots of Panax notoginseng, a traditional Chinese medicine beneficial to blood circulation and hemostasis, are the main bioactive components exerting cardiovascular protection in the treatment of heart disorders, such as arrhythmia, ischemia and reperfusion injury, and cardiac hypertrophy. This study aimed to explore the protective effect of stem-leaf saponins from Panax notoginseng (SLSP) on myocardial injury in SD mice. SD was induced by a modified multi-platform method. Cardiac morphological changes were assessed by hematoxylin and eosin (H&E) staining. Heart rate and ejection fraction were detected by specific instruments. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of autophagy and apoptosis in heart tissue of SD mice. In vitro, rat H9c2 cells pretreated with rapamycin and the effect of SLSP were explored by acridine orange staining, transient transfection, flow cytometry, and Western blotting analysis. SLSP prevented myocardial injury, such as morphological damage, accumulation of autophagosomes in heart tissue, abnormal high heart rate, serum ANP, and serum LDH induced by SD. In addition, it reversed the expressions of proteins involved in the autophagy and apoptosis and activated PI3K/Akt/mTOR signaling pathway that is disturbed by SD. On H9c2 cells induced by rapamycin, SLSP could markedly resume the abnormal autophagy and apoptosis. Collectively, SLSP attenuated excessive autophagy and apoptosis in myocardial cells in heart tissue induced by SD, which might be acted through activating PI3K/Akt/mTOR signaling pathway.

Highlights

Sleep deprivation (SD) caused by undesirable lifestyle habits and sleep disorders, such as insomnia, obstructive sleep apnea, and neurological diseases, has become a worldwide health problem [1]
SD increased the heart rate of mice significantly compared with the control group, as well as the serum lactate dehydrogenase (LDH) and atrial natriuretic peptide (ANP) levels (Figures 2E,F, P = 0.00017 and P = 0.000036)
These results clearly demonstrated that stem-leaf saponins from Panax notoginseng (SLSP) could rescue the myocardial injury caused by SD

Summary

Introduction

Sleep deprivation (SD) caused by undesirable lifestyle habits and sleep disorders, such as insomnia, obstructive sleep apnea, and neurological diseases, has become a worldwide health problem [1]. It can increase catecholamine, coronary vasomotor tone, blood pressure, and heart rate, thereby disturbs the balance of oxygen supply and demand, resulting in excessive vasoconstriction, fibrosis, and cardiac remodeling in cardiac diseases [2]. Many reports revealed the close link or causality between the dysregulated autophagy and apoptosis in myocardial injury [17]. Drugs either activating or deactivating autophagy have both been demonstrated to alleviate myocardial injury [17], suggesting the beneficial effects of the recovery of aberrant autophagy on cardiac diseases

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Results

Conclusion