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Cardiotoxicity of doxorubicin (DOX) has gained increasing attention in clinical application. Fuzhengkangfu (FZK) decoction, a traditional Chinese herbal formula of replenishing Qi strengthening spleen, has been used to treat various cardiovascular diseases. However, the chemical composition, the protective effects of FZK, and the underlying mechanisms are yet unclear. In this study, an high-performance liquid chromatography−mass spectrometry (HPLC−MS) analytical method was established for the structural identification of constituents in FZK extracts. Target prediction and enrichment analysis of the identified ingredients were performed. The cell viability was measured via (3-[4,5dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT) assay. The protective effects of FZK on cell survival, mitochondrial membrane potential, intracellular calcium homeostasis, and cell apoptosis were detected. The level of relevant proteins was measured by Western blot. The effect of FZK on the antitumor activity of DOX was evaluated in HeLa cells. A total of 42 major chemical constituents were identified in FZK extracts by HPLC−MS. A comprehensive target prediction of these constituents retrieved 46 pathways, of which several key pathways were related to mitochondrial dysfunction, including metabolic pathways and calcium signaling pathways. Furthermore, FZK ameliorated DOX-induced H9C2 cell apoptosis and increased the Bcl-2/Bax ratio. Also, it moderated the loss of mitochondrial membrane potential and reduced the intracellular calcium overload, which are the major targets of DOX-induced injury. These results confirmed that FZK ameliorates DOX-induced cardiotoxicity via antiapoptotic and mitochondrial protection but does not affect the antitumor activity of DOX.

Heart failure (HF) is the end stage of several cardiovascular diseases with high mortality worldwide; however, current chemical drugs have not beneficial effect on reducing its mortality rate. Due to its properties of multiple targets components with multiple targets, natural products derived from traditional Chinese medicine (TCM) have exerts unique effects on the amelioration of the clinical symptoms of HF, yet, TCM is not widely used in the clinic since the potential therapeutic targets have not been fully investigated. Therefore, in this review, we briefly summarized the pathophysiological mechanism of HF and reviewed the published clinical evaluations of TCM and natural products from Chinese herbs to treat HF. Then, the therapeutic potential and the underlying mechanisms by which the natural products from Chinese herb exert their protective effects were further summarized. We concluded from this review that natural products from Chinese herbs have been shown to be more effective in treating HF by targeting multiple signaling pathways, including anticardiac hypertrophy, antifibrotic, anti-inflammatory, antioxidative and antiapoptotic activities. However, the major limitations of these compounds is that there are a lack of large scale, multicenter, randomized and controlled clinical trials for their use in treatment of HF, and the toxic effects of natural products from Chinese herbs also needed further investigation. Despite these limitations, further clinical trials and experimental studies will provide a better understanding of the mechanism of natural products from Chinese herbs and promote their wide use to treat HF.

BackgroundCoronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them. Nevertheless, the molecular pathways underlying the pathogenic comorbidities for both traits remain poorly studied. We sought to identify common pathways and key driver genes by performing a comprehensive integrative analysis based on multi-omic datasets.MethodsBy performing a pathway-based analysis of GWAS summary data, we identified that lipoprotein metabolism process-related pathways were significantly associated with CAD risk. Based on LD score regression analysis of CAD-related SNPs, significant heritability enrichments were observed in the cardiovascular and digestive system, as well as in liver and gastrointestinal tissues, which are the main regulators for lipid level.ResultsWe found there existed significant genetic correlation between CAD and other lipid metabolism related traits (the smallest P value < 1 × 10− 16). A total of 13 genes (e.g., LPA, APOC1, APOE and SLC22A3) was found to be overlapped between CAD and plasma lipid levels. By using the data-driven approach that integrated transcriptome information, we discovered co-expression modules associated prominently with both CAD and plasma lipids. With the detailed topology information on gene-gene regulatory relationship, we illustrated that the identified hub genes played important roles in the pathogenesis of CAD and plasma lipid turbulence.ConclusionTogether, we identified the shared molecular mechanisms underlying the correlation between CAD and plasma lipid levels.