Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

Abstract

Application of the anticancer drug doxorubicin (DOX) is restricted due to its adverse, cardiotoxic side effects, which ultimately result in heart failure. Moreover, there are a limited number of chemical agents for the clinical prevention of DOX-induced cardiotoxicity. Based on the theories of traditional Chinese medicine (TCM) on chronic heart failure (CHF), Shenlijia (SLJ), a new TCM compound, has been developed to fulfill multiple functions, including improving cardiac function and inhibiting cardiac fibrosis. In the present study, the protective effects and molecular mechanisms of SLJ on DOX-induced CHF rats were investigated. The CHF rat model was induced by intraperitoneal injection of DOX for six weeks with the cumulative dose of 15 mg/kg. All rats were then randomly divided into the control, CHF, CHF + SLJ (3.0 g/kg per day), and CHF + captopril (3.8 mg/kg per day) groups and treated for further four weeks. Echocardiography and the assessment of hemodynamic parameters were performed to evaluate heart function. A protein chip was applied to identify proteins with diagnostic values that were differentially expressed following SLJ treatment. The data from these investigations showed that SLJ treatment significantly improved cardiac function by increasing the left ventricular ejection fraction, improving the hemodynamic index, and inhibiting interstitial fibrosis. Protein chip analysis revealed that SLJ upregulated MCP-1, MDC, neuropilin-2, TGF-β3, thrombospondin, TIE-2, EG-VEGF/PK1, and TIMP-1/2/3 expressions and downregulated that of MMP-13. In addition, immunohistochemistry and western blot results further confirmed that SLJ promoted TIMP-1/2/3 and inhibited MMP-13 expression. The results of the present study suggest that SLJ was effective against DOX-induced CHF rats and is related to the improvement of heart function and ultrastructure and the inhibition of myocardial fibrosis.

Biofabrication of advanced in vitro 3D models to study ischaemic and doxorubicin-induced myocardial damage

“…We reported an upregulation of Ccnd1 and Rarres1 following DOX treatment, consistent with previous studies [36,37]. Genes correlated with cardiac remodeling, such as Ace, Mmp13 and Ren1 were overexpressed in response to DOX treatment, typical of DOX-mediated myocardial damage [30,39,40]. We also observed that most of the apoptosis regulating genes are upregulated following DOX treatment compared to controls in both mCSs and hCSs, consistent with previous studies [30].…”

“…Ace, Mmp13 and Ren1 were similarly upregulated following DOX-mediated damaged. They all were upregulated in both mCSs and hCSs compared to control and were consistent with our I/R injury model and previous DOX mediated cardiac damage studies (table 2) [30,39,40].…”

Warming Yang Promoting Blood Circulation and Diuresis Alleviates Myocardial Damage by Inhibiting Collagen Fiber and Myocardial Fibrosis and Attenuating Mitochondria Signaling Pathway Mediated Apoptosis in Chronic Heart Failure Rats

“…However, some previous studies (Cui et al, 2017;Wang et al, 2019) showed that the left ventricular ejection fraction was less than 50%, indicating the successful modeling of heart failure. These findings are similar to those experimental heart failure models previously established (Bai et al, 2017;Wu et al, 2019;Sun et al, 2021;Wei et al, 2022;Xu et al, 2022;Suto et al, 2023). Furthermore, according to the design plan of this study, an echocardiogram test was performed after the construction of the CHF model, with the aim of screening the successfully modeled rats.…”

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy

“…Shenlijia (SLJ) can improve cardiac function and inhibit MF progression. It improves cardiac function and ultrastructure, and inhibits MF development in DOX-induced CHF rats by upregulating extracellular matrix-metalloproteinase inhibitor (TIMP) expression ( 76 ) ( Figure 2 ).…”