Qi Dan Li Xin pill improves chronic heart failure by regulating mTOR/p70S6k-mediated autophagy and inhibiting apoptosis

Abstract

Myocardial remodeling represents a key factor in chronic heart failure (CHF) development, and is characterized by chronic death of cardiomyocytes. Cardiac function changes may be attributed to inflammation, apoptosis and autophagy. This study assessed the effects of Qi Dan Li Xin Pill (QD) on heart function, inflammatory factors, autophagy and apoptosis in cardiac remodeling in CHF rats upon myocardial infarction (MI) induction.Male SD rats underwent a sham procedure or left anterior descending coronary artery (LADCA) ligation, causing MI. Twenty-eight days after modeling, the animals were treated daily with QD, valsartan and saline for 4 weeks. Echocardiography after 4 weeks of drug intervention revealed substantially improved left ventricular remodeling and cardiac function following QD treatment. As demonstrated by decreased IL-1β, IL-6 and TNF-α amounts, this treatment also inhibited the apoptotic process and protected the viability of the myocardium. These outcomes may be attributed to enhanced autophagy in cardiomyocytes, which further reduced pro-inflammatory and pro apoptotic effects. This process may be achieved by QD regulation of the mTOR/P70S6K signaling pathway, suggesting that the traditional Chinese medicine Qi Dan Li Xin pill is effective in heart protective treatment, and is worth further investigation.

Qiliqiangxin Modulates the Gut Microbiota and NLRP3 Inflammasome to Protect Against Ventricular Remodeling in Heart Failure

“…The beneficial effects of QL on cardiac hypertrophy, ventricular remodeling, and HF through multiple pathways have been widely reported ( Gao et al, 2018 ; Lu et al, 2020 ; Wang et al, 2017 ). Valsartan, an angiotensin II (ANG II) receptor blocker, exerts positive effects in improving chronic inflammation, promoting scar repair, maintaining cardiomyocyte integrity, alleviating ventricular remodeling, and thus preserving cardiac functions ( Shi et al, 2020 ). Further studies indicated that valsartan administration could affect the intestinal microbiota composition and SCFA generation and blunted the LPS-induced elevations of inflammatory cytokines ( Iwashita et al, 2013 ; Qi et al, 2021 ).…”

Programmed Cell Death: Complex Regulatory Networks in Cardiovascular Disease

“…mTOR is an important regulatory molecule that induces autophagy, and activating mTOR by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MARK) transduction can inhibit autophagy. In contrast, the negative regulation of mTOR by adenosine monophosphate-activated protein kinase (AMPK) and p53 signal transduction promotes autophagy (Dong et al, 2019;Shi et al, 2020). The formed mTOR complex is extensively linked to the downstream autophagy-related gene (ATG) family to construct the autophagosomes and ultimately complete the process of ubiquitin-like reactions.…”

“…Sciarretta S et al found that in ischemic stress, Rheb, as a GTP-binding protein, could inhibit autophagy by activating mTORC1, thereby aggravating post-ischemic infarct size (Sciarretta et al, 2012). During heart failure and aortic atherosclerosis, miR-212/132, laminar flow and Danqi pills regulated autophagy by modulating autophagyrelated pathways and molecules, affecting cardiac function (Supplementary Table S4) (Oka et al, 2012;Shi et al, 2020;Grootaert et al, 2015;Ucar et al, 2012;Yuan et al, 2020;Wang et al, 2021b). As mentioned before, autophagy restricted to an appropriate extent protects against ischemic injury via maintaining cardiomyocyte homeostasis, degrading organelles, or misfolding proteins that produce adenosine triphosphate (ATP).…”

Cellular and Molecular Mechanism of Traditional Chinese Medicine on Ventricular Remodeling

“…Autophagy can promote survival by inhibiting apoptosis under several different conditions, and sometimes lead to cell death by cooperating with apoptosis or as a supplement to apoptosis defects. Tong-Xin-Luo, Tong-Guan Capsules, and Qi-Dan-Li-Xin Pills can all play the role of anti-VR by anti-cardiomyocyte apoptosis and promoting cardiomyocyte autophagy (71)(72)(73). Rapamycin mechanical target is a key regulatory protein involved in protein production, cell growth/proliferation, autophagy, lysosomal function, and the metabolic pathway, and is considered to be the central regulator of cell growth.…”

“…It can also deacetylate p53 to inhibit apoptosis. Qi-Dan-Li-Xin Pill also promotes the autophagy of cardiomyocytes by down-regulating the mTOR/P70/S6K/4EBP1 pathway ( 73 ). Yang-Xin-Kang Tablets, prepared using Panax ginseng C.A.Mey .…”