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.