Shengxian decoction decreases doxorubicin‑induced cardiac apoptosis by regulating the TREM1/NF‑κB signaling pathway

Abstract

Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX-induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK-8 and flow cytometry. Triggering receptors expressed on myeloid cells 1 (TREM1), cleaved caspase-3, survivin and NF-κBp65 expression levels were measured by reverse transcription-quantitative PCR and/or western blotting. A total of 30 adult male Sprague-Dawley rats were randomly allocated into five groups (n=6 each); control group receiving 0.9% saline, 1 DOX group receiving 2.5 mg/kg of DOX and 3 DOX + SXT groups, receiving a DOX dose equivalent to the DOX-only group and either 0.4, 0.8 or 1.6 g/kg of SXT. It was found that DOX increased apoptosis and NF-κB activation of H9c2 cells by increasing TREM1 expression and that SXT inhibited apoptosis and NF-κB activation of H9c2 cells induced by DOX or Trem1 overexpression. SXT also significantly reversed DOX-induced cardiotoxicity in rats. The results suggested that the protective effects of SXT against DOX-induced apoptosis may be attributed to its downregulation of TREM1.

Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity

“…Over the last decades, several mechanisms were incriminated by scientists to be responsible for this cardiotoxicity, including increased generation of reactive oxygen species (ROS) with significant detriment of the antioxidant defense mechanisms in cardiac tissues [5]. In addition, the direct effects of doxorubicin on nuclear factor kappa-B (NF-κB) expression with modulation of the balance between the pro-inflammatory and the anti-inflammatory cytokines were proven to be responsible for the toxic effects of doxorubicin on cardiomyocytes [6]. Moreover, downregulation of neuregulin-1, which is considered as a key element in the cell survival pathways in cardiac tissues, by doxorubicin, was proposed as an important contributing mechanism [7].…”

Chemical and Biological Evidence of the Efficacy of Shengxian Decoction for Treating Human Lung Adenocarcinoma

“…Increasing evidence suggests that traditional Chinese medicine is beneficial for improving the clinical outcomes of LUAD patients (10). SXT has been widely used for treating diseases related to immune and cardiovascular diseases in China for a long time (6)(7)(8). Although the therapeutic use of SXT for cancer treatment has not been extensively studied, its constituent herbs have been shown to be useful for the treatment of cancers, including LUAD (10,12,15,16,33).…”

“…(5). SXT can be used to treat experimental autoimmune myasthenia gravis (6), cardiomyocyte injuries (7), and chronic heart failure (8). The anti-cancer activity of SXT has rarely been reported; however, the individual constituents of SXT have been shown to attenuate cancer growth.…”

Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis

“…Furthermore, the rats were given ECH (50 or 100 mg/kg) by gavage for 2 weeks. To monitor cardiac function, an echocardiogram was performed, and hemodynamic variables were assessed ( 20 ). After treatment completion, the animals were anesthetized with 2% sodium pentobarbital (50 mg/kg) (B005, Jiancheng Bioengineering Institute) and sacrificed by cervical dislocation, and their hearts were removed.…”