Effects of Shenfu Qiangxin Drink on H₂O₂‑induced oxidative stress, inflammation and apoptosis in neonatal rat cardiomyocytes and possible underlying mechanisms

Abstract

The aim of the present study was to investigate the effects of Shenfu Qiangxin Drink (SFQXD) on acute myocardial infarction (AMI) and identify the possible underlying mechanisms. Levels of reactive oxygen species (ROS) and inflammatory factors, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in the blood samples of patients with AMI were measured using commercially available kits by visible spectrophotometry after SFQXD administration. The contents of phosphorylated (p-) forkhead box O3a (FOXO3a) was examined using an ELISA kit. In addition, a hydrogen peroxide (H 2 O 2 )-induced myocardial injury model was established in vitro using neonatal rat cardiomyocytes. Following treatment with SFQXD, the levels of intracellular ROS, cell apoptosis, oxidative stressand inflammation-related markers were measured using commercially available kits by visible spectrophotometry. Additionally, western blot analysis was used to measure the expression of sirtuin-4 (SIRT4), p-FOXO3a, acetylated FOXO3a (ace-FOXO3a) and apoptosis-related genes (Bcl-2, Bax, BIM and cleaved caspase-3). Subsequently, to investigate the possible underlying regulatory mechanisms, SIRT4 expression was silenced by transfection with small hairpin RNA against SIRT4, following which changes in the extent of oxidative stress, inflammation and apoptosis were assessed. The levels of ROS and interleukin (IL)-1β were found to be significantly reduced, whilst FOXO3a phosphorylation was markedly increased following administration with SFQXD. In vitro, SFQXD dose-dependently inhibited H 2 O 2 -induced oxidative stress, inflammation and apoptosis in neonatal rat cardiomyocytes. In addition, FOXO3a phosphorylation was markedly upregulated whilst FOXO3a acetylation was downregulated following treatment of H 2 O 2 -induced primary neonatal cardiomyocytes with SFQXD. SIRT4 knockdown also markedly reversed the effects of SFQXD on oxidative stress, inflammation and apoptosis in neonatal rat cardiomyocytes. In conclusion, these findings demonstrated that SFQXD may alleviate oxidative stress-induced myocardial injury by potentially regulating SIRT4/FOXO3a signaling, suggesting that SFQXD may be of clinical value for the treatment of AMI.

The recent advance and prospect of natural source compounds for the treatment of heart failure

“…Shenfu Qiangxin pill is composed of Panax ginseng , Aconitum carmichaeli , Morus alba , Grifola umbellata , Lepidium apetalum and Rheum palmatum , which is used to tonifying qi and warm yang, and strengthen heart and promote diuresis [ 220 ]. On the basis of conventional Western medicine treatment, Shenfu Qiangxin pill can further improve the cardiac function of HF patients through inhibiting the RAAS system, regulating the levels of ANP and BNP, and reverse ventricular remodeling.…”

Network pharmacology and molecular docking analysis on Shenfu Qiangxin indicate mTOR is a potential target to treat heart failure

“…SFQX is composed of six Chinese herbal extracts: Ginseng (Renshen, RS), Aconiti Lateralis Radix Praeparata (Fuzi, FZ), Mori Cortex (Sangbaipi, SBP), Polyporus Umbellatus (Zhuling, ZL), Descurainiae Semen (Tinglizi, TLZ) and Radix Rhei Et Rhizome (Dahuang, DH). It is reported that SFQX may alleviate oxidative stress-induced myocardial injury by regulating SIRT4/FOXO3a signaling in animal and cell studies [ 8 ]. However, the detail mechanisms of SFQX in treating HF remain unclear.…”