Abstract
Qingre Jiedu (QJ) recipe exerted significant cardioprotective efficacy against heart failure (HF), which is a growing health concern that continues to endanger patients' lives. To investigate the protective properties and mechanism of the QJ recipe, we established hydrogen peroxide (H2O2)-induced H9C2 cells and HF rats. The predicted targets and significant pathways of QJ against HF were collected and screened based on network pharmacology from key ingredients and validated by in vivo and in vitro experiments. The decoction of QJ (0.823 g/kg/day) was intragastrically administered for four weeks. QJ (400 μg/mL) was cultured with H2O2 stimulated in the H9C2 cells. A total of 31 effective active compounds were screened in QJ and covered 277 targets, of which 85 were shared with HF-related targets. In vivo, the QJ recipe remarkably protected heart function and reduced serum IL-1, IL-6, PIIINP, and CIV levels. Furthermore, QJ downregulated the key proteins mediating inflammatory responses (p-IKKα/β, p-NFκB, and IL-6) and cardiac fibrosis (STAT3 and MMP-9). In vitro, QJ protected the cardiomyocytes against H2O2-stimulated reactive oxygen species (ROS) production and upregulated PI3K and AKT expressions. Further experiments demonstrate that PI3K inhibitor LY294002 remarkably compromised the effects of QJ. In conclusion, our findings indicate that QJ could exert a cardioprotective effect and inhibit fibrosis and inflammation in HF rats via the PI3K-AKT signaling pathway.
Highlights
Despite recent advances in treating cardiovascular disorders, heart failure (HF) remains the leading cause of death worldwide, imposing a heavy social and economic burden [1]
Data Preparation. e components of Scrophularia ningpoensis Hemsl. [Scrophulariaceae] (Xuanshen) and Lonicera japonica unb. [Caprifoliaceae] (Jinyinhua) identified in the Qingre Jiedu (QJ) recipe were collected from TCMSP, and the potential targets of QJ ingredients were predicted with an analogous method applied in the BATMANTCM platform
Echocardiography data revealed that rats in the model group had significantly lower values of ejection fraction (EF) and fractional shortening (FS), while their diameters on left ventricular internal dimensiondiastole (LVID); s and LVID; d were longer than those in the sham group, revealing that the HF model was successfully induced
Summary
Despite recent advances in treating cardiovascular disorders, heart failure (HF) remains the leading cause of death worldwide, imposing a heavy social and economic burden [1]. Fibrosis and inflammation play a key part in response to HF pathological process [2]. There is an urgent need to decipher the mechanism of fibrosis and inflammation in HF and identify new therapeutic targets for HF treatment. IL-6 activates the PI3K-AKT pathway via its receptor (IL-6Rα) [5]. PI3K belongs to a conserved family of lipid kinases and is the primary regulator of AKT activation [6]. PI3K could phosphorylate IKK into active form and activate downstream target NF-κB to regulate inflammatory responses [7]. NF-κB is a key transcriptional factor that regulates the expressions of inflammation-related genes, such as TNF-α and IL-6 [8]. Cytokines are released, which exacerbate inflammation response and other remodeling markers in myocardial fibrosis (MFs), such as MMP-9 [9].
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